Biodegradable Cyclomatrix Polyphosphazene Nanoparticles: A Novel pH-Responsive Drug Self-Framed Delivery System
Biodegradable Cyclomatrix Polyphosphazene Nanoparticles: A Novel pH-Responsive Drug Self-Framed Delivery System
复制标题
可生物降解的环基质聚磷腈纳米颗粒：一种新型 pH 响应药物自框架递送系统
DOI：
10.1021/acsami.8b06114
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发表时间：
2018-08-08
影响因子：
9.5
通讯作者：
Lu, Qinghua
中科院分区：
文献类型：
--
作者：
Hou, Shenglei;Chen, Shuangshuang;Lu, Qinghua
传统的给药系统存在载药量低、治疗效果相对较弱的问题，因此开发高效的新型给药系统变得更加迫切。本研究以抗癌药物为聚合物框架，不使用任何载体，制备了一种新颖的药物递送策略——药物自框架递送系统（DSFDS）。含有两个以上亲核官能团（二醇/二胺）的药物分子（以阿霉素为例）在环境条件下通过温和的沉淀缩聚与六氯环三磷腈直接反应，形成具有生物相容性的药物自框架递送纳米颗粒。由于药物分子之间的共价键作用，具有超高载药量的DSFD纳米颗粒在给药过程中具有稳定的循环特性。然而，DSFDs在细胞内酸性环境下的持续释放使其具有长期的抗癌治疗效果。该策略适用于各种亲疏水药物，为设计高载药和释放可控的给药系统提供了新的平台。
Traditional drug delivery systems suffer from low drug-loading and relatively weak therapeutic efficacy, therefore, development of new drug delivery systems with high-efficiency has become more urgent. In this report, a novel-innovative drug delivery strategy, namely drug self-framed delivery system (DSFDS), is prepared via using anticancer drugs as polymer frame without using any carriers. The drug molecules (exemplified by doxorubicin) containing more than two nucleophilic functional groups (diols/diamines) directly reacted with hexachlorocyclotriphosphazene via mild precipitation polycondensation under ambient conditions, forming biocompatible drug self-framed delivery nanoparticles. Because of the covalent bonding of the drug molecules, DSFD nanoparticles (DSFDs) with super high drug-loading were stable in the circulation during delivery. However, sustained release of drug in the acidic environment within cells endowed DSFDs with long-term anticancer therapeutic efficacy. This strategy is applicable for diverse hydrophilic and hydrophobic drugs and may be a new platform for designing high drug -loading and release-controllable drug delivery systems.