研究生: |
呂正偉 Lu, Cheng-Wei |
---|---|
論文名稱: |
以具有pH應答性的奈米粒子產生細菌聚集及局部光熱效應於感染治療之評估 Bacteria-Specific Aggregation and Local Photothermal Ablation by pH-Responsive Nanoparticles for the Infection Treatment |
指導教授: |
宋信文
Sung, Hsing-Wen |
口試委員: |
王麗芳
莊峻鍠 許源宏 |
學位類別: |
碩士 Master |
系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
論文出版年: | 2017 |
畢業學年度: | 105 |
語文別: | 中文 |
論文頁數: | 31 |
中文關鍵詞: | 抗菌 、靛氰綠 、光熱 、乙二醇幾丁聚醣 、pH應答 、局部高熱 |
外文關鍵詞: | antibacterial, indocyaninegreen, photothermal, glycolchitosan, pH-response, localhyperthermia |
相關次數: | 點閱:3 下載:0 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
目前臨床上針對皮下膿腫 (subcutaneous abscesses) 等細菌性感染,大多是採取投遞抗生素以及清創等治療方法。然而,大量具有抗藥性的細菌產生以及清創過程對病人帶來的痛苦,使現有治療方式逐漸遇到了瓶頸。鑑此,開發新一代的抗菌系統逐漸成為學術界及臨床上的熱門議題。本研究利用單乳化法開發出一個內部載有靛氰綠 (ICG) 且表面修飾了乙二醇幾丁聚醣 (glycol chitosan) 的奈米材料,透過乙二醇幾丁聚醣的pH應答性讓載體針對細菌產生電荷性吸附並形成聚集,減少對周圍組織的影響,再利用近紅外光 (NIR) 的照射,使ICG產生光熱效應來產生抑菌效果。從物化性分析來看,此載體具有良好穩定性、生物相容性、pH應答性及聚菌能力,能夠在NIR照射5分鐘後就升到50℃的殺菌溫度;胞外實驗部分則是透過革蘭氏陰性菌大腸桿菌 (Escherichia coli) 和革蘭氏陽性菌枯草桿菌 (Bacillus subtilis) 來測試載體對於細菌感染的治療效果,結果證實此載體能在細菌周圍產生局部高熱 (local hyperthermia),和單純的整體加熱方法相比其殺菌效率更為顯著,顯示此系統具有應用於臨床上的高度潛能。
Subcutaneous abscesses are focal bacterial infections that are often accompanied with the acidified microenvironment (pH 6-6.6). Two common applied therapies for the abscess management are incision-drainage and systemic administration of antibiotics. However, incision-drainage is a laborious and painful process for patients. Additionally, systemic antibiotic treatment is often accompanied by the evolution of bacterial antibiotic resistance. Therefore, it is an unmet need to develop a reliable antibacterial system to deal with the infections caused by antibiotic-resistant pathogens. The present study reports a system of glycol chitosan-modified, indocyanine green-loaded PLGA nanoparticles (GIP-NPs). According to the physicochemical analysis, this system demonstrates good results in photothermal effect, biocompatibility, pH-response and shelf life. Upon encountering of the acidic environment, GIP-NPs undergo a surface-charge conversion and induce the bacteria-specific aggregation without absorption to the surrounding normal cells. After near-infrared (NIR) irradiation, GIP-NPs can generate local hyperthermia and cause irreversible damage to bacteria. It also shows higher antibacterial effect compared with simply increasing bulk temperature. These experimental results reveal the strong potential of GIP-NPs for the antibacterial therapy in the next generation.
1. Hsiao, C.-W., et al., Effective Photothermal Killing of Pathogenic Bacteria by Using Spatially Tunable Colloidal Gels with Nano-Localized Heating Sources. Advanced Functional Materials, 2015. 25(5): p. 721-728.
2. Weidenmaier, C., et al., Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections. Nat Med, 2004. 10(3): p. 243-5.
3. Trevani, A.S., et al., Extracellular Acidification Induces Human Neutrophil Activation. The Journal of Immunology, 1999. 162(8): p. 4849.
4. Thet, N.T., et al., Prototype Development of the Intelligent Hydrogel Wound Dressing and Its Efficacy in the Detection of Model Pathogenic Wound Biofilms. ACS Applied Materials & Interfaces, 2015.
5. Ladd, A.P., M.S. Levy, and J. Quilty, Minimally invasive technique in treatment of complex, subcutaneous abscesses in children. J Pediatr Surg, 2010. 45(7): p. 1562-6.
6. Huang, Y.T., et al., Diallyl trisulfide and diallyl disulfide ameliorate cardiac dysfunction by suppressing apoptotic and enhancing survival pathways in experimental diabetic rats. Journal of Applied Physiology (1985), 2013. 114(3): p. 402-10.
7. Pan, W.-Y., et al., Synergistic antibacterial effects of localized heat and oxidative stress caused by hydroxyl radicals mediated by graphene/iron oxide-based nanocomposites. Nanomedicine: Nanotechnology, Biology and Medicine, 2016. 12(2): p. 431-438.
8. Feng, L., L. Wu, and X. Qu, New horizons for diagnostics and therapeutic applications of graphene and graphene oxide. Advanced Material, 2013. 25(2): p. 168-86.
9. Li, F., et al., Preparation and characterization novel polymer-coated magnetic nanoparticles as carriers for doxorubicin. Colloids Surf B Biointerfaces, 2011. 88(1): p. 58-62.
10. Kuo, W.S., et al., Biocompatible bacteria@Au composites for application in the photothermal destruction of cancer cells. Chem Commun (Camb), 2008(37): p. 4430-2.
11. Solway, J. and C.G. Irvin, Airway Smooth Muscle as a Target for Asthma Therapy. New England Journal of Medicine, 2007. 356(13): p. 1367-1369.
12. Thomas, L.A., et al., Carboxylic acid-stabilised iron oxide nanoparticles for use in magnetic hyperthermia. Journal of Materials Chemistry, 2009. 19(36): p. 6529.
13. Saxena, V., M. Sadoqi, and J. Shao, Indocyanine green-loaded biodegradable nanoparticles: preparation, physicochemical characterization and in vitro release. Int J Pharm, 2004. 278(2): p. 293-301.
14. Makadia, H.K. and S.J. Siegel, Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers (Basel), 2011. 3(3): p. 1377-1397.
15. Yan, L., et al., A pH-Responsive Drug-Delivery Platform Based on Glycol Chitosan-Coated Liposomes. Small, 2015. 11(37): p. 4870-4.
16. Nafee, N., et al., Chitosan-coated PLGA nanoparticles for DNA/RNA delivery: effect of the formulation parameters on complexation and transfection of antisense oligonucleotides. Nanomedicine, 2007. 3(3): p. 173-83.
17. Budhian, A., S.J. Siegel, and K.I. Winey, Controlling the in vitro release profiles for a system of haloperidol-loaded PLGA nanoparticles. International Journal of Pharmaceutics, 2008. 346(1-2): p. 151-9.
18. Gavini, E., et al., PLGA microspheres for the ocular delivery of a peptide drug, vancomycin using emulsification/spray-drying as the preparation method: in vitro/in vivo studies. Eur J Pharm Biopharm, 2004. 57(2): p. 207-12.
19. Rosca, I.D., F. Watari, and M. Uo, Microparticle formation and its mechanism in single and double emulsion solvent evaporation. Journal of Control Release, 2004. 99(2): p. 271-80.
20. Gao, F., et al., Double Emulsion Templated Microcapsules with Single Hollow Cavities and Thickness-Controllable Shells. Langmuir, 2009. 25(6): p. 3832-3838.
21. Jian, W.H., et al., Indocyanine Green-Encapsulated Hybrid Polymeric Nanomicelles for Photothermal Cancer Therapy. Langmuir, 2015. 31(22): p. 6202-10.
22. Xu, J., et al., The antibacterial mechanism of carvacrol and thymol against Escherichia coli. Letters in Applied Microbiology, 2008. 47(3): p. 174-9.
23. Korupalli, C., et al., Acidity-triggered charge-convertible nanoparticles that can cause bacterium-specific aggregation in situ to enhance photothermal ablation of focal infection. Biomaterials, 2017. 116: p. 1-9.
24. Zheng, M., et al., Robust ICG theranostic nanoparticles for folate targeted cancer imaging and highly effective photothermal therapy. ACS Applied Mater Interfaces, 2014. 6(9): p. 6709-16.
25. Tahara, K., et al., Establishing chitosan coated PLGA nanosphere platform loaded with wide variety of nucleic acid by complexation with cationic compound for gene delivery. Int J Pharm, 2008. 354(1-2): p. 210-6.
26. Subhash, H.M., et al., Optical detection of indocyanine green encapsulated biocompatible poly (lactic-co-glycolic) acid nanoparticles with photothermal optical coherence tomography. Optics Letters, 2012. 37(5): p. 981-983.
27. Tang, Y., et al., Simultaneous delivery of chemotherapeutic and thermal-optical agents to cancer cells by a polymeric (PLGA) nanocarrier: an in vitro study. Pharmaceutical Research, 2010. 27(10): p. 2242-53.
28. Achilefu, S., et al., A novel indocyanine green nanoparticle probe for non invasive fluorescence imaging in vivo. 2009. 7190: p. 71900L.
29. Alander, J.T., et al., A review of indocyanine green fluorescent imaging in surgery. International Journal of Biomedical Imaging, 2012. 2012: p. 940585.
30. Shemesh, C.S., et al., Indocyanine green loaded liposome nanocarriers for photodynamic therapy using human triple negative breast cancer cells. Photodiagnosis Photodynamic Therapy, 2014. 11(2): p. 193-203.
31. Saxena, V., M. Sadoqi, and J. Shao, Enhanced photo-stability, thermal-stability and aqueous-stability of indocyanine green in polymeric nanoparticulate systems. J Photochem Photobiol B, 2004. 74(1): p. 29-38.
32. Bjarnsholt, T., et al., Applying insights from biofilm biology to drug development - can a new approach be developed? Nat Rev Drug Discov, 2013. 12(10): p. 791-808.
33. Halder, S., et al., Alteration of Zeta potential and membrane permeability in bacteria: a study with cationic agents. Springerplus, 2015. 4: p. 672.
34. Tsao, S.M., C.C. Hsu, and M.C. Yin, Garlic extract and two diallyl sulphides inhibit methicillin-resistant Staphylococcus aureus infection in BALB/cA mice. J Antimicrob Chemother, 2003. 52(6): p. 974-80.
35. Li, X., et al., Control of nanoparticle penetration into biofilms through surface design. Chemical Communication (Camb), 2015. 51(2): p. 282-5.
36. Gupta, A., R.F. Landis, and V.M. Rotello, Nanoparticle-Based Antimicrobials: Surface Functionality is Critical. F1000Res, 2016. 5.