| Title | Enhanced tumour penetration and prolonged circulation in blood of polyzwitterion-drug conjugates with cell-membrane affinity |
| Authors | Chen, Siqin Zhong, Yin Fan, Wufa Xiang, Jiajia Wang, Guowei Zhou, Quan Wang, Jinqiang Geng, Yu Sun, Rui Zhang, Zhen Piao, Ying Wang, Jianguo Zhuo, Jianyong Cong, Hailin Jiang, Haiping Ling, Jun Li, Zichen Yang, Dingding Yao, Xin Xu, Xiao Zhou, Zhuxian Tang, Jianbin Shen, Youqing |
| Affiliation | Zhejiang Univ, Coll Chem & Biol Engn, Zhejiang Key Lab Smart BioMat, Hangzhou, Peoples R China Zhejiang Univ, Coll Chem & Biol Engn, Ctr Bionanoengn, Hangzhou, Peoples R China Zhejiang Univ, Coll Chem & Biol Engn, Key Lab Biomass Chem Engn, Minist Educ, Hangzhou, Peoples R China Hangzhou Global Sci & Technol Innovat Ctr, Hangzhou, Peoples R China Peking Univ, Dept Polymer Sci & Engn, Beijing, Peoples R China Zhejiang Univ, Affiliated Hosp 1, Dept Surg, Sch Med, Hangzhou, Peoples R China Qingdao Univ, Coll Mat Sci & Engn, Inst Biomed Mat & Engn, Qingdao, Peoples R China Zhejiang Univ, Affiliated Hosp 1, Dept Med Oncol, Sch Med, Hangzhou, Peoples R China Zhejiang Univ, Dept Polymer Sci & Engn, Hangzhou, Peoples R China Univ Chinese Acad Sci, Sch Chem Sci, Beijing, Peoples R China |
| Keywords | ARGININE-RICH PEPTIDES POLYMERIC NANOPARTICLES IN-VIVO DELIVERY NANOMEDICINE ERYTHROCYTE HYPOXIA NANOCARRIERS ADSORPTION RESISTANCE |
| Issue Date | Apr-2021 |
| Publisher | NATURE BIOMEDICAL ENGINEERING |
| Abstract | Conjugates of small-molecule anticancer drugs with a polyzwitterion that has negligible interaction with proteins and a weak interaction with phospholipids eradicate large tumours and patient-derived tumour xenografts in mice. 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 patient-derived tumour xenografts in mice. The simplicity and potency of the polyzwitterion-drug conjugates should facilitate the design of translational anticancer nanomedicines. |
| URI | http://hdl.handle.net/20.500.11897/612470 |
| ISSN | 2157-846X |
| DOI | 10.1038/s41551-021-00701-4 |
| Indexed | SCI(E) |
| Appears in Collections: | å å¦ä¸ å å å·¥ç¨ å¦é ¢ |
