Polyethylenimine Hybrid Thin-Shell Hollow Mesoporous Silica Nanoparticles as Vaccine Self-Adjuvants for Cancer Immunotherapy
Polyethylenimine Hybrid Thin-Shell Hollow Mesoporous Silica Nanoparticles as Vaccine Self-Adjuvants for Cancer Immunotherapy
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DOI：
10.1021/acsami.9b19446
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发表时间：
2019-12-25
影响因子：
9.5
通讯作者：
Tao, Juan
中科院分区：
文献类型：
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作者：
Liu, Qianqian;Zhou, Yajie;Tao, Juan
常规佐剂（例如，铝）不足以触发细胞介导的免疫，而细胞介导的免疫在触发针对癌症的特异性免疫中起着至关重要的作用。因此，为癌症疫苗开发合适的佐剂是刺激抗肿瘤免疫应答的中心途径。中空介孔二氧化硅纳米颗粒（HMSNs）已被证明在体内刺激Th1抗肿瘤免疫并在新型癌症疫苗的配制中促进免疫记忆。然而，现有HMSN对抗癌免疫的免疫应答率仍然很低。在这里，我们展示了通过用于癌症免疫治疗的简易PEI蚀刻策略产生聚乙烯亚胺（PEI）掺入的薄壳HMSNs（THMSNs）。有趣的是，加入PEI和THMSNs的薄壳中空结构不仅提高了抗原负载功效和药物持续释放特性，而且增强了DC的吞噬效率，使DC成熟和Th 1免疫，并维持免疫记忆，从而增强THMSNs的佐剂作用。此外，THMSNs疫苗无明显副作用，可分别在肿瘤攻击和再攻击模型中显著降低肿瘤生长和转移的潜力。THMSNs被认为是用于配制用于免疫治疗的癌症疫苗的有前途的载体和优良佐剂。
Conventional adjuvants (e.g., aluminum) are insufficient to trigger cell-mediated immunity, which plays a crucial role in triggering specific immunity against cancer. Therefore, developing appropriate adjuvants for cancer vaccines is a central way to stimulate the antitumor immune response. Hollow mesoporous silica nanoparticles (HMSNs) have been proven to stimulate Th1 antitumor immunity in vivo and promote immunological memory in the formulation of novel cancer vaccines. Yet, immune response rates of existing HMSNs for anticancer immunity still remain low. Here, we demonstrate the generation of polyethylenimine (PEI)-incorporated thinshell HMSNs (THMSNs) through a facile PEI etching strategy for cancer immunotherapy. Interestingly, incorporation of PEI and thin-shell hollow structures of THMSNs not only improved the antigen-loading efficacy and sustained drug release profiles but also enhanced the phagocytosis efficiency by dendritic cells (DCs), enabled DC maturation and Thl immunity, and sustained immunological memory, resulting in the enhancement of the adjuvant effect of THMSNs. Moreover, THMSNs vaccines without significant side effects can significantly reduce the potentiality of tumor growth and metastasis in tumor challenge and rechallenge models, respectively. THMSNs are considered to be promising vehicles and excellent adjuvants for the formulation of cancer vaccines for immunotherapy.