跨细胞
纳米医学
细胞内
内吞作用
内体
药物输送
内化
内吞循环
高尔基体
细胞生物学
渗透(战争)
纳米技术
生物物理学
生物
材料科学
生物化学
纳米颗粒
细胞
内质网
运筹学
工程类
作者
Guanming Yuan,Ming Hui Li,Yifan Zhang,Qing Dong,Shiqun Shao,Zhuxian Zhou,Jianbin Tang,Jiajia Xiang,Youqing Shen
标识
DOI:10.1002/adma.202400425
摘要
Active transcytosis-mediated nanomedicine transport presents considerable potential in overcoming diverse delivery barriers, thereby facilitating tumor accumulation and penetration. Nevertheless, the persistent challenge lies in achieving a nuanced equilibrium between intracellular interception for drug release and transcytosis for tumor penetration. In this study, a comprehensive exploration is conducted involving a series of polyglutamine-paclitaxel conjugates featuring distinct hydrophilic/hydrophobic ratios (HHR) and tertiary amine-oxide proportions (TP) (OPGA-PTX). The screening process, meticulously focused on delineating their subcellular distribution, transcytosis capability, and tumor penetration, unveils a particularly promising candidate denoted as OPPX, characterized by an HHR of 10:1 and a TP of 100%. OPPX, distinguished by its rapid cellular internalization through multiple endocytic pathways, selectively engages in trafficking to the Golgi apparatus for transcytosis to facilitate accumulation within and penetration throughout tumor tissues and simultaneously sorted to lysosomes for cathepsin B-activated drug release. This study not only identifies OPPX as an exemplary nanomedicine but also underscores the feasibility of modulating subcellular distribution to optimize the active transport capabilities and intracellular release mechanisms of nanomedicines, providing an alternative approach to designing efficient anticancer nanomedicines.
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