National Institutes for Food and Drug Control, Institute of Chemical Drug Control, TianTanXiLi 2, Beijing, 100050, China.
Org Biomol Chem. 2019 Jun 5;17(22):5570-5577. doi: 10.1039/c9ob00859d.
Nano drug delivery is a promising domain in biomedical theranostics and has aroused more and more attention in recent years. We report here an amphiphilic polymer TPG1, bearing a H2O2-sensitive benzil and an AIE fluorophore tetraphenylethene (TPE) unit, which is able to self-assemble into spherical nanosized micelles in aqueous solution. Doxorubicin (DOX) can be encapsulated into TPG1 micelles efficiently with the loading capability of up to 59% by weight. The benzil moiety could be cleaved via the Baeyer-Villiger type reaction in the presence of H2O2, leading to the decomposition of TPG1 micelles and release of DOX. In vitro studies indicated that DOX-loaded TPG1 micelles can be internalized by cancer cells, followed by unloading encapsulated DOX under the stimulation of H2O2. The drug release process can be monitored by the AIE fluorescence from the degradation products containing a TPE moiety. MTT assays against HeLa and HepG2 cancer cells demonstrated that DOX-loaded micelles showed good anticancer efficacy. The polymer TPG1 and the corresponding decomposed products showed great biocompatibility. Our data suggest that TPG1 has the potential to be employed for the controlled drug delivery system.
纳米药物递送是生物医学治疗学中一个很有前途的领域,近年来引起了越来越多的关注。我们在这里报道了一种两亲性聚合物 TPG1,它带有一个对 H2O2 敏感的二苯甲酮和一个 AIE 荧光团四苯乙烯(TPE)单元,能够在水溶液中自组装成球形纳米级胶束。阿霉素(DOX)可以通过包封到 TPG1 胶束中,其载药量高达 59%(重量)。在 H2O2 的存在下,二苯甲酮部分可以通过 Baeyer-Villiger 型反应断裂,导致 TPG1 胶束的分解和 DOX 的释放。体外研究表明,负载 DOX 的 TPG1 胶束可以被癌细胞内化,然后在 H2O2 的刺激下释放包封的 DOX。药物释放过程可以通过含有 TPE 部分的降解产物的 AIE 荧光来监测。针对 HeLa 和 HepG2 癌细胞的 MTT 测定表明,负载 DOX 的胶束表现出良好的抗癌疗效。聚合物 TPG1 和相应的分解产物表现出很好的生物相容性。我们的数据表明,TPG1 有可能被用于控制药物传递系统。
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