Combined cancer therapy with hyaluronan-decorated fullerene-silica multifunctional nanoparticles to target cancer stem-like cells.
Combined cancer therapy with hyaluronan-decorated fullerene-silica multifunctional nanoparticles to target cancer stem-like cells.
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DOI：
10.1016/j.biomaterials.2016.04.030
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发表时间：
2016-08
期刊：
影响因子：
14
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Wang H;Agarwal P;Zhao S;Yu J;Lu X;He X
癌症干细胞样细胞（CSC）对化疗具有抵抗力并且具有高度致瘤性，这有助于肿瘤的发生和治疗后复发。我们开发了一种表面装饰有透明质酸 (HA) 的新型 C60 富勒烯-二氧化硅纳米粒子系统，以靶向乳腺 CSC 上过表达的 CD44 变体。此外，盐酸阿霉素（DOX）和吲哚菁绿（ICG）可以以超高的包封率（> 90％）和载药量（例如，药物与纳米颗粒投料比为1：1时为48.5％，而常用的药物与纳米颗粒投料比为1：20，载药量小于5％）封装在纳米颗粒中。因此，负载DOX和ICG的纳米颗粒可以用作单一纳米平台，在近红外激光照射下实现化疗、光动力和光热联合治疗，在体外和体内有效破坏乳腺CSC，且没有明显的全身毒性。此外，我们发现，在总药物剂量相同的情况下，载药量较高的纳米颗粒（例如，48.5% vs 4.6%）也具有显着更高的抗肿瘤功效。这些结果证明了多功能混合纳米颗粒系统通过消除 CSC 来增强癌症治疗的巨大潜力。
Cancer stem-like cells (CSCs) are resistant to chemotherapy and highly tumorigenic, which contributes to tumor occurrence and post-treatment relapse. We developed a novel C60 fullerene-silica nanoparticle system surface-decorated with hyaluronan (HA) to target the variant CD44 overexpressed on breast CSCs. Furthermore, doxorubicin hydrochloride (DOX) and indocyanine green (ICG) can be encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (> 90%) and loading content (e.g., 48.5% at a drug-to-nanoparticle feeding ratio of 1:1, compared to the commonly used drug-to-nanoparticle feeding ratio of 1:20 with a drug loading content of less than 5%). As a result, the DOX and ICG-laden nanoparticles can be used as a single nanoplatform to achieve combined chemo, photodynamic, and photothermal therapy under near infrared laser irradiation for effective destruction of the breast CSCs both in vitro and in vivo, with no evident systemic toxicity. Moreover, we found the nanoparticles with a higher drug loading content (e.g., 48.5 versus 4.6%) also have significantly higher antitumor efficacy, given the same total drug dose. These results demonstrate the great potential of the multifunctional hybrid nanoparticle system for augmenting cancer therapy by eliminating the CSCs.