人類白蛋白及聚苯乙烯磺酸修飾之金奈米棒作為熱觸發式藥物遞送載體應用於光熱治療合併化療之研究

藥物遞送系統結合多模式合併的治療方式應用在腫瘤診斷與治療相關領域相當具有前景。此篇研究開發出一種新型的藥物遞送載體(GNR/PSS/HSA NPs)，透過雷射穿透式電子顯微鏡、表面電性與傅里葉轉換紅外光譜進行聚苯乙烯磺酸與人類血清白蛋白之表面修飾的鑑定，此外，化療藥物Doxorubicin (DOX)成功透過靜電作用力與疏水作用力搭載上經修飾過之奈米金棒，且此藥物遞送系統(DOX@GNR/PSS/HSA NPs)展現高度的生物相容性與良好的穩定性，而其在近紅外光波段具有強吸收的特性，能夠高效率地將光能轉換成熱能，應用在光熱治療上。另一方面，此載體系統透過兩種藥物觸發釋放模式(蛋白酶作用與近紅外光照射)來傳遞化療藥物，使得在腫瘤處有較多的藥物累積，進而達到顯著的化療效果。更重要的是，從體外試驗與體內試驗的實驗結果都可觀察到，相較於單獨給予化療或光熱治療，以此篇研究開發的藥物遞送載體(DOX@GNR/PSS/HSA NPs)同時進行化療合併光熱治療能夠達到最佳的腫瘤抑制效果。以上的結果表明DOX@GNR/PSS/HSA NPs具有相當大的潛力應用在腫瘤治療。

關鍵字

金奈米棒；人類血清白蛋白；化學治療；光熱治療；控制藥物釋放

並列摘要

Drug delivery systems combined multimodal therapy strategies are very promising in cancer theranostic applications. In this work, a new drug-delivery vehicles based on human serum albumin (HSA)-coated gold nanorods(GNR/PSS/HSA NPs) is developed. The success of coating was verified by transmission electron microscopy (TEM), zeta potential and fourier transform infrared spectroscopy (FTIR). Furthermore, it is demonstrated that doxorubicin (DOX) is successfully loaded among multilayered gold nanorods by the electrostatic and hydrophobic force, and DOX@GNR/PSS/HSA NPs are highly biocompatible and stable in various physiological solutions. The NPs possess strong absorbance in near-infrared (NIR) region, and high photothermal conversion efficiency for outstanding photothermal therapy applications. Moreover, a bimodal drug release triggered by proteinase or NIR irradiation has been revealed, resulting in a significant chemotherapeutic effect in tumor sites because of the preferential drug accumulation and triggered release. Importantly, the in vitro and in vivo experiments demonstrated that DOX@GNR/PSS/HSA NPs, which combined photothermal and chemotherapy for tumor therapy, revealing a remarkably superior synergistic anticancer effect over either monotherapy. All these results suggested a considerable potential of DOX@GNR/PSS/HSA NPs nano-platform for antitumor therapy.

並列關鍵字

gold nanorod (GNR) ； human serum albumin (HSA) ； chemotherapy ； photothermal therapy (PTT) ； control drug release

參考文獻

1. Fang, J., H. Nakamura, and H. Maeda, The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Advanced Drug Delivery Reviews, 2011. 63(3): p. 136-151.

2. Maeda, H., et al., Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. Journal of Controlled Release, 2000. 65(1): p. 271-284.

3. Bae, Y., et al., Multifunctional polymeric micelles with folate-mediated cancer cell targeting and pH-triggered drug releasing properties for active intracellular drug delivery. Molecular BioSystems, 2005. 1(3): p. 242-250.

4. Xu, H., F. Meng, and Z. Zhong, Reversibly crosslinked temperature-responsive nano-sized polymersomes: synthesis and triggered drug release. Journal of Materials Chemistry, 2009. 19(24): p. 4183-4190.

5. Kim, H.J., et al., Ultrasound-Triggered Smart Drug Release from a Poly(dimethylsiloxane)– Mesoporous Silica Composite. Advanced Materials, 2006. 18(23): p. 3083-3088.

國際替代計量

人類白蛋白及聚苯乙烯磺酸修飾之金奈米棒作為熱觸發式藥物遞送載體應用於光熱治療合併化療之研究

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