Chemistry of Materials
Chemistry of Materials
5 years ago

Bioresponsive Chimaeric Nanopolymersomes Enable Targeted and Efficacious Protein Therapy for Human Lung Cancers in Vivo

Bioresponsive Chimaeric Nanopolymersomes Enable Targeted and Efficacious Protein Therapy for Human Lung Cancers in Vivo
Yan Zou, Jian Zhang, Zhiyuan Zhong, Fenghua Meng, Yifeng Xia, Weijing Yang
Rapidly evolving protein technology has generated hundreds of therapeutic proteins that are promising for treating various human diseases. The clinical use of protein drugs remains, however, limited due to the absence of viable vehicles. Here, we report that anisamide-functionalized bioresponsive chimaeric nanopolymersomes (Anis-BCPs) can efficiently load granzyme B (GrB), a potent apoptotic protein, and enable targeted and efficacious protein therapy for H460 human lung cancer in vivo. Anis-BCPs are readily obtained from poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide-g-lipoic acid)-b-poly(acrylic acid) triblock copolymer. Notably, GrB-loaded Anis-BCPs a display superior antitumor effect toward sigma receptor-overexpressing H460 lung cancer cells (IC50 = 7.8 nM). The in vivo studies reveal that Anis-BCPs have a long circulation time and remarkable tumor accumulation. Interestingly, GrB-loaded Anis-BCPs at 6.24 nmol GrB equiv/kg dose, given either in four injections or one single injection, effectively inhibit H460 tumor growth and significantly improve the survival rate for mice. These robust, bioresponsive, and nontoxic chimaeric nanopolymersomes provide a potential platform for cancer protein therapy as well as basic research on intracellular functional proteins.

Publisher URL: http://dx.doi.org/10.1021/acs.chemmater.7b02953

DOI: 10.1021/acs.chemmater.7b02953

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