Fang Kun, Song Lina, Gu Zhuxiao, Yang Fang, Zhang Yu, Gu Ning
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210009, China.
Department of Chemical Engineering, University of Florida, Florida 32611, United States.
Colloids Surf B Biointerfaces. 2015 Dec 1;136:712-20. doi: 10.1016/j.colsurfb.2015.10.014. Epub 2015 Oct 23.
Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3 wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30 min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.
为了获得更好的特异性靶向性和治疗效果，人们对可控药物递送系统进行了广泛研究以用于癌症治疗。在此，我们制备了负载阿霉素的磁性聚乳酸-羟基乙酸共聚物微球（DOX-MMS），其中阿霉素被包裹在微球核心，高含量（28.3 wt%）的γ-Fe2O3纳米颗粒（氧化铁，IOs）通过静电作用组装在微球表面，以确保对外部交变磁场（ACMF）具有高响应灵敏度。当DOX-MMs被ACMF激活时，PLGA壳层中的IOs既能诱导热效应，又能引发壳层通透性增强从而释放药物。结果表明，暴露于ACMF 30分钟的DOX-MMs的累积药物释放率（21.6%）显著高于未暴露于ACMF的情况（2.8%）（约高7倍）。DOX-MMS产生的热疗与增强的阿霉素释放相结合，有利于体外4T1乳腺癌细胞凋亡以及有效抑制4T1肿瘤异种移植模型中的肿瘤生长。因此，DOX-MMS可优化为一种强大的递送系统，用于高效的磁响应药物释放和化疗热疗。
