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通过单次注射可注射的负载抗原/佐剂的大孔丝素蛋白微球实现高效肿瘤免疫治疗

Efficient Tumor Immunotherapy through a Single Injection of Injectable Antigen/Adjuvant-Loaded Macroporous Silk Fibroin Microspheres.

作者信息

Lei Fang, Cai Jiangfeng, Lyu Ruyin, Shen Honglan, Xu Yalan, Wang Jie, Shuai Yajun, Xu Zongpu, Mao Chuanbin, Yang Mingying

机构信息

Institute of Applied Bioresource Research, College of Animal Science, Zhejiang University, Yuhangtang Road 866, Hangzhou, Zhejiang 310058, P.R. China.

School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, P.R. China.

出版信息

ACS Appl Mater Interfaces. 2022 Sep 28;14(38):42950-42962. doi: 10.1021/acsami.2c11286. Epub 2022 Sep 16.

Abstract

Synthetic or natural materials have been used as vaccines in cancer immunotherapy. However, using them as vaccines necessitates multiple injections or surgical implantations. To tackle such daunting challenges, we develop an injectable macroporous () silk fibroin (SF) microsphere loaded with antigens and immune adjuvants to suppress established tumors with only a single injection. SF microspheres can serve as a scaffold by injection and avoid surgical injury as seen in traditional scaffold vaccines. The macroporous structure of the vaccine facilitates the recruitment of immune cells and promotes the activation of dendritic cells (DCs), resulting in a favorable immune microenvironment that further induces strong humoral and cellular immunity. We have also modified the vaccine into a booster version by simply allowing the antigens to be adsorbed onto the SF microspheres. The booster vaccine highly efficiently suppresses tumor growth by improving the cytotoxic T lymphocyte (CTL) response. In general, these results demonstrate that the macroporous SF microspheres can serve as a facile platform for tumor vaccine therapy in the future. Since the SF microspheres are also potential scaffolds for tissue regeneration, their use as a vaccine platform will enable their applications in eradicating tumors while regenerating healthy tissue to heal the tumor-site cavity.

摘要

合成材料或天然材料已被用作癌症免疫治疗中的疫苗。然而,将它们用作疫苗需要多次注射或手术植入。为应对这些艰巨挑战,我们开发了一种负载抗原和免疫佐剂的可注射大孔丝素蛋白(SF)微球,仅通过单次注射即可抑制已形成的肿瘤。SF微球可通过注射充当支架,避免传统支架疫苗中所见的手术损伤。疫苗的大孔结构有助于免疫细胞的募集并促进树突状细胞(DC)的激活,从而形成有利的免疫微环境,进一步诱导强烈的体液免疫和细胞免疫。我们还通过简单地使抗原吸附到SF微球上,将疫苗改进为加强版。加强疫苗通过改善细胞毒性T淋巴细胞(CTL)反应高效抑制肿瘤生长。总体而言,这些结果表明,大孔SF微球未来可作为肿瘤疫苗治疗的简便平台。由于SF微球也是组织再生的潜在支架,将其用作疫苗平台将使其能够在根除肿瘤的同时应用于再生健康组织以修复肿瘤部位的空洞。

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