阿霉素包封的 pH/温敏性和阳离子壳交联磁性药物传递系统的设计。

Design of doxorubicin encapsulated pH-/thermo-responsive and cationic shell-crosslinked magnetic drug delivery system.

机构信息

Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li District, Taoyuan City 32003, Taiwan.

出版信息

Colloids Surf B Biointerfaces. 2022 Jan;209(Pt 2):112168. doi: 10.1016/j.colsurfb.2021.112168. Epub 2021 Oct 21.

DOI:10.1016/j.colsurfb.2021.112168

PMID:34715504

Abstract

The upsurge in cancer cases, such as liver cancer, has claimed millions of lives globally and has prompted the development of novel nanodrug delivery systems. These systems allow cancer drugs to be encapsulated in nanocarriers and delivered to tumor sites, and accordingly, help reduce side effects of the current chemotherapeutic treatments. Herein, we prepared nanocarriers comprising magnetic iron oxide (MIO) nanoparticles that were surface modified with crosslinked Pluronic F127 (PF127) and branched polyethylenimine (bPEI) to form MIOpoly nanocarriers. These nanocarriers were then loaded with doxorubicin (DOX) anticancer drug to form the MIOpoly-DOX complex. The nanocarriers were magnetite and possessed superparamagnetic properties. Small-angle neutron scattering (SANS) analysis indicated that the nanocarriers were thermoresponsive and spherically structured. The characteristic peaks at 1285, 1619, 2844, 2919, 2900, 2840, and 3426 cm, corresponding to those of CN, -NH, -CH, and OH-, confirmed the successful crosslinking, coating of PF127-bPEI polymers on the surface of MIO nanoparticles and DOX conjugation. The bioavailability of the nanocarriers indicated a more than 85% cell viability when using HepG2 liver cancer cells. A pH (54.8% release in 48 h; pH = 5.4) and temperature (51.0% release in 48 h; 42 °C)-dependent release of DOX was observed, displaying a Korsmeyer-Peppas kinetics model at low pH and Weibull model at high temperatures. The high DOX fluorescence observed for MIOpoly-DOX indicated a high cellular uptake enhanced by alternating magnetic field. These results suggest that MIOpoly synthesized using a combined approach of surface crosslinking and grafted with PF127-bPEI appear to offer promising properties as drug delivery system. Therefore, the nanocarriers developed in the study possess a great potential for targeted delivery and thereby circumventing the limitations of conventional chemotherapy.

摘要

癌症病例的增加，如肝癌，在全球范围内已经夺去了数百万人的生命，并促使新型纳米药物传递系统的发展。这些系统允许将癌症药物封装在纳米载体中并递送到肿瘤部位，从而有助于减少当前化疗治疗的副作用。在此，我们制备了包含磁性氧化铁（MIO）纳米粒子的纳米载体，这些纳米粒子的表面用交联的 Pluronic F127（PF127）和支化聚乙烯亚胺（bPEI）进行了修饰，形成了 MIOpoly 纳米载体。然后，将这些纳米载体负载多柔比星（DOX）抗癌药物，形成 MIOpoly-DOX 复合物。纳米载体为磁铁矿，具有超顺磁性。小角中子散射（SANS）分析表明，纳米载体具有热响应性和球形结构。在 1285、1619、2844、2919、2900、2840 和 3426 cm 处的特征峰，对应于 CN、-NH、-CH 和 OH-，证实了成功的交联，PF127-bPEI 聚合物在 MIO 纳米粒子表面的涂层和 DOX 缀合。纳米载体的生物利用度表明，使用 HepG2 肝癌细胞时，细胞活力超过 85%。观察到 pH（48 h 时释放 54.8%；pH=5.4）和温度（48 h 时释放 51.0%；42°C）依赖性的 DOX 释放，在低 pH 下表现出 Korsmeyer-Peppas 动力学模型，在高温下表现出 Weibull 模型。对于 MIOpoly-DOX 观察到的高 DOX 荧光表明，交变磁场增强了细胞摄取。这些结果表明，使用表面交联和接枝 PF127-bPEI 的组合方法合成的 MIOpoly 似乎具有作为药物传递系统的有前途的特性。因此，研究中开发的纳米载体具有作为靶向递送的巨大潜力，从而避免了传统化疗的局限性。