THAI NGUYEN UNIVERSITY THAI NGUYEN UNIVERSITY UNIVERSITY OF AGRICULTURE AND FORESTRY TRAN THI THUY HA TOPIC TITTLE INVESTIGATE OF ALBUMIN COATED POROUS HOLLOW Fe3O4 NANOPARTICLES FOR DUAL DRUGS DELIVE[.]
THAI NGUYEN UNIVERSITY UNIVERSITY OF AGRICULTURE AND FORESTRY TRAN THI THUY HA TOPIC TITTLE: INVESTIGATE OF ALBUMIN COATED POROUS HOLLOW Fe3O4 NANOPARTICLES FOR DUAL DRUGS DELIVERY BACHELOR THESIS Study Mode: Full-time Major: Environmental Science and Management Faculty: International Training and Development Center Batch: 2010-2015 Thai Nguyen, 15/01/2015 n THAI NGUYEN UNIVERSITY UNIVERSITY OF AGRICULTURE AND FORESTRY TRAN THI THUY HA TOPIC TITTLE: INVESTIGATE OF ALBUMIN COATED POROUS HOLLOW Fe3O4 NANOPARTICLES FOR DUAL DRUGS DELIVERY BACHELOR THESIS Study Mode: Full-time Major: Environmental Science and Management Faculty: International Training and Development Center Batch: 2010-2015 Thai Nguyen, 15/01/2015 n Thai Nguyen University of Agriculture and Forestry Degree Program Bachelor of Environmental Science and Management Student name Tran Thi Thuy Ha Student ID DTN1053110065 Thesis Title Investigate of Albumin-Porous Holow Fe3O4 Nanoparticles for Dual Drug Delivery Supervisor(s) Prof Huang Yu-Fen & Dr Do Thi Ngoc Oanh Abstract: Dual-functional drug carrier has been a modern strategy in cancer treatment Photodynamic therapy (PDT) is a non-invasive treatment modality for selective destruction of cancer malignant cells, which involves light irradiation, and a photosensitizer for free radicals generation; hence archiving photocytotoxicity On the other hand, the use of a chemotherapeutic agent is most effective at killing cells that are rapidly dividing However, most of the photosensitizers and chemotherapeutical agents lack of efficient bio-distribution and cellular uptake; for instance the use of nanoparticles provides an ideal carrier of a photodynamic drug In the present work, a photosensitizer drug protoporphyrin IX (PpIX), and a chemotherapeutic drug Doxorubicin (DOX), are encapsulated onto porous hollow iron nanoparticles (PHNPs) via oil in water emulsion procedure using BSA as a stabilizer, with the aim of a synergistic effect through a combination therapy Carriers were successfully characterized; sizes and charges were monitored via DLS and Zeta Potential respectively The intracellular uptake and localization of ii n polymeric particle was investigated by fluorescence microscope The photodynamic effect was evaluated by MTT cytotoxicity assay Together, the dual drug carrier nanoparticle combined chemo-photodynamic therapy strategy in one delivery system, which is a potential dual-functional carrier for the synergistic combination for the treatment of cancer Keywords Porous holow Fe3O4 nanoparticles, drug delivery, albumin Number of pages Date of submission 15th January, 2015 iii n ACKNOWLEAGEMENT Firstly, I would like to say thanks to the cooperation between Thai Nguyen University of Agriculture and Forestry and National Tsing Hua University for providing me an amazing opportunity to internship in Taiwan It brings me great pleasure to work and submit my thesis report for graduation I would like to express my deeply gratitude to Prof Huang Yu-Fen whose guidance, encouragement, suggestion and very constructive criticism have contributed immensely to the evolution of my ideas during the project Without her guidance, I may not have this report I sincerely thank to Dr Do Thi Ngoc Oanh for her advices, assistance, sharing experiences before and after I went to Taiwan, helping me to understand and complete proposal and report I am also thankful to Andrea del Valle for teaching me the synthesis of nanoparticles and various other techniques and methods used in biomedical field She was very helpful in providing me constructive feedback and suggestions on my project and helping me to successful complete several of my experiments and report Without her help and devotion, I would not be able to reach this stage I am really fortunate to be in Prof Huang’s lab Thanks to all the members in Professor Huang’s laboratory who hearty help me a lot when I work in there iv n I also thank to my family for providing me emotional, unceasing encouragement and physical and financial support At last, I would like to thank all those other persons who helped me in completing this report Because of my lack knowledge, the mistake is inevitable, I am very grateful if I receive the comments and opinions from teachers and others to contribute my report Thank you v n TABLE OF CONTENT LIST OF FIGURES LIST OF ABBREVIATIONS PART I INTRODUCTION 1.1 Research rationale 1.2 Research’s objectives 1.3 Research questions 1.4 Limitations 1.5 Definitions PART II LITERATURE REVIEW 2.1 Cancer Problem 2.2 Photodynamic Therapy 2.3 Nanoparticles in biomedical application 2.4 Protein coated nanoparticles 2.5 Albumin coated nanoparticles 2.6 Bovine Serum Albumin (BSA) 10 2.7 Porous hollow Fe3O4 nanoparticles 10 2.8 Cancer treatment Drugs 12 2.8.1 DOXorubicin 12 vi n 2.8.2 Protoporphyrin IX 13 PART III MATERIALS AND METHODS 15 3.1 Materials 15 3.2 Treatments 17 3.3 Procedure 18 3.4 Experiment 1: Characterization of nanocarrier 18 3.4.1 Particle Size and Surface charge Measurement 18 3.4.2 Encapsulation Efficiency Measurements 19 3.5 Experiment 2: Cytotoxic assay 20 3.5.1 Dark toxicity 20 3.5.2 Light-induced toxicity 20 PART IV RESULTS 22 4.1 Particle size and Surface charge 22 4.2 Efficiency of Drugs Loading 22 4.3 Cytotoxic assay 23 4.3.1 Dark toxicity 23 4.3.2 Light-induced Toxicity i PART V DISCUSSION AND CONCLUSION 24 5.1 Discussion 24 vii n 5.1.1 Particle Size and Surface charge 24 5.1.2 Efficiency Drugs loading 24 5.1.3 Cytotoxic Assay 25 5.1.3.1 Dark Toxicity 25 5.1.3.2 Light-induced Toxicity 26 5.2 Conclusion 26 REFERENCES 28 viii n LIST OF FIGURES Figure 1: Schematic illustration of simultaneous surfactant exchange and cisplatin loading into a PHNP and functionalization of this PHNP with Herceptin 12 Figure 2: Chemical structure of DOX 13 Figure 3: Chemical Structure of PpIX 13 Figure 4: Photodynamic therapy of PpIX 14 Figure 5: Photo of Sonicator 16 Figure 6: Photo of Refrigerated Centrifuge 16 Figure 7: Photo of Plate reader 16 Figure 8: Photograph of four treatments was prepared successfully 17 Figure 9: Schematic diagram of the PHNPs:BSA:DOX:PpIX nanocarrier 21 Figure 10: The average size of PHNPs: BSA: DOX/ PpIX 22 Figure 11: The average zeta potential of PHNPs:BSA:DOX:PpPIX 22 Figure 12: Drug loading efficiency in PHNPs 22 Figure 13: MTT dark cytotoxicity results 23 Figure 14: MTT cytotoxicity results 23 n ... NGUYEN UNIVERSITY UNIVERSITY OF AGRICULTURE AND FORESTRY TRAN THI THUY HA TOPIC TITTLE: INVESTIGATE OF ALBUMIN COATED POROUS HOLLOW Fe3O4 NANOPARTICLES FOR DUAL DRUGS DELIVERY BACHELOR THESIS Study... in one delivery system, which is a potential dual- functional carrier for the synergistic combination for the treatment of cancer Keywords Porous holow Fe3O4 nanoparticles, drug delivery, albumin. .. Investigate of Albumin- Porous Holow Fe3O4 Nanoparticles for Dual Drug Delivery Supervisor(s) Prof Huang Yu-Fen & Dr Do Thi Ngoc Oanh Abstract: Dual- functional drug carrier has been a modern strategy