Enhanced tumour penetration and prolonged circulation in blood of polyzwitterion–drug conjugates with cell-membrane affinity
writer：Siqin Chen, Yin Zhong, Wufa Fan, Jiajia Xiang, Guowei Wang, Quan Zhou, Jinqiang Wang, Yu Geng, 等
keywords：非EPR依賴的主動滲透
source：期刊
specific source：Nature Biomedical Engineering
Issue time：2021年
Effective anticancer nanomedicines need to exhibit prolonged circulation in blood, to extravasate and accumulate in tumours, and to be taken up by tumour cells. These contrasting criteria for persistent circulation and cell-membrane affinity have often led to complex nanoparticle designs with hampered clinical translatability. Here, we show that conjugates of small-molecule anticancer drugs with the polyzwitterion poly (2-(N-oxide-N, N-diethylamino) ethyl methacrylate) have long blood-circulation half-lives and bind reversibly to cell membranes, owing to the negligible interaction of the polyzwitterion with proteins and its weak interaction with phospholipids. Adsorption of the polyzwitterion–drug conjugates to tumour endothelial cells and then to cancer cells favoured their transcytosis-mediated extravasation into tumour interstitium and infiltration into tumours, and led to the eradication of large tumours and PDX tumors.
https://www.nature.com/articles/s41551-021-00701-4