Nghiên cứu quy trình chế tạo và đánh giá hiệu quả tác động của hệ nano đa chức năng (polymerdrugFe3O4folate) lên tế bào ung thư

BỘ GIÁO DỤC VÀ ĐÀO TẠO VIỆN HÀN LÂM KHOA HỌC VÀ CÔNG NGHỆ VIỆT NAM HỌC VIỆN KHOA HỌC VÀ CÔNG NGHỆ - LÊ THỊ THU HƢƠNG NGHIÊN CỨU CHẾ TẠO VÀ ĐÁNH GIÁ HIỆU QUẢ TÁC ĐỘNG CỦA HỆ NANO ĐA CHỨC NĂNG (POLYMER-DRUG- Fe3O4-FOLATE) LÊN TẾ BÀO UNG THƢ LUẬN ÁN TIẾN SỸ KHOA HỌC VẬT LIỆU HÀ NỘI – 2018 BỘ GIÁO DỤC VÀ ĐÀO TẠO VIỆN HÀN LÂM KHOA HỌC VÀ CÔNG NGHỆ VIỆT NA HỌC VIỆN KHOA HỌC VÀ CÔNG NGHỆ - LÊ THỊ THU HƢƠNG NGHIÊN CỨU CHẾ TẠO VÀ ĐÁNH GIÁ HIỆU QUẢ TÁC ĐỘNG CỦA HỆ NANO ĐA CHỨC NĂNG (POLYMER-DRUG- Fe3O4-FOLATE) LÊN TẾ BÀO UNG THƢ LUẬN ÁN TIẾN SỸ KHOA HỌC VẬT LIỆU Chuyên ngành: Vật liệu điện tử Mã số: 9440123 Ngƣời hƣớng dẫn khoa học: TS Hà Phƣơng Thƣ GS.TSKH Nguyễn Xuân Phúc Hà Nội – 2018 LỜI CAM ĐOAN Tôi xin cam Ďoan Ďây công trình nghiên cứu riêng tơi dƣới hƣớng dẫn TS Hà Phƣơng Thƣ GS.TSKH Nguyễn Xuân Phúc khơng trùng lặp với cơng trình khoa học khác Các số liệu kết nghiên cứu nêu luận án trung thực, Ďƣợc Ďồng tác giả cho phép sử dụng chƣa Ďƣợc sử dụng Ďể bảo vệ học vị nào, chƣa Ďƣợc cơng bố cơng trình khác Hà Nội, tháng năm 2018 Tác giả luận án Lê Thị Thu Hƣơng LỜI CẢM ƠN Tôi xin bày tỏ lòng biết ơn chân thành sâu sắc Ďến tập thể giáo viên hƣớng dẫn, TS Hà Phƣơng Thƣ GS TSKH Nguyễn Xuân Phúc Ďã tận tình hƣớng dẫn, hỗ trợ Ďịnh hƣớng cho suốt thời gian thực luận án Đặc biệt, xin chân thành cảm ơn hỗ trợ kinh phí từ Ďề tài KHCN mã số 106-YS.06-2015.14 (HPT) Ďề án 911 Xin chân thành cảm ơn Ban lãnh Ďạo Khoa Khoa học vật liệu lƣợng Học viện Khoa học Cơng nghệ Phòng Vật liệu Nano Y sinh, Phòng thí nghiệm trọng Ďiểm - Viện Khoa học Vật liệu, Viện Hàn làm Khoa học Công nghệ Việt Nam Ďã tạo Ďiều kiện thuận lợi sở vật chất cho tơi suốt q trình thí nghiệm Ďóng góp ý kiến chun mơn suốt q trình thực bảo vệ Luận án Tôi xin chân thành cảm ơn Ban Giám Ďốc, BCN Khoa Môi trƣờng tập thể Bộ môn Hố học, Học viện Nơng nghiệp Việt Nam, Ďã tạo Ďiều kiện giúp Ďỡ tơi q trình cơng tác Ďể tơi hồn thành luận án Xin cảm ơn Ban lãnh Ďạo phận Đào tạo Viện Khoa học Vật liệu Ďã hỗ trợ tơi hồn thành học phần luận án thủ tục cần thiết khác trình thực luận án Cuối xin bày tỏ lời cảm ơn sâu sắc Ďến gia Ďình, Ďã ln chia sẻ, Ďộng viên tinh thần nguồn cổ vũ, giúp Ďỡ vƣợt qua khó khăn suốt q trình thực Luận án Hà nội, ngày tháng năm 2018 Nghiên cứu sinh Lê Thị Thu Hƣơng i MỤC LỤC DANH MỤC CÁC KÍ HIỆU, CÁC CHỮ VIẾT TẮT .v DANH MỤC CÁC BẢNG viii DANH MỤC CÁC HÌNH VẼ, ĐỒ THỊ .x MỞ ĐẦU .1 CHƢƠNG 1: TỔNG QUAN .4 1.1 Khái quát hệ vật liệu nano y sinh 1.1.1 Cấu trúc hệ nano y sinh 1.1.2 Các chức y sinh hệ .6 1.2 Phƣơng pháp tổng hợp hạt nano Fe3O4 1.2.1 Phƣơng pháp Ďồng kết tủa 1.2.2 Phƣơng pháp thuỷ nhiệt 1.2.3 Phƣơng pháp phân huỷ nhiệt .9 1.2.4 Sử dụng kĩ thuật vi sóng tổng hợp Fe3O4 10 1.3 Tính chất ứng dụng hạt nano Fe3O4 y sinh học 11 1.3.1 Một số tính chất từ hạt nano oxit sắt từ Fe3O4 11 1.3.2 Mang thuốc hƣớng Ďích 13 1.3.3 Nhiệt trị phóng thích thuốc dựa hiệu ứng Ďốt nóng cảm ứng từ 15 1.3.4 Tăng cƣờng Ďộ tƣơng phản ảnh cộng hƣởng từ hạt nhân .18 1.3.5 Hệ nano Ďa chức .20 1.4 Vấn Ďề hạt nano oxit sắt từ cho ứng dụng y sinh 23 1.5 Chức hoá bề mặt hạt Fe3O4 .25 1.5.1 Bền hoá hạt nano Fe3O4 polime tổng hợp 25 1.5.2 Bền hoá hạt nano Fe3O4 polime tự nhiên .26 1.5.3 Kết hợp thuốc chống ung thƣ 29 1.5.4 Yếu tố hƣớng Ďích folate 31 Kết luận chƣơng .33 CHƢƠNG 2: VẬT LIỆU VÀ PHƢƠNG PHÁP NGHIÊN CỨU 34 2.1 Tổng hợp vật liệu .34 2.1.1 Nguyên vật liệu .34 2.1.2 Tổng hợp hạt nano oxit sắt từ phƣơng pháp Ďồng kết tủa 34 ii 2.1.3 Tổng hợp hạt nano Fe3O4 theo phƣơng pháp Ďồng kết tủa sử dụng kĩ thuật vi sóng 34 2.1.4 Bọc hạt nano Fe3O4 polime sinh học 36 2.1.5 Mang thuốc Curcumin Doxorubicin lên hệ 36 2.1.6 Gắn yếu tố hƣớng Ďích folate 37 2.1.7 Kết hợp chấm lƣợng tử CdTe 38 2.2 Các phƣơng pháp Ďặc trƣng tính chất hệ 39 2.2.1 Nhiễu xạ tia X 39 2.2.2 Phổ hấp thụ hồng ngoại 40 2.2.3 Phổ UV-Vis huỳnh quang 40 2.2.4 Phân tích nhiệt 41 2.2.5 Hiển vi Ďiện tử 42 2.2.6 Các phƣơng pháp Ďo từ 42 2.2.7 Phổ tán xạ ánh sáng Ďộng 42 2.2.8 Đốt nóng cảm ứng từ .43 2.2.9 Xác Ďịnh hiệu suất dung lƣợng mang thuốc .43 2.2.10 Q trình giải phóng thuốc in vitro .43 2.2.11 Giải phóng thuốc Ďốt nóng cảm ứng 44 2.3 Thử nghiệm sinh học 44 2.3.1 Thử nghiệm khả nhập bào Ďộc tính tế bào FOC FOCF 44 2.3.2 Xác Ďịnh phân bố hệ nano mang curcumin quan chuột 45 2.3.3 Xác Ďịnh Ďộc tính tế bào FAD, FADF, FAQ FADQ 46 2.3.4 Thí nghiệm xác Ďịnh khả Ďiều trị in vivo hệ Ďa chức mang Dox kết hợp với Ďốt nóng cảm ứng từ 46 2.4 Phƣơng pháp xử lí số liệu 48 CHƢƠNG 3: HẠT NANO Fe3O4 BỌC BẰNG OCMCS MANG CURCUMIN 49 3.1 Tổng hợp hạt nano Fe3O4 49 3.1.1 Hạt nano Fe3O4 tổng hợp theo phƣơng pháp Ďồng kết tủa thông thƣờng 49 3.1.2 Hạt nano Fe3O4 tổng hợp theo phƣơng pháp Ďồng kết tủa có hỗ trợ vi sóng 50 iii 3.2 Ảnh hƣởng hàm lƣợng curcumin lên tính chất hệ mang Curcumin (FOC1-FOC5) 55 3.3 Hệ nano mang curcumin (FOC) mang Curcumin gắn folate (FOCF) 57 3.3.1 Phổ hồng ngoại 57 3.3.2 Phổ huỳnh quang .58 3.3.3 Ảnh hiển vi Ďiện tử quét (FeSEM) 59 3.3.4 Phân tích nhiệt 60 3.3.5 Giản Ďồ nhiễu xạ tia X Ďƣờng cong từ trễ 61 3.3.6 Kết Ďốt nóng cảm ứng từ 62 3.3.7 Độ bền FOC FOCF môi trƣờng sinh lí .64 3.3.8 Q trình giải phóng thuốc in vitro 64 3.3.9 Độc tính tế bào 66 3.3.10 Phân bố sinh học 68 Kết luận chƣơng 3: 71 CHƢƠNG 4: HẠT NANO Fe3O4 BỌC BẰNG ALGINATE MANG DOXORUBICIN .72 4.1 Ảnh hƣởng nồng Ďộ alginate Ďến khả mang Dox tính chất hệ nano 72 4.1.1 Phổ hồng ngoại phổ huỳnh quang 72 4.1.2 Dung lƣợng thuốc hiệu suất mang thuốc 73 4.1.3 Phân bố kích thƣớc ảnh TEM .74 4.1.4 Giản Ďồ nhiễu xạ tia X Ďƣờng cong từ trễ 76 4.1.5 Kết Ďốt nóng cảm ứng từ 77 4.1.6 Phân tích nhiệt 80 4.1.7 Q trình giải phóng thuốc in vitro 81 4.1.8 Độc tính tế bào 83 4.2 Ảnh hƣởng lõi Fe3O4 tổng hợp vi sóng tới tính chất hệ nano .86 4.2.1 Một số Ďặc trƣng vật liệu kết Ďốt nóng cảm ứng từ .86 4.2.2 Độc tính tế bào 88 4.3 Hệ nano mang Dox gắn folate (FADF) CdTe (FADQ) 88 4.3.1 Phổ hồng ngoại 89 iv 4.3.2 Phổ huỳnh quang .89 4.3.3 Kích thƣớc hạt Zeta 91 4.3.4 Giản Ďồ XRD 91 4.3.5 Tính chất từ khả Ďốt nóng cảm ứng 92 4.3.6 Quá trình giải phóng Dox thụ Ďộng chủ Ďộng nhờ hiệu ứng Ďốt nóng cảm ứng .93 4.3.7 Độc tính tế bào 96 4.3.8 Độ bền FAD, FADF FADQ mơi trƣờng sinh lí 99 4.3.9 Kết thử nghiệm in vivo 100 Kết luận chƣơng 105 KẾT LUẬN .107 NHỮNG ĐÓNG GÓP MỚI CỦA LUẬN ÁN .109 DANH MỤC CÁC CƠNG TRÌNH SỬ DỤNG TRONG LUẬN ÁN 110 Tài liệu tham khảo 112 v DANH MỤC CÁC KÍ HIỆU, CÁC CHỮ VIẾT TẮT Alg: alginate CS% (% cell survival): số tế bào sống sót (%) Cur: Curcumin DLS (dynamic light scattering): tán xạ ánh sáng Ďộng Dox: Doxorubicin Drug: thuốc DrTGA: tốc Ďộ khối lƣợng DTA (differential thermal gravity analysis): phân tích nhiệt vi sai EE (encapsulating efficiency): hiệu suất mang thuốc EPR (enhanced permeability and retention effect): Hiệu ứng tăng tính thấm thời gian lƣu FA: mẫu Fe3O4 tổng hợp vi sóng bọc alginate nồng Ďộ mg/ml FA2D-FA10D: mẫu Fe3O4 bọc alginate nồng Ďộ khác mang doxorubicin FA2-FA10: mẫu Fe3O4 bọc alginate nồng Ďộ khác FAD: mẫu Fe3O4 tổng hợp vi sóng bọc alginate nồng Ďộ mg/ml mang doxorubicin FADF: mẫu Fe3O4 tổng hợp vi sóng bọc alginate nồng Ďộ mg/ml mang doxorubicin gắn folate FADQ: mẫu Fe3O4 tổng hợp vi sóng bọc alginate nồng Ďộ mg/ml mang doxorubicin gắn CdTe FeSEM (field emission Scanning electron mỉctoscopy): hiển vi Ďiện tử quét phát xạ trƣờng FL: tế bào ung thƣ vân tim FOC (hoặc FOC3): Fe3O4 bọc OCMCS mang curcumin với lƣợng curcumin tham gia phản ứng 60 mg FOC1-FOC5: Fe3O4 bọc OCMCS mang curcumin với lƣợng curcumin tham gia phản ứng khác (từ 20-100 mg) vi FOCF: Fe3O4 bọc OCMCS mang curcumin gắn folate (với lƣợng curcumin tham gia phản ứng 60 mg) Fol: folate FR (folate receptor): thụ thể folate H: cƣờng Ďộ từ trƣờng Hc: lực kháng từ Hela: tế bào ung thƣ cổ tử cung Hep-G2: tế bào ung thƣ gan HT-29: tế bào ung thƣ ruột kết IC50 (inhibition concentration): nồng Ďộ ức chế 50% số tế bào ILP (intrinsic loss power): công suất tổn hao nội LC (loading content): dung lƣợng thuốc LU-1: tế bào ung thƣ phổi tế bào nhỏ M (magnetization): từ Ďộ Ms (satutation magnetization): từ Ďộ bão hòa Mr (magnetic remanance): từ dƣ M1-M11: mẫu Fe3O4 tổng hợp vi sóng MIH (magnetic inductive heating): Ďốt nóng cảm ứng từ MNP (magnetic nanoparticles): hạt nano từ MRI (magnetic resonance image): ảnh cộng hƣởng từ OCMCS: O- Cacboxylmetyl chitosan QD (quantum dots): chấm lƣợng tử SAR (specific absorption rate): tốc Ďộ hấp thụ riêng SD (standard deviation): Ďộ lệch chuẩn SLP (specific loss power): công suất tổn hao riêng TEM (transmission electron microscopy): hiển vi Ďiện tử truyền qua TGA (thermal gravity analysis): phân tích nhiệt Vero: tế bào biểu mơ thận khỉ 110 DANH MỤC CÁC CƠNG TRÌNH SỬ DỤNG TRONG LUẬN ÁN Le Thi Thu Huong, Ung Thi Dieu Thuy, Le Mai Huong, Tran Thi Hong Ha, Pham Hong Nam, Ha Phuong Thu “Introduction of labeling CdTe quantum dots to magnetic nano drug delivery system: a novel approach for cancer theranostic.” The 8th International Workshop on Advanced Materials Science and Nanotechnology, Ha Long, 2016 Huong Le Thi Thu, Nguyen Hoai Nam, Do Hai Doan, Hoang Thi My Nhung, Bui Thuc Quang, Pham Hong Nam, Phan Quoc Thong, Nguyen Xuan Phuc, and Ha Phuong Thu “Folate Attached, Curcumin Loaded Fe3O4 Nanoparticles: A Novel Multifunctional Drug Delivery System for Cancer Treatment.” Materials Chemistry and Physics 172 (2016) 98–104 Ha Phuong Thu, Le Thi Thu Huong, Hoang Thi My Nhung, Nguyen Dac Tu, Nguyen Thi Tham, Ha Thi Minh Thi, Pham Thi Bich Hanh, Tran Thi Minh Nguyet, Nguyen Thi Quy, Pham Hong Nam, Tran Dai Lam, Nguyen Xuan Phuc, and Duong Tuan Quang “Fe3O4/o-Carboxymethyl Chitosan/Curcuminbased Nanodrug System for Chemotherapy and Fluorescence Imaging in HT29 Cancer Cell Line” Chemistry Letters 40, 11 (2011) Thi Thu Huong Le, Thuc Quang Bui, Thi Minh Thi Ha, Mai Huong Le, Hong Nam Pham, Phuong Thu Ha “Optimizing the Alginate Coating Layer of Doxorubicin Loaded Iron Oxide Nanoparticles for Cancer Hyperthermia and Chemotherapy.” Journal of Materials Science 53 (2018) 13826-13842 DANH MỤC CÁC CƠNG TRÌNH CĨ LIÊN QUAN ĐẾN HƢỚNG NGHIÊN CỨU CỦA LUẬN ÁN Duong Thi Thuy, Thanh Son Le, Thi Thu Huong Tran, Trung Kien Nguyen, Cuong Tu Ho, Trong Hien Dao, Thi Phuong Quynh Le, Hoai Chau Nguyen, Dinh Kim Dang, Thi Thu Huong Le and Phuong Thu Ha “Inhibition effect of engineered silver nanoparticles to bloom forming cyanobacteria.” Advances in Natural Sciences: Nanoscience and Nanotechnology (2016) 035018, Phan Quoc Thong, Mai Huong Le, Thi Thu Huong Le, Thi Hong Ha Tran, Phuc Nguyen Xuan, and Phuong Thu Ha “Characteristics and Cytotoxicity of 111 Folate-Modified Curcumin-Loaded PLA-PEG Micellar Nano Systems with Various PLA:PEG Ratios.” International Journal of Pharmaceutics 507 (2016) 32–40 Hong Nam Pham, Thi Ha Giang Pham, Dac Tu Nguyen, Quoc Thong Phan, Thi Thu Huong Le, Phuong Thu Ha, Hung Manh Do, Thi My Nhung Hoang and Xuan Phuc Nguyen “Magnetic inductive heating of organs of mouse models treated by copolymer coated Fe3O4 nanoparticles.” Advances in Natural Sciences: Nanoscience and Nanotechnology (2017) 025013 Hai Doan Do, Hao Le Thi, Thu Huong Le Thi, Hoai Nam Nguyen, Van Khanh Bui, My Nhung Hoang Thi and Phuong Thu Ha “Folate-modified, curcumin and paclitaxel co-loaded PLA-TPGS nanoparticles: preparation, optimization and in vitro cytotoxicity assays”, Advances in Natural Sciences: Nanoscience and Nanotechnology 9(2018) 025004 112 Tài liệu tham khảo Srinivasan M, Rajabi M, Mousa SA (2015) Multifunctional Nanomaterials and Their Applications in Drug Delivery and Cancer Therapy Nanomaterials 5:1690–1703 Misra R, Sahoo SK (2011) Co-formulation of doxorubicin and curcumin in poly (D, L-lactide-co-glycolide) nanoparticles suppress the development of multi drug resistance in K562 cells Molecular PharmaceuticsPharm 8:852–866 Ganta S, Amiji M (2009) Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells Molecular Pharmaceutics 6:928–939 Ahn D, Lee J, Park S, et al (2014) Doxorubicin-Loaded Alginate ‑ g ‑ Poly( N ‑ isopropylacrylamide) Micelles for Cancer Imaging and Therapy ACS Applied Materials & Interfaces 6:22069–77 Frey NA, Peng S, Cheng K, Sun S (2009) Magnetic nanoparticles: Synthesis, functionalization, and applications in bioimaging and magnetic energy storage Chemical Society Reviews 38:2532–2542 Sun C, Lee JSH, Zhang M (2008) Magnetic nanoparticles in MR imaging and drug delivery Advanced Drug Delivery Reviews 60:1252–1265 Reddy LH, Arias JL, Nicolas J, Couvreur P (2012) Magnetic nanoparticles: Design and Characerization,Toxicity and Biocompatibility,Pharmaceutical and Biomedical Applications Chemical Reviews 112:5818–5878 Balasubramanian S, Ravindran Girija A, Nagaoka Y, et al (2014) Curcumin and 5-Fluorouracil-loaded, folate- and transferrin-decorated polymeric magnetic nanoformulation: A synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia International Journal of Nanomedicine 9:437–459 Sun M, Sun B, Liu Y, et al (2016) Dual-Color Fluorescence Imaging of Magnetic Nanoparticles in Live Cancer Cells Using Conjugated Polymer Probes Scientific Reports 6:22368 10 Yu MK, Jeong YY, Park J, et al (2008) Drug-Loaded Superparamagnetic Iron Oxide Nanoparticles for Combined Cancer Imaging and Therapy In Vivo ** Evolution 1–5 11 Ke JH, Lin JJ, Carey JR, et al (2010) A specific tumor-targeting magnetofluorescent nanoprobe for dual-modality molecular imaging Biomaterials 31:1707–1715 12 Bower KC, Gardner KH, Miller CM, Kong L (2001) In situ colloidal MnO2 deposition and ozonation of 2, 4-dinitrotoluene Environmental engineering science 18:259 13 Thinh NN, Hanh PTB, Ha LTT, et al (2013) Magnetic chitosan nanoparticles for removal of Cr(VI) from aqueous solution Materials Science and Engineering C 33:1214–1218 14 Oanh VTK (2016) Nghiên cứu chế tạo chất lỏng từ hạt nano Fe3O4 chất lượng cao định hướng cho số ứng dụng y sinh Luận án tiến sĩ, Học viện Khoa học Công nghệ, Viện Hàn lâm Khoa học Công nghệ Việt Nam 15 Phong PT, Nam PH, Manh DH, Lee I-J (2017) Mn0.5Zn0.5Fe2O4 nanoparticles with high intrinsic loss power for hyperthermia therapy Journal of 113 Magnetism and Magnetic Materials 433:76–83 16 Linh PH (2014) Nghiên cứu chế tạo chất lỏng từ hạt nano Fe3O4 ứng dụng diệt tế bào ung thư Luận án tiến sĩ, Viện Khoa học vật liệu, Viện Hàn lâm khoa học công nghệ Việt Nam 17 Shi J, Kantoff PW, Wooster R, Farokhzad OC (2017) Cancer nanomedicine: Progress, challenges and opportunities Nature Reviews Cancer 17:20–37 18 Nune SK, Gunda P, Thallapally PK, et al (2009) Nanoparticles for biomedical imaging Expert Opinion in Drug Delivery 6:1175–1194 19 Leuschner C, Kumar C (2005) Nanofabrication towards biomedical applications : Techniques, tools, applications, and impact In: Nanoparticles for Cancer Drug Delivery pp 289–326 20 Karimi Z, Karimi L, Shokrollahi H (2013) Nano-magnetic particles used in biomedicine : Core and coating materials Materials Science & Engineering C 33:2465–2475 21 Bao G, Mitragotri S, Tong S (2013) Multifunctional Nanoparticles for Drug Delivery and Molecular Imaging Annual Review of biomedical engineering 15:253–82 22 Wang G-P, Song E-Q, Xie H-Y, et al (2005) Biofunctionalization of fluorescent-magnetic-bifunctional nanospheres and their applications Chemical communications (Cambridge, England) 0:4276–4278 23 Liang X, Jia X, Cao L, et al (2010) Microemulsion Synthesis and Characterization of Nano-Fe3O4 Particles and Fe3O4 Nanocrystalline Journal of Dispersion Science and Technology 31:1043–1049 24 Tung DK, Manh DH, Phong LTH, et al (2016) Iron Nanoparticles Fabricated by High-Energy Ball Milling for Magnetic Hyperthermia Journal of Electronic Materials 45:2644–2650 25 Lemine OM, Omri K, Zhang B, et al (2012) Sol–gel synthesis of 8nm magnetite (Fe3O4) nanoparticles and their magnetic properties Superlattices and Microstructures 52:793–799 26 Agiotis L, Theodorakos I, Samothrakitis S, et al (2016) Magnetic manipulation of superparamagnetic nanoparticles in a microfluidic system for drug delivery applications Journal of Magnetism and Magnetic Materials 401:956–964 27 Laurent S, Forge D, Port M, et al (2010) Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications (vol 108, pg 2064, 2008) Chemical Reviews 110:2574 28 Qiao RR, Yang CH, Gao MY (2009) Superparamagnetic iron oxide nanoparticles: from preparations to in vivo MRI applications Journal of Materials Chemistry 19:6274–6293 29 Davies KJ, Wells S, Charles SW (1993) The effect of temperature and oleate adsorption on the growth of maghemite particles Journal of Magnetism and Magnetic Materials 122:24–28 30 López-López MT, Durán JDG, Delgado a V., González-Caballero F (2005) Stability and magnetic characterization of oleate-covered magnetite ferrofluids in different nonpolar carriers Journal of Colloid and Interface Science 291:144– 151 114 31 Lan Q, Liu C, Yang F, et al (2007) Synthesis of bilayer oleic acid-coated Fe3O4 nanoparticles and their application in pH-responsive Pickering emulsions Journal of Colloid and Interface Science 310:260–269 32 Debrassi A, Bürger C, Antonio C, et al (2011) Synthesis , characterization and in vitro drug release of magnetic N -benzyl- O -carboxymethylchitosan nanoparticles loaded with indomethacin Acta Biomaterialia 7:3078–3085 33 Castelló J, Gallardo M, Busquets MA, Estelrich J (2015) Chitosan (or alginate)-coated iron oxide nanoparticles: A comparative study Colloids and Surfaces A: Physicochemical and Engineering Aspects 468:151–158 34 Blanco-Andujar C, Ortega D, Southern P, et al (2015) High performance multi-core iron oxide nanoparticles for magnetic hyperthermia: microwave synthesis, and the role of core-to-core interactions Nanoscale 7:1768–75 35 Yazdani F, Seddigh M (2016) Magnetite nanoparticles synthesized by coprecipitation method : The effects of various iron anions on specifications Materials Chemistry and Physics 184:318–324 36 Phu ND, Phong PC, Chau N, et al (2009) Arsenic removal from water by magnetic Fe1−xCoxFe2O and Fe1−yNiyFe2O4 nanoparticles Journal of Experimental Nanoscience 4:253–258 37 Tuan MA, Hai NH (2009) DNA enrichment by functionalized magnetic nanoparticles for on-site and fast detection of virus in biomedical application Journal of Physics: Conference Series 187:012059 38 Nguyễn HĐ, Trần MD, Trần TD (2007) Chế tạo nghiên cứu tính chất từ hạt Nanô Fe3O4 ứng dụng y sinh học Tạp chí Khoa học ĐHQGHN, Khoa học Tự nhiên Công nghệ 23:231–237 39 Devkota J, Mai TTT, Stojak K, et al (2014) Synthesis, inductive heating, and magnetoimpedance-based detection of multifunctional Fe3O4 nanoconjugates Sensors and Actuators, B: Chemical 190:715–722 40 Linh PH, Thach P Van, Tuan NA, et al (2009) Magnetic fluid based on Fe O nanoparticles: Preparation and hyperthermia application Journal of Physics: Conference Series 187:012069 41 Nguyen XP, Tran DL, Ha PT, et al (2012) Iron oxide-based conjugates for cancer theragnostics Advances in Natural Sciences: Nanoscience and Nanotechnology 3:033001 42 Thong PQ, Thu HPT, Huong LTT, et al (2016) Structure and properties of Fe3O4 nanoparticles coated by PLA-PEG copolymer with and without loading of curcumin Journal of Science and Technology 54:268–276 43 Daou TJ, Pourroy G, Bégin-Colin S, et al (2006) Hydrothermal synthesis of monodisperse magnetite nanoparticles Chemistry of Materials 18:4399–4404 44 Mizutani N, Iwasaki T, Watano S, et al (2008) Effect of ferrous/ferric ions molar ratio on reaction mechanism for hydrothermal synthesis of magnetite nanoparticles Bulletin of Materials Science 31:713–717 45 Vƣơng TKO, Trần ĐL, Đỗ HM, et al (2015) Nghiên cứu chế tạo chất lỏng từ Fe3O4 phương pháp thuỷ nhiệt cho định hướng ứng dụng y sinh Tạp chí Hóa học 53:275–278 46 Sun S, Zeng H (2002) Size-controlled synthesis of magnetite nanoparticles Journal of the American Chemical Society 124:8204–8205 115 47 Park J, An K, Hwang Y, et al (2004) Ultra-large-scale syntheses of monodisperse nanocrystals Nature Materials 3:891–895 48 Oanh VTK, Lam TD, Thu VT, et al (2016) A Novel Route for Preparing Highly Stable Fe3O4 Fluid with Poly(Acrylic Acid) as Phase Transfer Ligand Journal of Electronic Materials 45:4010–4017 49 Vuong TKO, Tran DL, Le TL, et al (2015) Synthesis of high-magnetization and monodisperse Fe3O4 nanoparticles via thermal decomposition Materials Chemistry and Physics 163:537–544 50 Ling D, Hyeon T (2013) Chemical design of biocompatible iron oxide nanoparticles for medical applications Small 9:1450–1466 51 Zhang T, Ge J, Hu Y, Yin Y (2007) A general approach for transferring hydrophobic nanocrystals into water Nano Letters 7:3203–3207 52 Li C, Wei Y, Liivat A, et al (2013) Microwave-solvothermal synthesis of Fe3O4 magnetic nanoparticles Materials Letters 107:23–26 53 Kappe CO (2004) Controlled Microwave Heating in Modern Organic Angewandte Chemie-International Edition 43:6250–6284 54 Dahl JA, Maddux BLS, Hutchison JE (2007) Toward greener nanosynthesis Chemical Reviews 107:2228–2269 55 Hong RY, Pan TT, Li HZ (2006) Microwave synthesis of magnetic Fe3O4 nanoparticles used as a precursor of nanocomposites and ferrofluids Journal of Magnetism and Magnetic Materials 303:60–68 56 Rizzuti A, Dassisti M, Mastrorilli P, et al (2015) Shape-control by microwave-assisted hydrothermal method for the synthesis of magnetite nanoparticles using organic additives Journal of Nanoparticle Research 17:408 57 Osborne EA, Atkins TM, Gilbert DA, et al (2012) Rapid microwave-assisted synthesis of dextran-coated iron oxide nanoparticles for magnetic resonance imaging Nanotechnology 23:215602 58 Wang WW, Zhu YJ, Ruan ML (2007) Microwave-assisted synthesis and magnetic property of magnetite and hematite nanoparticles Journal of Nanoparticle Research 9:419–426 59 Teja AS, Koh P-Y (2009) Synthesis, properties, and applications of magnetic iron oxide nanoparticles Progress in Crystal Growth and Characterization of Materials 55:22–45 60 Cullity BD, Graham CD (2008) Domains and the Magnetization Process In: Introduction to Magnetic Materials John Wiley & Sons, Inc., pp 275–333 61 Lu AH, Salabas EL, Schüth F (2007) Magnetic nanoparticles: Synthesis, protection, functionalization, and application Angewandte Chemie International Edition 46:1222–1244 62 Estelrich J, Escribano E, Queralt J, Busquets MA (2015) Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery International Journal of Molecular Sciences 16:8070–8101 63 Krishnan KM, Pakhomov AB, Bao Y, et al (2006) Nanomagnetism and spin electronics: Materials, microstructure and novel properties Journal of Materials Science 41:793–815 64 Ghasemzadeh G, Momenpour M, Omidi F, et al (2014) Applications of nanomaterials in water treatment and environmental remediation Frontiers of 116 Environmental Science and Engineering 8:471–482 65 Mansoori G a, Bastami TR, Ahmadpour a, Eshaghi Z (2008) Chapter Environmental Application of Nanotechnology Annual Review of Nano Research, 2:1–73 66 Allia P, Barrera G, Tiberto P, et al (2014) Fe3O4 nanoparticles and nanocomposites with potential application in biomedicine and in communication technologies: Nanoparticle aggregation, interaction, and effective magnetic anisotropy Journal of Applied Physics 116:113903 67 Franzreb M, Siemann-Herzberg M, Hobley TJ, Thomas ORT (2006) Protein purification using magnetic adsorbent particles Applied microbiology and biotechnology 70:505–516 68 Kettering M, Winter J, Zeisberger M, et al (2007) Magnetic nanoparticles as bimodal tools in magnetically induced labelling and magnetic heating of tumour cells: an in vitro study Nanotechnology 18:175101 69 Chertok B, David AE, Yang VC (2011) Brain tumor targeting of magnetic nanoparticles for potential drug delivery: Effect of administration route and magnetic field topography Journal of Controlled Release 155:393–399 70 Chorny M, Fishbein I, Yellen BB, et al (2010) Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields Proceedings of the National Academy of Sciences of the United States of America 107:8346–8351 71 Al-Jamal KT, Bai J, Wang JTW, et al (2016) Magnetic Drug Targeting: Preclinical in Vivo Studies, Mathematical Modeling, and Extrapolation to Humans Nano Letters 16:5652–5660 72 Zhang L, Yu F, Cole AJ, et al (2009) Gum arabic-coated magnetic nanoparticles for potential application in simultaneous magnetic targeting and tumor imaging Aaps J 11:693–699 73 Jordan A, Scholz R, Wust P, et al (1999) Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles Journal of Magnetism and Magnetic Materials 201:413–419 74 Jordan A, Scholz R, Wust P, et al (1999) Endocytosis of dextran and silancoated magnetite nanoparticles and the effect of intracellular hyperthermia on human mammary carcinoma cells in vitro Journal of Magnetism and Magnetic Materials 194:185–196 75 Kulkarni VM, Bodas D, Dhoble D, et al (2016) Radio-frequency triggered heating and drug release using doxorubicin-loaded LSMO nanoparticles for bimodal treatment of breast cancer Colloids and Surfaces B: Biointerfaces 145:878–890 76 Hergt R, Dutz S, Müller R, Zeisberger M (2006) Magnetic particle hyperthermia: nanoparticle magnetism and materials development for cancer therapy Journal of Physics: Condensed Matter 18:S2919–S2934 77 Hervault A, Thanh NTK (2014) Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer Nanoscale 6:11553–11573 78 Grüttner C, Müller K, Teller J, Westphal F (2013) Synthesis and functionalisation of magnetic nanoparticles for hyperthermia applications 117 International Journal of Hyperthermia 29:777–789 79 Deatsch AE, Evans B a (2014) Heating efficiency in magnetic nanoparticle hyperthermia Journal of Magnetism and Magnetic Materials 354:163–172 80 Salas G, Veintemillas-Verdaguer S, Morales MDP (2013) Relationship between physico-chemical properties of magnetic fluids and their heating capacity International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 29:768–76 81 Kallumadil M, Tada M, Nakagawa T, et al (2009) Suitability of commercial colloids for magnetic hyperthermia Journal of Magnetism and Magnetic Materials 321:1509–1513 82 Zhao DL, Wang XX, Zeng XW, et al (2009) Preparation and inductive heating property of Fe3O4-chitosan composite nanoparticles in an AC magnetic field for localized hyperthermia Journal of Alloys and Compounds 477:739–743 83 Hayashi K, Ono K, Suzuki H, et al (2010) High-frequency, magnetic-fieldresponsive drug release from magnetic nanoparticle/organic hybrid based on hyperthermic effect ACS Applied Materials and Interfaces 2:1903–1911 84 Gilchrist RK, Shorey WD, Hanselman RC, et al (1957) Selective inductive heating of lymph nodes Annals of Surgery 146:596–606 85 Gaitas A, Kim G (2015) Inductive heating kills cells that contribute to plaque : a proof-of-concept PeerJ 3:e929 86 Hilger I (2013) In vivo applications of magnetic nanoparticle hyperthermia Int J Hyperthermia 29:1464–5157 87 Thiesen B, Jordan A (2008) Clinical applications of magnetic nanoparticles for hyperthermia International Journal of Hyperthermia 24:467–474 88 Babincová M, Čičmanec P, Altanerová V, et al (2002) AC-magnetic field controlled drug release from magnetoliposomes: Design of a method for sitespecific chemotherapy Bioelectrochemistry 55:17–19 89 N’Guyen TTT, Duong HTT, Basuki J, et al (2013) Functional iron oxide magnetic nanoparticles with hyperthermia-induced drug release ability by using a combination of orthogonal click reactions Angewandte Chemie - International Edition 52:14152–14156 90 Na H Bin, Song IC, Hyeon T (2009) Inorganic nanoparticles for MRI contrast agents Advanced Materials 21:2133–2148 91 Rogers WJ, Basu P (2005) Factors regulating macrophage endocytosis of nanoparticles: Implications for targeted magnetic resonance plaque imaging Atherosclerosis 178:67–73 92 Jun YW, Lee JH, Cheon J (2008) Chemical design of nanoparticle probes for high-performance magnetic resonance imaging Angewandte Chemie International Edition 47:5122–5135 93 Clements TW, Sarsons C, Platnich  CM, et al (2016) Maltol-Functionalized Fe O Nanoparticles as T Magnetic Resonance Imaging Contrast Agents ChemistrySelect 1:1602–1606 94 Khalkhali M, Sadighian S, Rostamizadeh K, et al (2015) Synthesis and characterization of dextran coated magnetite nanoparticles for diagnostics and therapy Bioimpacts 5:141–150 118 95 Jiang QL, Zheng SW, Hong RY, et al (2014) Folic acid-conjugated Fe3O4 magnetic nanoparticles for hyperthermia and MRI in vitro and in vivo Applied Surface Science 307:224–233 96 Smolensky ED, Park HYE, Berquó TS, Pierre VC (2011) Surface functionalization of magnetic iron oxide nanoparticles for MRI applications effect of anchoring group and ligand exchange protocol Contrast Media and Molecular Imaging 6:189–199 97 Beg MS, Mohapatra J, Pradhan L, et al (2017) Porous Fe3O4-SiO2 coreshell nanorods as high-performance MRI contrast agent and drug delivery vehicle Journal of Magnetism and Magnetic Materials 428:340–347 98 Fan C, Gao W, Chen Z, et al (2011) Tumor selectivity of stealth multifunctionalized superparamagnetic iron oxide nanoparticles International Journal of Pharmaceutics 404:180–190 99 Hao H, Ma Q, He F, Yao P (2014) Doxorubicin and Fe O loaded albumin nanoparticles with folic acid modified dextran surface for tumor diagnosis and therapy J Mater Chem B 2:7978–7987 100 Bhattacharya D, Das M, Mishra D, et al (2011) Folate receptor targeted, carboxymethyl chitosan functionalized iron oxide nanoparticles: a novel ultradispersed nanoconjugates for bimodal imaging Nanoscale 3:1653–1662 101 Portnoy E, Polyak B, Inbar D, et al (2016) Tracking inflammation in the epileptic rat brain by bi-functional fluorescent and magnetic nanoparticles Nanomedicine: Nanotechnology, Biology, and Medicine 12:1335–1345 102 Cho HS, Dong Z, Pauletti GM, et al (2010) Fluorescent, superparamagnetic nanospheres for drug storage, targeting, and imaging: A multifunctional nanocarrier system for cancer diagnosis and treatment ACS Nano 4:5398–5404 103 Singh SP (2011) Multifunctional magnetic quantum dots for cancer theranostics Journal of Biomedical Nanotechnology 7:95–97 104 Kamat M, El-Boubbou K, Zhu DC, et al (2010) Hyaluronic acid immobilized magnetic nanoparticles for active targeting and imaging of macrophages Bioconjugate Chemistry 21:2128–2135 105 Gupta a, Gupta M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications Biomaterials 26:3995–4021 106 Wilhelm C, Gazeau F, Roger J, et al (2002) Interaction of anionic superparamagnetic nanoparticles with cells: Kinetic analyses of membrane adsorption and subsequent internalization Langmuir 18:8148–8155 107 Wilhelm C, Billotey C, Roger J, et al (2003) Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating 24:1001–1011 108 Maeda H, Bharate GY, Daruwalla J (2009) Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect European Journal of Pharmaceutics and Biopharmaceutics 71:409–419 109 Danhier F, Feron O, Préat V (2010) To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery Journal of Controlled Release 148:135–146 110 Majewski P, Thierry B (2007) Functionalized Magnetite Nanoparticles Synthesis,Properties,and Bio-Applications Critical Reviews in Solid State and 119 Materials Sciences 32:203–215 111 Chan LW, Lee HY, Heng PWS (2006) Mechanisms of external and internal gelation and their impact on the functions of alginate as a coat and delivery system Carbohydrate Polymers 63:176–187 112 Ningthoujam RS, Vatsa RK (2011) Heating tumors to Death using Functionalized Fe3O4 Magnetic Nanoparticles BARC Newsletter 18:18–23 113 Chen F-H, Zhang L-M, Chen Q-T, et al (2010) Synthesis of a novel magnetic drug delivery system composed of doxorubicin-conjugated Fe3O4 nanoparticle cores and a PEG-functionalized porous silica shell Chemical communications (Cambridge, England) 46:8633–8635 114 Pérez A, Mijangos C, Hernández R (2014) Preparation of hybrid Fe3O4/Poly(lactic-co-glycolic acid) (PLGA) particles by emulsion and evaporation method Optimization of the experimental parameters Macromolecular Symposia 335:62–69 115 Akbarzadeh A, Mikaeili H, Zarghami N, et al (2012) Preparation and in vitro evaluation of doxorubicin-loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymers International Journal of Nanomedicine 7:511– 526 116 Shi Y (2006) Superparamagnetic nanoparticles for magnetic resonance imaging (MRI) diagnosis Master thesis, The University ofAdelaide 117 Maia J, Evangelista MB, Gil H, Ferreira L (2014) Dextran-based materials for biomedical applications Carbohydrate Applications in Medicine 661:31–53 118 Varallyay P, Nesbit G, Muldoon LL, et al (2002) Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors AJNR American journal of neuroradiology 23:510–519 119 Rinaudo M (2006) Chitin and chitosan: Properties and applications Progress in Polymer Science 31:603–632 120 Anitha a., Maya S, Deepa N, et al (2011) Efficient water soluble Ocarboxymethyl chitosan nanocarrier for the delivery of curcumin to cancer cells Carbohydrate Polymers 83:452–461 121 Chen XG, Park HJ (2003) Chemical characteristics of O-carboxymethyl chitosans related to the preparation conditions Carbohydrate Polymers 53:355– 359 122 Jayakumar R, Prabaharan M, Nair S V., et al (2010) Novel carboxymethyl derivatives of chitin and chitosan materials and their biomedical applications Progress in Materials Science 55:675–709 123 Rahimi Z, Zinatizadeh AA, Zinadini S (2014) Preparation and characterization of a high antibiofouling ultrafiltration PES membrane using OCMCS-Fe O for application in MBR treating wastewater Journal of Applied Research in Water & Wastewater 1:13–17 124 Huang Y, Zhou Z, Liang J, et al (2015) Preparation , characterisation and in vitro cytotoxicity studies of chelerythrine-loaded magnetic Fe O @ Ocarboxymethylchitosan nanoparticles Journal of Experimental Nanoscience 10:483–498 125 Zhu A, Yuan L, Jin W, et al (2009) Polysaccharide surface modified Fe3O4 120 nanoparticles for camptothecin loading and release Acta Biomaterialia 5:1489– 1498 126 Li J, Jiang C, Lang X, et al (2016) Multilayer sodium alginate beads with porous core containing chitosan based nanoparticles for oral delivery of anticancer drug International Journal of Biological Macromolecules 85:1–8 127 Ma H, Qi X, Maitani Y, Nagai T (2007) Preparation and characterization of superparamagnetic iron oxide nanoparticles stabilized by alginate International Journal of Pharmaceutics 333:177–186 128 Segale L, Giovannelli L, Mannina P, Pattarino F (2016) Calcium Alginate and Calcium Alginate-Chitosan Beads Containing Celecoxib Solubilized in a Self-Emulsifying Phase Hindawi Publishing Corporation Scientific 2016: 129 Ma H, Qi X, Maitani Y, Nagai T (2007) Preparation and characterization of superparamagnetic iron oxide nanoparticles stabilized by alginate International Journal of Pharmaceutics 333:177–186 130 Araújo CC, Leon LL (2001) Biological activities of Curcuma longa L Memórias Instituto Oswaldo Cruz 96:723–8 131 Liang G, Shao L, Wang Y, et al (2009) Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents Bioorganic and Medicinal Chemistry 17:2623–2631 132 Tran LD, Hoang NMT, Mai TT, et al (2010) Nanosized magnetofluorescent Fe3O4-curcumin conjugate for multimodal monitoring and drug targeting Colloids and Surfaces A: Physicochemical and Engineering Aspects 371:104– 112 133 Li L, Braiteh FS, Kurzrock R (2005) Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis Cancer 104:1322–1331 134 Sou K, Inenaga S, Takeoka S, Tsuchida E (2008) Loading of curcumin into macrophages using lipid-based nanoparticles International Journal of Pharmaceutics 352:287–293 135 Yallapu MM, Dobberpuhl MR, Maher DM, et al (2012) Design of curcumin loaded cellulose nanoparticles for prostate cancer Current drug metabolism 13:120–8 136 Yallapu MM, Gupta BK, Jaggi M, Chauhan SC (2010) Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells Journal of colloid and interface science 351:19–29 137 Anand P, Nair HB, Sung B, et al (2010) Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo Biochemical pharmacology 79:330–338 138 Mancarella S, Greco V, Baldassarre F, et al (2015) Polymer-Coated Magnetic Nanoparticles for Curcumin Delivery to Cancer Cells Macromolecular Bioscience 15:1365–1374 139 Cheng KK, Chan PS, Fan S, et al (2015) Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer’s disease mice using magnetic resonance imaging (MRI) Biomaterials 44:155–172 140 Longhi A, Ferrari S, Bacci G, Specchia S (2007) Long-term follow-up of 121 patients with doxorubicin-induced cardiac toxicity after chemotherapy for osteosarcoma Anti-Cancer Drugs 18:737–44 141 Cheng Y, Yu S, Zhen X, et al (2012) Alginic acid nanoparticles prepared through counterion complexation method as a drug delivery system ACS Applied Materials and Interfaces 4:5325–5332 142 Kayal S, Ramanujan R V (2010) Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery Materials Science & Engineering C 30:484–490 143 Unsoy G, Khodadust R, Yalcin S, et al (2014) Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery European Journal of Pharmaceutical Sciences 62:243–250 144 Baghbani F, Moztarzadeh F, Mohandesi JA, et al (2016) Formulation design, preparation and characterization of multifunctional alginate stabilized nanodroplets International Journal of Biological Macromolecules 89:550–558 145 Yang L, Cao Z, Sajja HK, et al (2008) Development of receptor targeted magnetic iron oxide nanoparticles for efficient drug delivery and tumor imaging Journal of Biomedical Nanotechnology 4:439–449 146 Rana S, Shetake NG, Barick KC, et al (2016) Folic acid conjugated Fe3O4 magnetic nanoparticles for targeted delivery of doxorubicin Dalton Trans 45:17401–17408 147 Vasconcelos IB, Silva TG Da, Militão GCG, et al (2012) Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8 RSC Advances 2:9437 148 Jia Y, Yuan M, Yuan H, et al (2012) Co-encapsulation of magnetic Fe3O4 nanoparticles and doxorubicin into biodegradable PLGA nanocarriers for intratumoral drug delivery International Journal of Nanomedicine 7:1697–1708 149 Conniot J, Silva JM, Fernandes JG, et al (2014) Cancer immunotherapy: nanodelivery approaches for immune cell targeting and tracking Frontiers in chemistry 2:105 150 Bahrami B, Mohammadnia-Afrouzi M, Bakhshaei P, et al (2015) Folateconjugated nanoparticles as a potent therapeutic approach in targeted cancer therapy Tumor Biology 36:5727–5742 151 Ha PT, Nguyen HN, Do HD, et al (2016) Targeted drug delivery nanosystems based on copolymer poly (lactide)-tocopheryl polyethylene glycol succinate for cancer treatment Advances in Natural Sciences: Nanoscience and Nanotechnology 7:15001 152 Shen JM, Tang WJ, Zhang XL, et al (2012) A novel carboxymethyl chitosanbased folate/Fe 3O 4/CdTe nanoparticle for targeted drug delivery and cell imaging Carbohydrate Polymers 88:239–249 153 Li X, Tian X, Zhang J, et al (2011) In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel International journal of nanomedicine 6:1167–1184 154 Maeng JH, Lee D-H, Jung KH, et al (2010) Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer Biomaterials 31:4995–5006 155 Huong LTT, Nam NH, Doan DH, et al (2016) Folate attached, curcumin 122 loaded Fe3O4 nanoparticles: A novel multifunctional drug delivery system for cancer treatment Materials Chemistry and Physics 172:98–104 156 Shi X, Du Y, Yang J, et al (2006) Effect of degree of substitution and molecular weight of carboxymethyl chitosan nanoparticles on doxorubicin delivery Journal of Applied Polymer Science 100:4689–4696 157 Janes KA, Fresneau MP, Marazuela A, Fabra A (2001) Chitosan nanoparticles as delivery systems for doxorubicin Journal of Controlled Release 73:255–267 158 Guo H, Lai Q, Wang W, et al (2013) Functional alginate nanoparticles for efficient intracellular release of doxorubicin and hepatoma carcinoma cell targeting therapy International Journal of Pharmaceutics 451:1–11 159 Gao C, Tang F, Gong G, et al (2017) Glutathione-responsive nanoparticles from a sodium alginate derivative for selective release of doxorubicin in tumor cells Journal of Materials Chemistry B 5:2337–2346 160 Jingou J, Danjun W, Li L, et al (2012) Preparation, Evaluation, andIn VitroRelease of Folic Acid ConjugatedO-Carboxymethyl Chitosan Nanoparticles Loaded with Methotrexate Journal of Applied Polymer Science 125:E208–E215 161 Zhen Li, Hui Chen, Haobo Bao, and Mingyuan Gao* (2004) One-Pot Reaction to Synthesize Water-Soluble Magnetite Nanocrystals Chemistry of Materials 16:1391–1393 162 Li Y-S, Church JS, Woodhead AL (2012) Infrared and Raman spectroscopic studies on iron oxide magnetic nano-particles and their surface modifications Journal of Magnetism and Magnetic Materials 324:1543–1550 163 Casillas PEG, Gonzalez C a R, Pérez C a M (2009) Infrared Spectroscopy of Functionalized Magnetic Nanoparticles In: Infrared Spectroscopy pp 405–420 164 Aliahmad M, Nasiri Moghaddam N (2013) Synthesis of maghemite (γFe2O3) nanoparticles by thermal-decomposition of magnetite (Fe3O4) nanoparticles Materials Science-Poland 31:264–268 165 Lee H, Lee E, Kim DK, et al (2006) Antibiofouling Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles as Potential Magnetic Resonance Contrast Agents for in Vivo Cancer Imaging Antibiofouling Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles as Potential Magnetic Resonance Co Journal of the American Chemical Society 128:7383–7389 166 Jespersen N (2006) Chapter General principles of spectroscopy and spectroscopic analysis Comprehensive Analytical Chemistry 47:111–155 167 Sauer M, Hofkens J, Enderlein J (2011) Basic principles of Fluorescence spectroscopy In: Handbook of Fluorescence Spectroscopy and Imaging pp 1–30 168 Redfern JP, Coats AP (1963) Thermogravimetric Analysis - A review Analyst 88:906 169 Laurent S, Forge D, Port M, et al (2008) Magnetic iron oxide nanoparticles: Synthesis, stabilization, vectorization, physicochemical characterizations and biological applications Chemical Reviews 108:2064–2110 170 Jeffrey DC, Anil KP (2011) Chapter 6: Zeta potential measurement In: Characterization of Nanoparticles Intended for Drug DeliveryScientia Pharmaceutica pp 63–70 171 Likhitwitayawuid K, Angerhofer CK, Cordell GA, et al (1993) Cytotoxic and 123 Antimalarial Bisbenzylisoquinolme Alkaloids from Stephania erecta Journal of Natural Products 56:30–38 172 Skehan P, Storeng R, Scudiero D, et al (1990) New colorimetric cytotoxicity assay for anticancer-drug screening Journal of the National Cancer Institute 82:1107–1112 173 North-holland M, Materials M, Branch L, et al (1990) Physico-chemical regularities of obtaining highly dispersed magnetite y the method of chemical condensation Journal of Magnetism and Magnetic Materials 85:7–10 174 Fu R, Wang W, Han R, Chen K (2008) Preparation and characterization of ??-Fe2O3/ZnO composite particles Materials Letters 62:4066–4068 175 Kunwar A, Barik A, Pandey R, Priyadarsini KI (2006) Transport of liposomal and albumin loaded curcumin to living cells: An absorption and fluorescence spectroscopic study Biochimica et Biophysica Acta (BBA) General Subjects 1760:1513–1520 176 Cui J, Yu B, Zhao Y, et al (2009) Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems International Journal of Pharmaceutics 371:148–155 177 Sahu A, Kasoju N, Bora U (2008) Fluorescence study of the curcumin-casein micelle complexation and its application as a drug nanocarrier to cancer cells Biomacromolecules 9:2905–2912 178 Li H, Sun S, Yap JQ, et al (2016) 0.9% Saline Is Neither Normal Nor Physiological Journal of Zhejiang University-SCIENCE B 17:181–187 179 Zeinali S, Nasirimoghaddam S, Sabbaghi S (2016) Investigation of the Synthesis of Chitosan Coated Iron Oxide Nanoparticles under Different Experimental Conditions Int J Nanosci Nanotechnol, 12:183–190 180 Barick KC, Ekta E, Gawali SL, et al (2016) Pluronic stabilized Fe O magnetic nanoparticles for intracellular delivery of curcumin RSC Advances 6:98674–98681 181 Roxana Cristina Popescu, Ecaterina Andronescu AMG (2014) In vivo evaluation of Fe3O4 nanoparticles Romanian Journal of Morphology & Embriology 55:1013–1018 182 Goldin A, Ortega LG (1949) The Effect of Folic-Acid Derivatives on Sarcoma 180 Cancer 2:57–64 183 Wang G, Su X, Yang S, et al (2012) The double-effect mechanism between Fe3O4 nanoparticles and MSA-capped CdTe QDs Journal of Luminescence 132:2505–2511 184 Neuberger T, Schöpf B, Hofmann H, et al (2005) Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system Journal of Magnetism and Magnetic Materials 293:483– 496 185 Chouly C, Pouliquen D, Lucet I, et al (1996) Development of superparamagnetic nanoparticles for MRI: effect of particle size, charge and surface nature on biodistribution Journal of microencapsulation 13:245–255 186 Li Z, Kawashita M, Araki N, et al (2010) Magnetite nanoparticles with high heating efficiencies for application in the hyperthermia of cancer Materials Science and Engineering C 30:990–996 124 187 Singh AK, Srivastava ON, Singh K (2017) Shape and Size-Dependent Magnetic Properties of Fe3O4 Nanoparticles Synthesized Using Piperidine Nanoscale Research Letters 12:298 188 Rahmawati R, Permana MG, Harison B, et al (2017) Optimization of Frequency and Stirring Rate for Synthesis of Magnetite (Fe3O4) Nanoparticles by Using Coprecipitation- Ultrasonic Irradiation Methods Procedia Engineering 170:55–59 189 Piđeiro-Redondo Y, Bobre-López M, Pardiđas-Blanco I, et al (2011) The influence of colloidal parameters on the specific power absorption of PAAcoated magnetite nanoparticles Nanoscale research letters 6:383 190 Hervault A, Dunn AE, Lim M, et al (2016) Doxorubicin loaded dual pHand thermo-responsive magnetic nanocarrier for combined magnetic hyperthermia and targeted controlled drug delivery applications Nanoscale 8:21–24 191 Lima E, De Biasi E, Mansilla MV, et al (2013) Heat generation in agglomerated ferrite nanoparticles in an alternating magnetic field Journal of Physics D: Applied Physics 46:045002 192 Chin SF, Iyer KS, Saunders M, et al (2009) Encapsulation and sustained release of curcumin using superparamagnetic silica reservoirs Chemistry - A European Journal 15:5661–5665 193 Brulé S, Levy M, Wilhelm C, et al (2011) Doxorubicin release triggered by alginate embedded magnetic nanoheaters: A combined therapy Advanced Materials 23:787–790 194 Xu XQ, Shen H, Xu JR, et al (2006) The colloidal stability and core-shell structure of magnetite nanoparticles coated with alginate Applied Surface Science 253:2158–2164 195 Gao W, Zheng Y, Wang R, et al (2016) A smart, phase transitional and injectable DOX/PLGA-Fe implant for magnetic-hyperthermia-induced synergistic tumor eradication Acta Biomaterialia 29:298–306 196 Parker N, Turk MJ, Westrick E, et al (2005) Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay Analytical Biochemistry 338:284–293 197 Yang C-L, Chen J-P, Wei K-C, et al (2017) Release of Doxorubicin by a Folate-Grafted, Chitosan-Coated Magnetic Nanoparticle Nanomaterials 7:85 ...BỘ GIÁO DỤC VÀ ĐÀO TẠO VIỆN HÀN LÂM KHOA HỌC VÀ CÔNG NGHỆ VIỆT NA HỌC VIỆN KHOA HỌC VÀ CÔNG NGHỆ - LÊ THỊ THU HƢƠNG NGHIÊN CỨU CHẾ TẠO VÀ ĐÁNH GIÁ HIỆU QUẢ TÁC ĐỘNG CỦA HỆ NANO ĐA. .. Ďƣợc nghiên cứu hạn chế Trên sở phân tích kể trên, chúng tơi thực luận án Nghiên cứu chế tạo đánh giá hiệu tác động hệ nano đa chức (polymer-drugFe3O4-folate) lên tế bào ung thƣ” Mục tiêu nghiên. .. quang, dung lƣợng mang thuốc, Ďộ bền, khả phân tán hệ nano Ďa chức Ďã chế tạo 3 - Xác Ďịnh khả ức chế dòng tế bào ung thƣ in vitro - Xác Ďịnh hiệu Ďiều trị ung thƣ chuột hệ nano Ďa chức Ý nghĩa