Modified hollow mesoporous silica nanoparticles as immune adjuvant-nanocarriers for photodynamically enhanced cancer immunotherapy.
Modified hollow mesoporous silica nanoparticles as immune adjuvant-nanocarriers for photodynamically enhanced cancer immunotherapy.
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改性中空介孔二氧化硅纳米粒子作为免疫清除剂纳米载体用于光动力学增强的癌症免疫治疗。
DOI：
10.3389/fbioe.2022.1039154
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发表时间：
2022
影响因子：
5.7
通讯作者：
Tao, Juan
中科院分区：
文献类型：
--
作者：
Li, Qianru;Liu, Qianqian;Li, Heli;Dong, Liyun;Zhou, Yajie;Zhu, Jintao;Yang, Liu;Tao, Juan
关键词：
纳米医学在加强肿瘤免疫治疗方面显示出巨大的潜力。然而，基于纳米粒(NP)的免疫治疗在诱导有效的抗肿瘤反应和抑制肿瘤转移方面仍存在局限性。因此，将聚乙烯亚胺(PEI)杂化薄壳中空介孔二氧化硅纳米颗粒(THMSN)作为佐剂-纳米载体，并包裹极少量的光敏剂氯e6(Ce6)，以实现光动力疗法(PDT)/免疫治疗的协同作用。通过PEI刻蚀，得到的Ce6@THMSN表现出增强的细胞内化和内小体/溶酶体逃逸，从而进一步提高了Ce6@THMSN对肿瘤细胞的PDT杀伤效果。PDT治疗后，以THMSN为佐剂释放的肿瘤相关抗原促进树突状细胞成熟，进一步促进CD8+细胞毒性T淋巴细胞活化，触发抗肿瘤免疫反应。体内实验表明，基于Ce6@THMSN的PDT在消除原发肿瘤和诱导持久的肿瘤特异性免疫反应方面具有显著的效力，从而防止远处转移。因此，我们提供了一种THMSNS介导和PDT触发的具有免疫原性的纳米治疗系统，该系统可以诱导强大的抗肿瘤免疫，并有望在未来的免疫治疗的临床应用中发挥作用。
Nanomedicine has demonstrated great potential in enhancing cancer immunotherapy. However, nanoparticle (NP)-based immunotherapy still has limitations in inducing effective antitumor responses and inhibiting tumor metastasis. Herein, polyethylenimine (PEI) hybrid thin shell hollow mesoporous silica NPs (THMSNs) were applied as adjuvant-nanocarriers and encapsulated with very small dose of photosensitizer chlorine e6 (Ce6) to realize the synergy of photodynamic therapy (PDT)/immunotherapy. Through PEI etching, the obtained Ce6@THMSNs exhibited enhanced cellular internalization and endosome/lysosome escape, which further improved the PDT efficacy of Ce6@THMSNs in destroying tumor cells. After PDT treatment, the released tumor-associated antigens with the help of THMSNs as adjuvants promoted dendritic cells maturation, which further boosted CD8+ cytotoxic T lymphocytes activation and triggered antitumor immune responses. The in vivo experiments demonstrated the significant potency of Ce6@THMSNs-based PDT in obliterating primary tumors and inducing persistent tumor-specific immune responses, thus preventing distant metastasis. Therefore, we offer a THMSNs-mediated and PDT-triggered nanotherapeutic system with immunogenic property, which can elicit robust antitumor immunity and is promising for future clinical development of immunotherapy.
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