ACS Nano: Minimalist Nanovaccine with Optimized Amphiphilic Copolymers for Cancer Immunotherapy

Title：

Minimalist Nanovaccine with Optimized Amphiphilic Copolymers for Cancer Immunotherapy

Authors：

Le Niu^1#, Zhiqin Cao^1#, Yu Miao¹, Ting Wei¹, Jiafei Zhu¹, Maoyi Li¹, Boxiong Bai¹, Linfu Chen¹, Nanhui Liu¹, Feng Pan², Jun jie Zhu², Cheng Wang¹, Yang yang^2,3 and Qian Chen¹*

Institutions：

¹Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China

²Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China

³School of Materials Science and Engineering, Tongji University, Shanghai, 201804, China

Abstract：

Cancer vaccines with the ability to elicit tumor-specific immune responses have attracted significant interest in cancer immunotherapy. A key challenge for effective cancer vaccines is the spatiotemporal codelivery of antigens and adjuvants. Herein, we synthesized a copolymer library containing nine poly(ethylene glycol) methyl ether methacrylate-co-butyl methacrylate-co-2-(azepan-1-yl)ethyl methacrylate (PEGMA-co-BMA-co-C7AMA) graft copolymers with designed proportions of different components to regulate their properties. Among these polymers, C-25, with a C7AMA:BMA ratio at 1.5:1 and PEG wt % of 25%, was screened as the most effective nanovaccine carrier with enhanced ability to induce mouse bone marrow-derived dendritic cell (BMDC) maturation. Additionally, RNA-sequencing (RNA-Seq) analysis revealed that C-25 could activate dendritic cells (DCs) through multisignaling pathways to trigger potent immune effects. Then, the screened C-25 was used to encapsulate the model peptide antigen, OVA_257–280, to form nanovaccine C-25/OVA_257–280. It was found that the C-25/OVA_257–280 nanovaccine could effectively facilitate DC maturation and antigen cross-presentation without any other additional adjuvant and exhibited excellent prophylactic efficacy in the B16F10-OVA tumor model. Moreover, in combination with antiprogrammed cell death protein-ligand 1 (anti-PD-L1), the C-25/OVA_257–280 nanovaccine could significantly delay the growth of pre-existing tumors. Therefore, this work developed a minimalist nanovaccine with a simple formulation and high efficiency in activating tumor-specific immune responses, showing great potential for further application in cancer immunotherapy.

IF：

18.027

Link：

https://pubs.acs.org/doi/10.1021/acsnano.3c10174