Enhanced tumour penetration and prolonged circulation in blood of polyzwitterion-drug conjugates with cell-membrane affinity

被引:249
作者
Chen, Siqin [1 ,2 ,3 ,4 ]
Zhong, Yin [1 ,2 ,3 ]
Fan, Wufa [1 ,2 ,3 ,4 ,5 ]
Xiang, Jiajia [1 ,2 ,3 ,4 ]
Wang, Guowei [1 ,2 ,3 ]
Zhou, Quan [1 ,2 ,3 ,4 ]
Wang, Jinqiang [1 ,2 ,3 ]
Geng, Yu [1 ,2 ,3 ,4 ]
Sun, Rui [1 ,2 ,3 ,4 ]
Zhang, Zhen [1 ,2 ,3 ]
Piao, Ying [1 ,2 ,3 ,4 ]
Wang, Jianguo [6 ]
Zhuo, Jianyong [6 ]
Cong, Hailin [7 ]
Jiang, Haiping [8 ]
Ling, Jun [9 ]
Li, Zichen [5 ]
Yang, Dingding [10 ]
Yao, Xin [10 ]
Xu, Xiao [6 ]
Zhou, Zhuxian [1 ,2 ,3 ,4 ]
Tang, Jianbin [1 ,2 ,3 ]
Shen, Youqing [1 ,2 ,3 ,4 ]
机构
[1] Zhejiang Univ, Coll Chem & Biol Engn, Zhejiang Key Lab Smart BioMat, Hangzhou, Peoples R China
[2] Zhejiang Univ, Coll Chem & Biol Engn, Ctr Bionanoengn, Hangzhou, Peoples R China
[3] Zhejiang Univ, Coll Chem & Biol Engn, Key Lab Biomass Chem Engn, Minist Educ, Hangzhou, Peoples R China
[4] Hangzhou Global Sci & Technol Innovat Ctr, Hangzhou, Peoples R China
[5] Peking Univ, Dept Polymer Sci & Engn, Beijing, Peoples R China
[6] Zhejiang Univ, Affiliated Hosp 1, Dept Surg, Sch Med, Hangzhou, Peoples R China
[7] Qingdao Univ, Coll Mat Sci & Engn, Inst Biomed Mat & Engn, Qingdao, Peoples R China
[8] Zhejiang Univ, Affiliated Hosp 1, Dept Med Oncol, Sch Med, Hangzhou, Peoples R China
[9] Zhejiang Univ, Dept Polymer Sci & Engn, Hangzhou, Peoples R China
[10] Univ Chinese Acad Sci, Sch Chem Sci, Beijing, Peoples R China
关键词
ARGININE-RICH PEPTIDES; POLYMERIC NANOPARTICLES; IN-VIVO; DELIVERY; NANOMEDICINE; ERYTHROCYTE; HYPOXIA; NANOCARRIERS; ADSORPTION; RESISTANCE;
D O I
10.1038/s41551-021-00701-4
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:1019 / +
页数:23
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