Title Page
Purpose of this Research
Contents
Nomenclature (List of Abbreviations) 14
Abstract and Purpose of Research 16
Study Ⅰ. Chemotherapy-Photothermal therapy in Cancer 22
Background 22
The global disease "Cancer" 22
Current treatment options and its limitations 23
Development of alternate treatment modality 26
Development of light therapy 30
GNRs emerging smart photosensitizer for combination therapy 31
Chapter 1. Combinational Chemotherapy and Photothermal Therapy Using a Gold Nanorod Platform for Cancer Treatment 34
Introduction 35
Enhancing the Biocompatibility and Stability of GNRs 39
Drug Loading 47
Stimuli-Responsive Drug Release 52
Conclusion 67
References 70
Chapter 2. Targeted combination therapy using Paclitaxel encapsulated gold nanorod scaffolds. 77
Abstract 77
Introduction 78
Materials and analytical methods 81
Results and discussion 88
Conclusions 98
References 103
Chapter 3. Simultaneous Cancer Treatment with Photothermal Therapy and Chemotherapy using Gold nanorods coated with Methotrexate conjugated Hyaluronic acid 107
Abstract 108
Introduction 109
Materials and analytical methods 113
Results and discussion 118
Conclusion and Future work 128
Supporting information(S) 129
Reference 133
Study Ⅱ. Background Drug delivery in Chronic Wound To Eradicate Multi-drug resistance (MDR) 144
Background 145
Current Challenges in chronic wound healing is multidrug resistance (MDR) 145
Chapter 4. Light responsive multidrug release using GNRs contained LBL films 159
Abstract 159
Introduction 161
Material and methods 164
Evaluation of thermal elevation efficiency of PPGSGNRs 166
Biocompatibility assessment using live and dead staining. 167
Antimicrobial susceptibility study of release of GS from films 167
Discussion and results 168
Conclusion 179
Reference 180
Chapter 1 63
Table 1. Table for Drug modification, payload increase, biocompatibility 63
Table 2. Table for stimuli responsive drug release 64
Table 3. Table for stimuli responsive drug release 66
Chapter 1 37
Figure 1. Schematic representation of synergistic effect using CHT and PTT using GNRs. 37
Figure 2. Schematic representation of LBL modification for biocompatibility. 40
Figure 3. Schematic representation of direct modification for biocompatibility 43
Figure 4. Schematic representation of nanocomposite modification for biocompatibility. 46
Figure 5. Schematic representation of various GNR modification methods for enhanced drug loading. Reproduced with permission. 48
Figure 6. Schematic illustration of intercalated DOX release from dsDNA by responding to the pH stimuli. Reproduced with permission. 53
Figure 7. Schematic illustration of a synthesis process of the multifunctional microcapsules. Reproduced with permission. 57
Figure 8. Schematic representation of GNR modification for stimuli-responsive drug release. 58
Figure 9. Schematic illustration of the preparation of chitosan using pH-responsive drug release. Reproduced with permission. 59
Figure 10. Schematic representation of GNR modification for targeted drug delivery. 62
Figure 11. Representative NIRF images in vivo. a) NIRF images of A549 tumor-bearing mice injected with cRGD-unmodified and cRGD-modified GNR systems 2, 4, 6, and 8 h after... 62
Chapter 2 90
Figure 1. (a) UV-vis spectra of CTAB-GNRs, TMA-GNRs (TGNRs), PPNRGNRs, PPFANRGNR (b) PPPTXGNR, PPFAPTXGNR (S1) (c) TEM images (d) Zeta potential of... 90
Figure 2. Analysis of temperature elevation (a), (b) depending on laser power (0.8, 1.1, 1.6W/cm⁻²) (c), (d) depending on concentration (0.15, 0.5, 1, 2.5 nM) with laser power 1.6W/cm⁻²... 92
Figure 3. Fluorescence analysis of temperature response release of Nile Red from PP-GNRS scaffold (a) Depending on laser power (0.8,1.1,1.6W/cm⁻²) (b) Released Nile red vs. laser power... 93
Figure 4. Uptake difference for receptor specific analysis before (-) and after (+) addition of free Folic acid (FA) for PPNRGNRs, PPFANRGNRs, Fluorescence analysis using image J. 94
Figure 5. Uptake difference depending on laser irradiation at 1.6W for 1, 5, 10min (FA) for (a) PPNRGNRs, (b) PPFANRGNRs, Fluorescence analysis using image J. 95
Figure 6A. Invitro studies a) Biocompatibility of PPGNRs, PPFAGNRs, b) only PTT c)CHT with PPPTXGNRs, PPFAPTXGNRs d) targeted CHT-PTTusing PPPTXGNRs, PPFAPTXGNRs... 96
Figure 6B. Invitro studies a) targeted CHT-PTTusing PPPTXGNRs, PPFAPTXGNRs at 0.6W 1.6W 5, m 97
Chapter 3 118
Figure 1. (a) UV-vis spectra of CTAB-GNRs, TMA-GNRs (TGNRs), HA@TGNRs, HA- Rho.B@TGNR (b) Zeta potential of CTAB-GNRs, TMA-GNRs (TGNRs), HA@TGNRs, HA-... 118
Figure 2. Analysis of temperature elevation (a) depending on concentration (0.15, 0.5, 1, 2.5 nM) with laser power 1.6W/cm⁻² for 15min (b) depending on laser power (0.8, 1.1, 1.6W/cm⁻²) 119
Figure 3.a) Accumulative concentration of released free RHO.B from HA-RHO.B@TGNRs at variable time with laser irradiation at 1.6W) in PBS 122
Figure 3.b) Accumulative concentration of released free RHO.B from HA-RHO.B@TGNRs at variable temperatures (298, 310, 323, and 343 K) and b) Activation energy of hydrolysis rates of... 123
Figure 4.a) Uptake difference for receptor specific analysis before (-) and after (+) addition of free HA for HA-Rho.B. 124
Figure 4.b) Uptake difference depending on laser irradiation at 1.6W for 1, 5, 10min for in absence and presence of GNRs for HA-Rho.B. 125
Figure 5. Invitro studies a) and b) without NIR using TG, HTG, MHTG for receptor specific cell toxicity. c) Biocompatibility of TG, HTG, MHTG in NIH3T3 without NIR and d) CHT-PTT... 126
Chapter 4 170
Figure 1. Thickness and Contact angle before and after LBL assembly a) zero layer b) 1bilayer c) 5bilayer d) 10 bilayer-(No drug layer) 170
Figure 2. Drug loading a) Drug 1 (IBU) in PSS/LPEI b) Drug 2 GSGNRs in PAA/LPEI with increasing thickness upon increasing bilayers 171
Figure 3. Characterization of using AFM-surface roughness analyses for increasing thickness of drug (1 and 2) layer depending on Number of bilayer 171
Figure 3A. Burst release of IBU from PSS/LPEI 172
Figure 3B. Controlled releases of GS from PPGNRs a) depending on laser power (0.6, 1.6W/cm⁻²) b) depending on time 173
Figure 4a) illustration of migration of NIH3T3 cells after scratch and incubating with LBL using live and dead staining 175
Figure 4b) illustration of biocompatibility of prepare LBL using live and dead staining 176
Figure 5. illustration of temperature increases of Film upon NIR a) temperature increase PBS vs GNRs solution b) laser power depended temperature increase 0.2〈0.6〈1.6W/cm⁻²2 c) Thermal... 175
Figure 6. a) Zone of inhibition in S. aureus and E.coli depending on NIR + and NIR- using GNRs scaffold, only PBS, FreeGNRs, Free GS, c),d),e),f) PPGSGNRs and NIR+ b) image 177
Chapter 2 78
Scheme 1. a) Schematic illustration of encapsulation of hydrophobic drug b) Structure of prepared copolymer (P-PEG): model drug encapsulation and physical adsorption onto GNRs. c)... 78
Scheme 2. illustration of temperature increase upon NIR 81
Scheme 3. illustration of solubility of Nile Red nanoformulation onto GNRs[내용없음] 7
Chapter 3 107
Scheme 1. Schematic illustration of our nanoplatform a) The light responsive combinational therapy using GNRs scaffold for photo thermal therapy and chemotherapy b) The formation of... 107
Chapter 2 100
(S1) Synthesis of PPEG-Folic acid (FA), P-PEG-FA 100
(S1) H1NMR 101
(S2) Uv-vi and Zeta potential Paclitaxel encapsulation in PPFAGNRs and PP GNRs 101
(S3) Free PTX in (Hela) and biocompatibility of PPFAGNRs and PPGNRs (PTX-) in NIH3T3 102
(S4) Live/Dead staining in NIR +/- in Hela cells[내용없음] 7