ghiên cứu điều chỉnh cấu trúc và biến tính bề mặt vật liệu nano silica cấu trúc xốp rỗng cho ứng dụng phân phối thuốc điều trị ung thư.ghiên cứu điều chỉnh cấu trúc và biến tính bề mặt vật liệu nano silica cấu trúc xốp rỗng cho ứng dụng phân phối thuốc điều trị ung thư.ghiên cứu điều chỉnh cấu trúc và biến tính bề mặt vật liệu nano silica cấu trúc xốp rỗng cho ứng dụng phân phối thuốc điều trị ung thư.ghiên cứu điều chỉnh cấu trúc và biến tính bề mặt vật liệu nano silica cấu trúc xốp rỗng cho ứng dụng phân phối thuốc điều trị ung thư.ghiên cứu điều chỉnh cấu trúc và biến tính bề mặt vật liệu nano silica cấu trúc xốp rỗng cho ứng dụng phân phối thuốc điều trị ung thư.ghiên cứu điều chỉnh cấu trúc và biến tính bề mặt vật liệu nano silica cấu trúc xốp rỗng cho ứng dụng phân phối thuốc điều trị ung thư.ghiên cứu điều chỉnh cấu trúc và biến tính bề mặt vật liệu nano silica cấu trúc xốp rỗng cho ứng dụng phân phối thuốc điều trị ung thư.ghiên cứu điều chỉnh cấu trúc và biến tính bề mặt vật liệu nano silica cấu trúc xốp rỗng cho ứng dụng phân phối thuốc điều trị ung thư.ghiên cứu điều chỉnh cấu trúc và biến tính bề mặt vật liệu nano silica cấu trúc xốp rỗng cho ứng dụng phân phối thuốc điều trị ung thư.
MINISTRY OF EDUCATION AND TRANINING VIETNAM ACADEMY OF SCIENCE AND TECHNOLOGY GRADUATE UNIVERSITY OF SCIENCE AND TECHNOLOGY - Nguyen Thi Ngoc Hoi STRUCTURE-ADJUSTABLE SYNTHESIS OF HOLLOW MESOPOROUS SILICA NANOPARTICLES AND ITS SURFACE MODIFICATION FOR ANTI-CANCER DRUG DELIVERY DOCTORAL THESIS OF MATERIAL SCIENCE Ho Chi Minh City – 2022 MINISTRY OF EDUCATION AND TRANINING VIETNAM ACADEMY OF SCIENCE AND TECHNOLOGY GRADUATE UNIVERSITY OF SCIENCE AND TECHNOLOGY - Nguyen Thi Ngoc Hoi STRUCTURE-ADJUSTABLE SYNTHESIS OF HOLLOW MESOPOROUS SILICA NANOPARTICLES AND ITS SURFACE MODIFICATION FOR ANTICANCER DRUG DELIVERY Speciality: Polymeric and Composite Materials Code: 9440125 DOCTORAL THESIS OF MATERIAL SCIENCE SCIENTIFIC SUPERVISOR: Assoc Prof PhD Nguyen Dai Hai Ho Chi Minh City – 2022 i DECLARATION The work was carried out at the Department of Biomaterials & Bioengineering Institute of Applied Materials Science (IAMS) - Vietnam Academy of Science and Technology (VAST) in Ho Chi Minh City I hereby declare that this is my research work under the scientific guidance of Assoc.Prof.Dr Nguyen Dai Hai The research contents and results presented in this thesis are honest and completely based on my research results The results of this study have not been published on any thesis of the same level Ho Chi Minh, November 18th 2022 NGUYEN THI NGOC HOI ACKNOWLEDGEMENTS First of all, I would like to express my most profound gratitude to my supervisor Assoc Prof., PhD Nguyen Dai Hai – Vice Director of the Institute of Applied Materials Science, and Head of Department of Biomaterials and Bioengineering He has given me the delightful lessons, inspiration, constant motivation and enthusiasm that have surely encouraged and helped me to overpass the difficulties encountered, and exerted great aids for my accomplishment of this thesis research Secondly, my sincere gratitude also goes to the enthusiastic help and favorable supports during my PhD course from Vietnam Academy of Science and Technology (VAST), in general, and especially from Graduate University of Science and Technology (GUST - VAST) and the Institute of Applied Materials Science (IAMS - VAST), in particular Furthermore, it is impossible not to mention the valuable support from MSc Nguyen Dinh Tien Dung and BS Truong Thi Ngoc Hang They contributed great help during the experiments at IAMS Last but not least, I am grateful to have my family and friends, who always encourage and support all over time that makes my thesis experience more meaningful Ho Chi Minh, November 18th 2022 NGUYEN THI NGOC HOI TABLE OF CONTENTS Page DECLARATION i ACKNOWLEDGEMENTS ii TABLE OF CONTENTS iii LIST OF ABBREVIATIONS vii LIST OF FIGURES ix LIST OF DIAGRAMS xiv LIST OF TABLES xv INTRODUCTION CHAPTER LITERATURE REVIEW 1.1 Overview of cancer and cancer treatment 1.1.1 Overview of cancer 1.1.2 Common cancer treatment therapies 1.2 Nanomaterials in cancer treatment 1.2.1 Nanomaterials in anti-cancer drug delivery applications .8 1.2.2 Silica nanomaterials in anti-cancer drug delivery applications 1.3 Research situation of nano silica particles in drug delivery 11 1.3.1 International research situation 11 1.3.2 National research situation 13 1.4 Hollow mesoporous silica nanoparticles (HMSN) 16 1.4.1 Structure of HMSN 16 1.4.2 Synthesis methods of HMSN 16 1.4.3 Reaction mechanisms in the synthesis of HMSN by silica based hardtemplate method 24 1.4.4 Modular factors in HMSN fabrication 29 1.4.5 Modification of HMSN 38 1.4.6 Multiple Drugs Loading HMSN 43 CHAPTER MATERIALS AND EXPERIMENTAL METHODS .46 2.1 Materials 46 2.1.1 Chemicals 46 2.1.2 Equipments 47 2.2 Synthesis Methods 48 2.2.1 Synthesis of HMSN 48 2.2.2 Study the effect of PEG on the mesoporous shell thickness of HMSN .51 2.2.3 Study the effect of non-ionic surfactants on the mesopore diameter of HMSN 53 2.2.4 Surface Modification Method of HMSNs with Pluronics .54 2.2.5 Study the effect of Pluronics on dual-drugs delivery characteristics of HMSN-Plu 57 2.3 Physicochemical Analysis Methods 58 2.4 Drug loading and in vitro release study 59 2.5 Cell culture and MTT assay 60 2.6 Statistical analysis 60 CHAPTER A MODIFIED HARD-TEMPLATE METHOD FOR HOLLOW MESOPOROUS SILICA NANOPARTICLES SYNTHESIS WITH SUITABLE PARTICLE SIZE AND SHORTENED SYNTHETIC TIME……………… 61 3.1 Synthesis of silica hard-template 61 3.2 Etching over time of silica hard-template in the synthesis of HMSN 62 3.3 Characterizations of synthesized HMSN 64 3.4 Cytotoxicity of synthesized HMSN 67 3.5 Summary 67 CHAPTER SIMPLY AND EFFECTIVELY CONTROL THE SHELL THICKNESS OF HOLLOW MESOPOROUS SILICA NANOPARTICLES BY POLYETHYLENE GLYCOL FOR DRUG DELIVERY APPLICATIONS 69 4.1 Effect of PEG molecular weight on the mesoporous shell thickness of dSiO2@MSN .69 4.2 Effect of PEG weight percentage on the mesoporous shell thickness of dSiO2@MSN .71 4.3 Characterizations of the synthesized HMSNs 75 4.3.1 Drug loading and in vitro drug release study of the synthesized HMSN 77 4.4 Cytotoxicity of the synthesized HMSN 79 4.5 Summary 79 CHAPTER NON-IONIC SURFACTANTS AS CO-TEMPLATES TO CONTROL THE MESOPORE DIAMETER OF HOLLOW MESOPOROUS SILICA NANOPARTICLES FOR DRUG DELIVERY APPLICATIONS 82 5.1 Preparation of mixed micelles of non-ionic surfactants with CTAB .82 5.2 Effect of non-ionic surfactants on the mesoporous shell thickness of dSiO2@MSN .84 5.3 Effect of non-ionic surfactants on the mesopore diameter of dSiO2@MSN .86 5.4 Characterizations of the synthesized HMSNs 88 5.5 Drug loading and in vitro drug release study of the synthesized HMSNs 90 5.6 Cytotoxicity of the synthesized HMSNs 91 5.7 Summary 92 CHAPTER SURFACE MODIFICATION OF HOLLOW MESOPOROUS SILICA NANOPARTICLES WITH PLURONICS FOR DUAL DRUGS DELIVERY 94 6.1 Activation Pluronic with NPC 94 6.2 Amination of HMSNs’ surface 95 6.3.Modification of HMSNs’ surface with Pluronics via amine intermediate 97 6.4 Dual drugs loading capacity and in vitro release behavior of HMSNPlu…… 100 6.5 In vitro drug release behavior of HMSN-Plu 101 6.6 Cytotoxicity of HMSN-Plu 104 6.7 Characterizations of the HMSN-F127 105 6.8 Cancer cell killing ability of DOX.QUE@HMSN-Plu 109 6.9 Summary 110 CONCLUSIONS AND FUTURE PROSPECTS 111 Conclusion 111 Novelty of the thesis 112 Future perspective 113 LIST OF PUBLICATIONS 114 REFERENCES 115 APPENDIX 129 LIST OF ABBREVIATIONS APTES BET BJH BTES C18TMS CMC CTAB CTAC DI DLC DLE DLS DOX dSiO2 EDX EPR FDA FESEM FT-IR GPC HMSN HPLC MCM-41 MCM-48 MCM-50 MDR MON MSN PAA PBS PEG PEO PPO PMMA (3-Aminopropyl)triethoxysilane Brunauer-Emmett-Teller Barret Joyner and Halenda Bis (triethoxysilylpropyl) disulfide n-octadecyltrimethoxysilan Critical micelle concentration Cetyltrimethylammonium Bromide Cetyltrimethylammonium Chloride Deioned water Drug loading capacity Drug loading efficiency Dynamic Light Scattering Doxorubicin dense Silicone dioxide Energy Dispersive X-ray Enhanced Permeability and Retention Food and Drug Administration Field Emission Scanning Electron Microscope Fourier Transform Infrared Gel Permeation Chromatography Hollow Mesoporous Silica Nanoparticles High Performance Liquid Chromatography Mobil Composition of Matter No 41 Mobil Composition of Matter No 48 Mobil Composition of Matter No 50 Multidrug Resistance Mesoporous Organosilica Nanoparticle Mesoporous Silica Nanoparticles Poly (Acrylic Acid) Phosphate Buffered Saline Polyethylene Glycol Poly(Ethylene Oxide) Poly(Propylene Oxide) Polymethylmethacrylate PS PVP QUE RB SBA-15 SEM TGA TEA TEM TEOS XRD Polystyrene Polyvinylpyrolidone Quercetin Rose Bengal Santa Barbara Amorphous-15 Scanning electron microscope Thermogravimetric analysis Triethanolamine Transmission electron microscopy Tetraethyl orthosilicate X-ray Diffraction DLS size of HMSN-F68 DLS size of HMSN-F127 Zeta potential of dSiO2 Zeta potential of HMSN Zeta potential of HMSN-NH2 Zeta potential of HMSN-L64 Zeta potential of HMSN-F68 Zeta potential of HMSN-F127 TGA graph of HMSN TGA graph of HMSN-L64 TGA graph of HMSN-F68 TGA graph of HMSN-F127 EDX pattern of HMSN EDX pattern of HNSM-NH2 Isotherm Linear Plot of HMSN BJH Adsorption dV/dD Pore Volume of HMSN Isotherm Linear Plot of HMSN-NH2 BJH Adsorption dV/dD Pore Volume of HMSN-NH2 ... mesoporous silica nanoparticles, core-shell mesoporous silica nanoparticles and yolk-shell mesoporoussilicananoparticles (Figure 1.5) [9] Figure 1.5 Structural classification of Mesoporous Silica Nanoparticles... delivery, including inorganic nano- carriers (gold nanoparticles, mesoporous silica, carbon nanotubes, calcium phosphate) ), polymer nano- carriers (nano gels, solid lipid nanoparticles, micelles, dendrimers)... showed that nanosilica was beneficial in enhancing the growth of chili papper plants [40] In 2017, oligochitosan - nano silica preparations (pH 5, oligochitosan MW 4-6 kDa, silica nanoparticle