臺灣博碩士論文加值系統

理想的化療藥物載體應具有腫瘤標靶能力、低毒性並能夠有效治療具抗藥性之腫瘤組織。本研究中提出一兼具光觸發藥物釋放、磁場引導以及腫瘤分子影像功能之新式治療診斷奈米藥物載體。此載體主要組成為聚乳酸-甘醇酸共聚物，具有良好的生物相容性及生物可降解性，此高分子材料已通過美國食品藥物管理局(FDA)核准於臨床醫學使用，使用PLGA奈米粒子作為藥物傳遞的載體具有保護藥物活性、降低藥物毒性及改善藥物於水溶液中穩定性等優點。本研究中應用單層乳化法，已成功地將化療藥物阿黴素(doxorubicin，DOX)、超順磁氧化鐵奈米粒子(SPIONs)及具有光熱效應的金奈米棒(Au NRs)同時包覆於PLGA奈米粒子的疏水核心中，得到粒徑約為200 nm；表面電位為- 24 mV的氧化鐵奈米粒子/金奈米棒/阿黴素/聚乳酸-甘醇酸奈米粒子(DOX@SPIONs/ Au NRs/ PLGA nanoparticle, DOX@SAPP)。
經實驗證實，DOX@SAPP具有以下特點:親水性表面---外層覆蓋親水性聚乙二醇高分子(PEG)，有助於維持粒子分散性與延長其於生物體內之循環時間；高裝載效率---藥物包覆量約為3.77 %； SPIONs包覆量約為5.8 %，透過加入O.D值分別為33、100、300金奈米棒濃度可得到1.31 %、2.73 %及8.19 %的裝載效率；良好的穩定性---將載體系統分散於水、PBS、25 % FBS DMEM、100 % FBS等溶液中，三日內皆呈現優良的穩定性，在PBS中更穩定分散長達十五日以上；磁導引及腫瘤分子影像---該載體具超順磁特性，其飽和磁化量為3.04 emu/g，外加磁場下可成功吸引並累積於腫瘤細胞周邊，內吞載體的細胞可產生良好的MRI對比影像。透過細胞測試結果發現，DOX@SAPP可透過細胞內吞途徑(endocytosis)克服抗藥性細胞株不易累積藥物的限制，於外加磁場下可進一步提高細胞內載體累積量。於適當波長之雷射照射下，金奈米棒所產生之光熱效應可超越PLGA的玻璃轉換溫度(49˚C)，促使藥物迅速釋放，結果顯示所開發的DOX@SAPP兼具光熱與化學合併治療效應對於腫瘤細胞有極佳之殺傷力，並成功克服傳統化療藥物於治療抗藥性癌細胞上的限制。

An ideal carrier for chemotherapeutics delivery shall contain features such as cancer cell-targeting capability, low cytotoxicity and efficient killing effect on multiple drug resistant cancer cells. In this study, we proposed a novel nano-sized drug delivery system combining the advantages of: (1) NIR-triggered drug release; (2) magnetically-targeting and (3) magnetic resonance imaging (MRI) contrast. The drug carrier is mainly composed of poly-lactic-co-glycolic acid (PLGA), which is a highly biocompatible, biodegradable and US Food and Drug Administration (FDA)-approved materials for clinical uses. PLGA is widely used for drug delivery applications due to its advantages on protecting drug from loss of activity, reducing drug-associated cytotoxicity and improving drug stability. By utilizing single emulsion method, we have successfully encapsulated doxorubicin (a chemotherapeutic drug), superparamagnetic iron oxide nanoparticles (SPIONs) and gold nanorods (Au NRs) within the hydrophobic core of PLGA nanoparticles (NP). The size and surface potential of the resultant AFP were approximately 200 nm
and -24 mV respectively.
The prepared DOX@SPIONs/Au NRs/ PLGA nanoparticle(DOX@SAPP)were successfully verified with the following features, including: (1) Hydrophilic nanoparticle surface: the DOX@SAPP were covered with hydrophilic polyethylene glycol (PEG), which helps maintaining particle stability and may extend its in vivo circulation time. (2) Capability of loading of various theranostic materials: The loading contents for doxorubicin, SPIONs were 3.77% and 5.8% respectively. By tuning the feeding amount of dodecane-Au NRs (O.D. value 33, 100 and 300), PLGA nanoparticles with different Au NRs loading content (1.31%, 2.73% and 8.19%) can be prepared. (3) Well colloidal stability: the prepared DOX@SAPP were stable up to 3 days in various mediums such as: water, PBS and 25% FBS DMEM medium. The size of DOX@SAPP was not changed significantly in PBS for 15 days. (4) Magnetically-assisted drug delivery and MRI contrast: the DOX@SAPP exhibits superparamagnetism with the saturation magnetization of 3.04 emu/g. The cellular uptake of DOX@SAPP was greatly enhanced by the presence of external magnetic field. Cell-number dependent T2-weighing MRI was demonstrated from the DOX@SAPP -uptake cancer cells. The DOX@SAPP enters cells via endocytosis which can avoid the “drug pumping out” effect by multiple drug resistant cancer cells. Under the irradiation of NIR, the Au NRs-mediated photothermal effect effectively triggered rapid drug release from DOX@SAPP Finally, the combined photothermal- and chemo- therapeutic effect was successfully demonstrated on astrocytoma tumor cell line (ALTS1C1), human breast cancer cells (MCF7) and its multiple drug resistant strain (ADR-MCF7).

摘要……………………………………………………………………………………2
ABSTRACT…………………………………………………………………………3
目錄……………………………………………………………………………………5
圖目錄…………………………………………………………………………………7
表目錄…………………………………………………………………………………9
第一章、 緒論………………………………………………………………10
1.1前言…………………………………………………………………………10
1.2 研究動機與目的……………………………………………………………11
第二章、 文獻回顧
2.1 癌症化學治療與藥物傳遞……………………………………………12
2.2 奈米藥物載體
2.2.1微脂體…………………………………………………………..……15
2.2.2生物可降解高分子奈米藥物載體…………………..………………17
2.2.3 脂質--高分子奈米藥物載體………………………………………23
2.3 複合金屬奈米粒子之智慧型藥物運輸系統
2.3.1氧化鐵奈米粒子………………………………………………….…24
2.3.1金奈米粒子………………………………………………….………27
第三章、實驗材料與方法
3.1金奈米棒的合成……………………………………………………..………30
3.2金奈米棒的表面修飾………………………………………………………30
3.3 氧化鐵奈米粒子(SPIONs)的合成…………………………………………31
3.4 SAPP的製備………………..…………………………………………32
3.5 DOX@SAPP基本性質分析………………………………………………32
3.6 DOX@SAPP近紅外光誘發控制藥物釋放測試………………………32
3.7細胞存活率測試……………………………………………………………33
3.8 細胞磁吸測試………………………………………………………………33
3.9 細胞螢光顯微鏡影像……………………………………………………34
3.10 光熱/化療合併效果……………………………………………………34
第四章、實驗結果與討論
4.1金奈米棒的合成與修飾………………………………………..……………35
4.2 超順磁氧化鐵奈米粒子的合成..……………………..………………38
4.2 SAPP的製備………………………………………………………………39
4.3 DOX@SAPP的穩定性………………………………………………46
4.4 DOX@SAPP的光熱效應…………………………………………………47
4.5 DOX@SAPP的磁滯曲線分析…………………………………………50
4.6 DOX@SAPP之MRI影像………………………………………………51
4.7 細胞存活率測試………………………………………………………52
4.8 細胞吞噬能力(In vitro cellular uptake) ……………………………54
4.9 DOX@SAPP於腫瘤的光熱/化療合併效果……………………………59
第五章、 結論與未來展望……………………………………………………63
第六章、參考文獻……………………………………………………………64

1. Geffen, D.B. and S. Man, New drugs for the treatment of cancer, 1990-2001. Isr Med Assoc J, 2002. 4(12): p. 1124-31.
2. Hsiang, Y.H., et al., Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem, 1985. 260(27): p. 14873-8.
3. Tewey, K.M., et al., Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science, 1984. 226(4673): p. 466-8.
4. Horwitz, S.B., et al., Taxol: mechanisms of action and resistance. J Natl Cancer Inst Monogr, 1993(15): p. 55-61.
5. Longley, D.B., D.P. Harkin, and P.G. Johnston, 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer, 2003. 3(5): p. 330-8.
6. Raguz, S. and E. Yague, Resistance to chemotherapy: new treatments and novel insights into an old problem. British Journal of Cancer, 2008. 99(3): p. 387-391.
7. Wong, H.L., et al., A mechanistic study of enhanced doxorubicin uptake and retention in multidrug resistant breast cancer cells using a polymer-lipid hybrid nanoparticle system. J Pharmacol Exp Ther, 2006. 317(3): p. 1372-81.
8. Wang, A.Z., R. Langer, and O.C. Farokhzad, Nanoparticle Delivery of Cancer Drugs. Annual Review of Medicine, Vol 63, 2012. 63: p. 185-198.
9. Beija, M., et al., Colloidal systems for drug delivery: from design to therapy. Trends in Biotechnology, 2012. 30(9): p. 485-496.
10. Albanese, A., P.S. Tang, and W.C. Chan, The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng, 2012. 14: p. 1-16.
11. Brannon-Peppas, L. and J.O. Blanchette, Nanoparticle and targeted systems for cancer therapy. Advanced Drug Delivery Reviews, 2012. 64: p. 206-212.
12. Longmire, M., P.L. Choyke, and H. Kobayashi, Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine, 2008. 3(5): p. 703-717.
13. Osada, K., R.J. Christie, and K. Kataoka, Polymeric micelles from poly(ethylene glycol)-poly(amino acid) block copolymer for drug and gene delivery. Journal of the Royal Society Interface, 2009. 6: p. S325-S339.
14. Maeda, H., et al., Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release, 2000. 65(1-2): p. 271-84.
15. Brannon-Peppas, L. and J.O. Blanchette, Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev, 2004. 56(11): p. 1649-59.
16. Maeda, H., Tumor-selective delivery of macromolecular drugs via the EPR effect: background and future prospects. Bioconjug Chem, 2010. 21(5): p. 797-802.
17. Byrne, J.D., T. Betancourt, and L. Brannon-Peppas, Active targeting schemes for nanoparticle systems in cancer therapeutics. Advanced Drug Delivery Reviews, 2008. 60(15): p. 1615-1626.
18. Quintana, A., et al., Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor. Pharmaceutical Research, 2002. 19(9): p. 1310-1316.
19. Luqmani, Y.A., Mechanisms of drug resistance in cancer chemotherapy. Med Princ Pract, 2005. 14 Suppl 1: p. 35-48.
20. Mura, S., J. Nicolas, and P. Couvreur, Stimuli-responsive nanocarriers for drug delivery. Nat Mater, 2013. 12(11): p. 991-1003.
21. Bae, Y., et al., Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: Tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. Bioconjugate Chemistry, 2005. 16(1): p. 122-130.
22. Lee, S.M., et al., Polymer-caged lipsomes: A pH-Responsive delivery system with high stability. Journal of the American Chemical Society, 2007. 129(49): p. 15096-+.
23. Wang, C.H., S.T. Kang, and C.K. Yeh, Superparamagnetic iron oxide and drug complex-embedded acoustic droplets for ultrasound targeted theranosis. Biomaterials, 2013. 34(7): p. 1852-1861.
24. Huang, S.L. and R.C. MacDonald, Acoustically active liposomes for drug encapsulation and ultrasound-triggered release. Biochim Biophys Acta, 2004. 1665(1-2): p. 134-41.
25. Yavuz, M.S., et al., Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nature Materials, 2009. 8(12): p. 935-939.
26. Dong, X. and R.J. Mumper, Nanomedicinal strategies to treat multidrug-resistant tumors: current progress. Nanomedicine (Lond), 2010. 5(4): p. 597-615.
27. Dong, X., et al., Doxorubicin and paclitaxel-loaded lipid-based nanoparticles overcome multidrug resistance by inhibiting P-glycoprotein and depleting ATP. Cancer Res, 2009. 69(9): p. 3918-26.
28. Jin, S.E., H.E. Jin, and S.S. Hong, Targeted delivery system of nanobiomaterials in anticancer therapy: from cells to clinics. Biomed Res Int, 2014. 2014: p. 814208.
29. Etheridge, M.L., et al., The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine-Nanotechnology Biology and Medicine, 2013. 9(1): p. 1-14.
30. Al-Jamal, W.T. and K. Kostarelos, Liposomes: from a clinically established drug delivery system to a nanoparticle platform for theranostic nanomedicine. Acc Chem Res, 2011. 44(10): p. 1094-104.
31. Malam, Y., M. Loizidou, and A.M. Seifalian, Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci, 2009. 30(11): p. 592-9.
32. Torchilin, V.P., Recent advances with liposomes as pharmaceutical carriers. Nature Reviews Drug Discovery, 2005. 4(2): p. 145-160.
33. Immordino, M.L., F. Dosio, and L. Cattel, Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine, 2006. 1(3): p. 297-315.
34. Andriyanov, A.V., et al., Therapeutic efficacy of combining pegylated liposomal doxorubicin and radiofrequency (RF) ablation: comparison between slow-drug-releasing, non-thermosensitive and fast-drug-releasing, thermosensitive nano-liposomes. PLoS One, 2014. 9(5): p. e92555.
35. Leung, S.J. and M. Romanowski, Light-activated content release from liposomes. Theranostics, 2012. 2(10): p. 1020-36.
36. Kumari, A., S.K. Yadav, and S.C. Yadav, Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces, 2010. 75(1): p. 1-18.
37. Dinarvand, R., et al., Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents. Int J Nanomedicine, 2011. 6: p. 877-95.
38. Gopferich, A., Mechanisms of polymer degradation and erosion. Biomaterials, 1996. 17(2): p. 103-114.
39. Dinarvand, R., et al., Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents. International Journal of Nanomedicine, 2011. 6: p. 877-895.
40. Elzoghby, A.O., Gelatin-based nanoparticles as drug and gene delivery systems: Reviewing three decades of research. Journal of Controlled Release, 2013. 172(3): p. 1075-1091.
41. Cascone, M.G., et al., Gelatin nanoparticles produced by a simple W/O emulsion as delivery system for methotrexate. Journal of Materials Science-Materials in Medicine, 2002. 13(5): p. 523-526.
42. Choubey, J. and A.K. Bajpai, Investigation on magnetically controlled delivery of doxorubicin from superparamagnetic nanocarriers of gelatin crosslinked with genipin. J Mater Sci Mater Med, 2010. 21(5): p. 1573-86.
43. Li, W.M., D.M. Liu, and S.Y. Chen, Amphiphilically-modified gelatin nanoparticles: Self-assembly behavior, controlled biodegradability, and rapid cellular uptake for intracellular drug delivery. Journal of Materials Chemistry, 2011. 21(33): p. 12381-12388.
44. Lu, Z., et al., Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy. Clin Cancer Res, 2004. 10(22): p. 7677-84.
45. Won, Y.W., et al., Nano Self-Assembly of Recombinant Human Gelatin Conjugated with alpha-Tocopheryl Succinate for Hsp90 Inhibitor, 17-AAG, Delivery. Acs Nano, 2011. 5(5): p. 3839-3848.
46. Bajpai, A.K. and J. Choubey, In vitro release dynamics of an anticancer drug from swellable gelatin nanoparticles. Journal of Applied Polymer Science, 2006. 101(4): p. 2320-2332.
47. Amass, W., A. Amass, and B. Tighe, A review of biodegradable polymers: Uses, current developments in the synthesis and characterization of biodegradable polyesters, blends of biodegradable polymers and recent advances in biodegradation studies. Polymer International, 1998. 47(2): p. 89-144.
48. Danhier, F., et al., PLGA-based nanoparticles: an overview of biomedical applications. J Control Release, 2012. 161(2): p. 505-22.
49. Makadia, H.K. and S.J. Siegel, Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers, 2011. 3(3): p. 1377-1397.
50. Astete, C.E. and C.M. Sabliov, Synthesis and characterization of PLGA nanoparticles. J Biomater Sci Polym Ed, 2006. 17(3): p. 247-89.
51. Cheng, J., et al., Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials, 2007. 28(5): p. 869-76.
52. Luo, R., B. Neu, and S.S. Venkatraman, Surface functionalization of nanoparticles to control cell interactions and drug release. Small, 2012. 8(16): p. 2585-94.
53. Tewes, F., et al., Comparative study of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles prepared by single and double emulsion methods. Eur J Pharm Biopharm, 2007. 66(3): p. 488-92.
54. Takenaga, M., et al., Administration of optimum sustained-insulin release PLGA microcapsules to spontaneous diabetes-prone BB/Wor//Tky rats. Drug Deliv, 2006. 13(2): p. 149-57.
55. Hadinoto, K., A. Sundaresan, and W.S. Cheow, Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review. Eur J Pharm Biopharm, 2013. 85(3 Pt A): p. 427-43.
56. Tan, S., et al., Lipid-enveloped hybrid nanoparticles for drug delivery. Nanoscale, 2013. 5(3): p. 860-72.
57. Yang, Z., et al., Targeted delivery of 10-hydroxycamptothecin to human breast cancers by cyclic RGD-modified lipid-polymer hybrid nanoparticles. Biomed Mater, 2013. 8(2): p. 025012.
58. Shi, J., et al., Differentially charged hollow core/shell lipid-polymer-lipid hybrid nanoparticles for small interfering RNA delivery. Angew Chem Int Ed Engl, 2011. 50(31): p. 7027-31.
59. Zhang, L., et al., Self-assembled lipid--polymer hybrid nanoparticles: a robust drug delivery platform. ACS Nano, 2008. 2(8): p. 1696-702.
60. Gupta, A.K. and M. Gupta, Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials, 2005. 26(18): p. 3995-4021.
61. Mahmoudi, M., et al., Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. Adv Drug Deliv Rev, 2011. 63(1-2): p. 24-46.
62. Cole, A.J., V.C. Yang, and A.E. David, Cancer theranostics: the rise of targeted magnetic nanoparticles. Trends Biotechnol, 2011. 29(7): p. 323-32.
63. Chang, M., et al., Homologous RBC-derived vesicles as ultrasmall carriers of iron oxide for magnetic resonance imaging of stem cells. Nanotechnology, 2010. 21(23).
64. Wadajkar, A.S., et al., Design and Application of Magnetic-based Theranostic Nanoparticle Systems. Recent Pat Biomed Eng, 2013. 6(1): p. 47-57.
65. Shun Shen , S.W., Rui Zheng , Xiaoyan Zhu , Xinguo Jiang , Deliang Fu , and W. Yang, Magnetic nanoparticle clusters for photothermal therapy with
near-infrared irradiation. Biomaterials, 2015.
66. Kong, S.D., et al., Magnetic field activated lipid-polymer hybrid nanoparticles for stimuli-responsive drug release. Acta Biomaterialia, 2013. 9(3): p. 5447-5452.
67. Ling, Y., et al., Dual docetaxel/superparamagnetic iron oxide loaded nanoparticles for both targeting magnetic resonance imaging and cancer therapy. Biomaterials, 2011. 32(29): p. 7139-50.
68. Liu, X.Q., et al., Preparation and characterization of biodegradable magnetic carriers by single emulsion-solvent evaporation. Journal of Magnetism and Magnetic Materials, 2007. 311(1): p. 84-87.
69. Yang, J., et al., Antibody conjugated magnetic PLGA nanoparticles for diagnosis and treatment of breast cancer. Journal of Materials Chemistry, 2007. 17(26): p. 2695-2699.
70. Chiang, W.L., et al., Pulsatile Drug Release from PLGA Hollow Microspheres by Controlling the Permeability of Their Walls with a Magnetic Field. Small, 2012. 8(23): p. 3584-3588.
71. Cheng, L., et al., Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy. Biomaterials, 2012. 33(7): p. 2215-22.
72. Murphy, C.J., et al., Anisotropic metal nanoparticles: Synthesis, assembly, and optical applications. Journal of Physical Chemistry B, 2005. 109(29): p. 13857-13870.
73. Spadavecchia, J., et al., Bioconjugated gold nanorods to enhance the sensitivity of FT-SPR-based biosensors. Colloids and Surfaces B-Biointerfaces, 2012. 100: p. 1-8.
74. Huang, X.H., et al., Plasmonic photothermal therapy (PPTT) using gold nanoparticles. Lasers in Medical Science, 2008. 23(3): p. 217-228.
75. Chen, C.L., et al., In situ real-time investigation of cancer cell photothermolysis mediated by excited gold nanorod surface plasmons. Biomaterials, 2010. 31(14): p. 4104-12.
76. Huff, T.B., et al., Hyperthermic effects of gold nanorods on tumor cells. Nanomedicine (Lond), 2007. 2(1): p. 125-32.
77. Tong, L., et al., Gold nanorods mediate tumor cell death by compromising membrane integrity. Advanced Materials, 2007. 19(20): p. 3136-+.
78. Schnarr, K., et al., Gold Nanoparticle-Loaded Neural Stem Cells for Photothermal Ablation of Cancer. Advanced Healthcare Materials, 2013. 2(7): p. 976-982.
79. Chang, Y.T., et al., Near-Infrared Light-Responsive Intracellular Drug and siRNA Release Using Au Nanoensembles with Oligonucleotide-Capped Silica Shell. Advanced Materials, 2012. 24(25): p. 3309-3314.
80. Huang, Y., et al., Biomedical nanomaterials for imaging-guided cancer therapy. Nanoscale, 2012. 4(20): p. 6135-49.
81. Alkilany, A.M., et al., Gold nanorods: Their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions. Advanced Drug Delivery Reviews, 2012. 64(2): p. 190-199.
82. Zhang, Z.J., et al., Mesoporous Silica-Coated Gold Nanorods as a Light-Mediated Multifunctional Theranostic Platform for Cancer Treatment. Advanced Materials, 2012. 24(11): p. 1418-1423.
83. Sau, T.K. and C.J. Murphy, Seeded high yield synthesis of short Au nanorods in aqueous solution. Langmuir, 2004. 20(15): p. 6414-6420.
84. Kinnear, C., et al., Gold Nanorods: Controlling Their Surface Chemistry and Complete Detoxification by a Two-Step Place Exchange. Angewandte Chemie-International Edition, 2013. 52(7): p. 1934-1938.
85. Thierry, B., et al., A robust procedure for the functionalization of gold nanorods and noble metal nanoparticles. Chem Commun (Camb), 2009(13): p. 1724-6.
86. Sun, H.L., et al., Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin. Biomaterials, 2009. 30(31): p. 6358-6366.
87. Peng, C.A. and S. Pachpinde, Longitudinal Plasmonic Detection of Glucose Using Gold Nanorods. Nanomaterials and Nanotechnology, 2014. 4.
88. Chevalier, Y. and M.A. Bolzinger, Emulsions stabilized with solid nanoparticles: Pickering emulsions. Colloids and Surfaces a-Physicochemical and Engineering Aspects, 2013. 439: p. 23-34.
89. Vilchez, A., et al., Antagonistic Effects between Magnetite Nanoparticles and a Hydrophobic Surfactant in Highly Concentrated Pickering Emulsions. Langmuir, 2014. 30(18): p. 5064-5074.
90. Pons, T., et al., Hydrodynamic dimensions, electrophoretic mobility, and stability of hydrophilic quantum dots. J Phys Chem B, 2006. 110(41): p. 20308-16.
91. Huang, X. and C.S. Brazel, On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. Journal of Controlled Release, 2001. 73(2-3): p. 121-136.
92. Shustik, C., W. Dalton, and P. Gros, P-glycoprotein-mediated multidrug resistance in tumor cells: biochemistry, clinical relevance and modulation. Mol Aspects Med, 1995. 16(1): p. 1-78.
93. Li, B., et al., Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies. International Journal of Nanomedicine, 2012. 7: p. 187-197.
94. Nemati, F., et al., Reversion of multidrug resistance using nanoparticles in vitro: Influence of the nature of the polymer. International Journal of Pharmaceutics, 1996. 138(2): p. 237-246.