Well-Defined Mannosylated Polymer for Peptide Vaccine Delivery with Enhanced Antitumor Immunity.
Well-Defined Mannosylated Polymer for Peptide Vaccine Delivery with Enhanced Antitumor Immunity.
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DOI：
10.1002/adhm.202101651
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发表时间：
2022-05
影响因子：
10
通讯作者：
Pun, Suzie H.
中科院分区：
文献类型：
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作者：
Lv, Shixian;Song, Kefan;Yen, Albert;Peeler, David J.;Nguyen, Dinh Chuong;Olshefsky, Audrey;Sylvestre, Meilyn;Srinivasan, Selvi;Stayton, Patrick S.;Pun, Suzie H.
基于肽的癌症疫苗具有生产和安全优势，但由于其固有的不稳定性、快速清除和低细胞摄取，其临床成功有限。基于纳米颗粒的递送载体可以提高肽抗原的体内稳定性和细胞摄取。在这里，开发了一种明确的自组装甘露糖化聚合物，用于抗癌肽抗原递送。通过RAFT聚合制备两亲性聚合物，肽抗原通过可逆二硫键与pH敏感的疏水性嵌段缀合，在进入细胞后选择性释放。聚合物-肽缀合物在生理 pH 值下自组装成 100 nm 以下的胶束，并在内体 pH 值下解离。甘露糖化的胶束冠增加了引流腹股沟淋巴结中疫苗货物的积累，并促进专业抗原呈递细胞对纳米颗粒的摄取。体内研究表明，与游离肽抗原相比，甘露糖化胶束配方可改善树突状细胞活化并增强抗原特异性 T 细胞反应，从而使荷瘤小鼠具有更高的抗肿瘤免疫力。因此，甘露糖化聚合物是用于递送肽癌症疫苗的简单且有前途的平台。明确的自组装甘露糖基化聚合物提供了多种肽抗原的简单配方，以实现有效的抗肿瘤活性。
Peptide-based cancer vaccines offer production and safety advantages but have had limited clinical success due to their intrinsic instability, rapid clearance, and low cellular uptake. Nanoparticle-based delivery vehicles can improve the in vivo stability and cellular uptake of peptide antigens. Here, a well-defined, self-assembling mannosylated polymer is developed for anti-cancer peptide antigen delivery. The amphiphilic polymer is prepared by RAFT polymerization, and the peptide antigens are conjugated to the pH-sensitive hydrophobic block through the reversible disulfide linkage for selective release after cell entry. The polymer-peptide conjugates self-assemble into sub-100 nm micelles at physiological pH and dissociate at endosomal pH. The mannosylated micellar corona increases the accumulation of vaccine cargoes in the draining inguinal lymph nodes and facilitates nanoparticle uptake by professional antigen presenting cells. In vivo studies demonstrate that the mannosylated micelle formulation improved dendritic cell activation and enhanced antigen-specific T cell responses, resulting in higher antitumor immunity in tumor-bearing mice compared to free peptide antigen. The mannosylated polymer is therefore a simple and promising platform for the delivery of peptide cancer vaccines. A well-defined, self-assembling mannosylated polymer provides straightforward formulation of multiple peptide antigens for effective anti-tumor activity.
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影响因子：
38.3
作者：
Luo M;Wang H;Wang Z;Cai H;Lu Z;Li Y;Du M;Huang G;Wang C;Chen X;Porembka MR;Lea J;Frankel AE;Fu YX;Chen ZJ;Gao J
通讯作者：
Gao J
影响因子：
4
作者：
Hogervorst, Tim P.;Li, R. J. Eveline;Codee, Jeroen D. C.
通讯作者：
Codee, Jeroen D. C.
影响因子：
16.6
作者：
Cheng, Yilong;Yumul, Roma C.;Pun, Suzie H.
通讯作者：
Pun, Suzie H.
影响因子：
15.9
作者：
Hanson, Melissa C.;Crespo, Monica R.;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.
影响因子：
64.8
作者：
通讯作者：
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