内体
右旋糖酐
细胞内
药物输送
生物物理学
材料科学
衣壳
纳米颗粒
甲基丙烯酸酯
膜
高分子
聚合物
内化
纳米技术
化学
毒品携带者
病毒
细胞
生物化学
生物
病毒学
复合材料
共聚物
作者
Saowanee Wannasarit,Shiqi Wang,Patrícia Figueiredo,Claudia Trujillo,Francesca Eburnea,Lorena Simón‐Gracia,Alexandra Correia,Yaping Ding,Tambet Teesalu,Dongfei Liu,Ruedeekorn Wiwattanapatapee,Hélder A. Santos,Wei Li
标识
DOI:10.1002/adfm.201905352
摘要
Abstract Achieving cellular internalization and endosomal escape remains a major challenge for many antitumor therapeutics, especially macromolecular drugs. Viral drug carriers are reported for efficient intracellular delivery, but with limited choices of payloads. In this study, a novel polymeric nanoparticle (ADMAP) is developed, resembling the structure and functional features of a virus. ADMAP is synthesized by grafting endosomolytic poly(lauryl methacrylate‐ co ‐methacrylic acid) on acetalated dextran. The endosomolytic polymer mimics the capsid protein for endosomal escape, and acetalated dextran resembles the viral core for accommodating payloads. After polymer synthesis, the subsequent controlled nanoprecipitation on a microfluidic device yields uniform nanoparticles with high encapsulation efficiency. At late endosomal pH (5.0), the ADMAP particles successfully destabilize endosomal membranes and release the drug payloads synergistically, resulting in a greater therapeutic efficacy compared with that of free anticancer drugs. Further conjugation of a tumor‐penetrating peptide enhances the antitumor efficacy toward 3D spheroids and finally leads to spheroid disintegration. The unique structure along with the synergistic endosomal escape and drug release make ADMAP nanoparticles favorable for intracellular delivery of antitumor therapeutics.
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