An intelligent cell-selective polymersome-DM1 nanotoxin toward triple negative breast cancer.
An intelligent cell-selective polymersome-DM1 nanotoxin toward triple negative breast cancer.
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一种针对三阴性乳腺癌的智能细胞选择性聚合物囊泡-DM1 纳米毒素。
DOI：
10.1016/j.jconrel.2021.11.014
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发表时间：
2021-11
影响因子：
10.8
通讯作者：
Zhong Zhiyuan
中科院分区：
文献类型：
--
作者：
Zhang Yifan;Yue Shujing;Haag Rainer;Sun Huanli;Zhong Zhiyuan
抗体-药物结合物(ADC)是临床肿瘤治疗中最重要的进展之一，但存在药物/抗体比(DAR)低、需要大量抗体、化学成分复杂等根本问题。靶向纳米药物虽然提供了一种很有前途的ADC替代品，但受到药物泄漏和较差的癌症特异性的困扰。在此，我们开发了一种基于抗CD44抗体-多聚体-DM1结合物的智能细胞选择性纳米毒素(aCD44-AP-DM1)，用于有效治疗实体瘤。在自组装过程中，DM1同时偶联到囊泡膜二硫键上，抗CD44抗体被容易地点击到聚合物表面，从而量身定制了一种最佳的aCD44-AP-DM1，其抗体密度可控为5.0，非常DAR为275，药物零泄漏和快速还原响应DM1的释放。ACD44-AP-DM1对MDA-MB-231三阴性乳腺癌、SMMC-7721肝细胞癌和A549非小细胞肺癌细胞的半数抑制浓度(IC50)分别为21.4、3.7和64.6 ng/mL，是非靶向P-DM1的3.6~47.2倍。有趣的是，全身注射CD44-AP-DM1显著抑制了裸鼠皮下移植的MDA-MB-231肿瘤，而瘤内注射在五分之四的小鼠中实现了肿瘤的完全消除，而没有引起毒性。这种智能的细胞选择性纳米毒素已经成为比ADC更好的靶向癌症治疗平台。
Antibody-drug conjugates (ADCs) are among the most significant advances in clinical cancer treatments, however, they are haunted with fundamental issues like low drug/antibody ratio (DAR), need of large amount of antibody, and complex chemistry. Targeted nanomedicines while offering a promising alternative to ADCs are afflicted with drug leakage and inferior cancer-specificity. Herein, we developed an intelligent cell-selective nanotoxin based on anti-CD44 antibody-polymersome-DM1 conjugates (aCD44-AP-DM1) for potent treatment of solid tumors. DM1 was simultaneously coupled to vesicular membraneviadisulfide bonds during self-assembly and anti-CD44 antibody was facilely clicked onto polymersome surface, tailor-making an optimal aCD44-AP-DM1 with a controlled antibody density of 5.0, extraordinary DAR of 275, zero drug leakage and rapid reduction-responsive DM1 release. aCD44-AP-DM1 displayed a high specificity and exceptional cytotoxicity toward MDA-MB-231 triple negative breast cancer, SMMC-7721 hepatocellular carcinoma and A549 non-small cell lung cancer cells with half-maximal inhibitory concentrations (IC50) of 21.4, 3.7 and 64.6 ng/mL, respectively, 3.6–47.2-fold exceeding non-targeted P-DM1. Intriguingly, the systemic administration of aCD44-AP-DM1 significantly suppressed subcutaneous MDA-MB-231 tumor xenografts in nude mice while intratumoral injection achieved complete tumor eradication in four out of five mice, without causing toxicity. This intelligent cell-selective nanotoxin has emerged as a better platform over ADCs for targeted cancer therapy.
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三亚甲基碳酸酯和二硫杂环戊烷三亚甲基碳酸酯的有机催化开环共聚：有机催化剂对共聚动力学和共聚物微观结构的影响
影响因子：
6.2
作者：
Wei Jingjing;Meng Hao;Guo Beibei;Zhong Zhiyuan;Meng Fenghua
通讯作者：
Meng Fenghua
影响因子：
4.9
作者：
Nadkarni, Durgesh, V;Lee, Jamie;Meyer, Debra M.
通讯作者：
Meyer, Debra M.
影响因子：
28.2
作者：
Liu X;Taftaf R;Kawaguchi M;Chang YF;Chen W;Entenberg D;Zhang Y;Gerratana L;Huang S;Patel DB;Tsui E;Adorno-Cruz V;Chirieleison SM;Cao Y;Harney AS;Patel S;Patsialou A;Shen Y;Avril S;Gilmore HL;Lathia JD;Abbott DW;Cristofanilli M;Condeelis JS;Liu H
通讯作者：
Liu H
影响因子：
16.6
作者：
Zhang, Wenjia;Hu, Xianglong;Xing, Da
通讯作者：
Xing, Da
酶触发树状聚合物-药物缀合物的转胞吞作用深入渗透胰腺肿瘤
影响因子：
17.1
作者：
Wang, Guowei;Zhou, Zhuxian;Huang, Pintong
通讯作者：
Huang, Pintong