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Photoresponsive Polypeptide-Glycosylated Dendron Amphiphiles: UV-Triggered Polymersomes, OVA Release, and In Vitro Enhanced Uptake and Immune Response
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-12-02 , DOI: 10.1021/acs.biomac.0c01465 Yingying Song 1 , Yanzheng Chen 1 , Pan Li 1 , Chang-Ming Dong 1
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-12-02 , DOI: 10.1021/acs.biomac.0c01465 Yingying Song 1 , Yanzheng Chen 1 , Pan Li 1 , Chang-Ming Dong 1
Affiliation
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Efficient therapeuic proteins’ delivery into mammalian cells and subcellular transport (e.g., fast escape from endolysosomes into cytoplasm) are two key biological barriers that need to be overcome for antigen-based immunotherapy and related biomedical applications. For those purposes, we designed a novel kind of photoresponsive polypeptide-glycosylated poly(amidoamine) (PAMAM) dendron amphiphiles (PGDAs), and their synthesis, UV-responsive self-assembly, and triggered ovalbumin (OVA) release have been fully investigated. The highly anisotropic PGDA4 with a glycosylated second-generation PAMAM dendron self-assembled into stable polypeptide vesicles (polymersomes) within 20–50 wt % water, which exhibited UV-responsive reassembly, dynamic binding with a lectin of concanavalin A, and an accelerated OVA release in vitro. Moreover, upon 365 nm UV irradiation, the self-assembled polymersomes of those glycopolypeptides were transformed into micellar aggregates in aqueous solution at pH 7.4 but disassembled completely at pH 5. The OVA-loaded polymersomes could efficiently deliver OVA into RAW264.7 cells and achieve enhanced endolysosomes escape upon UV irradiation, as revealed by flow cytometry and confocal laser scanning microscopy (CLSM). Furthermore, the enzyme-linked immunosorbent assay (ELISA) showed that the blank sugar-coated polypeptidosomes activated a high level of tumor necrosis factor α (TNF-α) of 468 pg/mL, playing a better role of immune adjuvant for activating the macrophages. Upon the UV irradiation with a dose of 3 J/cm2, the OVA-loaded polymersomes could further stimulate RAW264.7 and enhance the TNF-α level by about 45%. Consequently, this work provides a versatile platform to construct photosensitive and sugar-coated polymersomes of glycopolypeptides that have potential applications for protein delivery, immune adjuvant, and antigen-based immunotherapy.
中文翻译：
光敏多肽糖基化的Dendron两亲物：紫外线触发的聚合物小体，OVA释放和体外增强的摄取和免疫反应。
有效的治疗性蛋白质向哺乳动物细胞的传递和亚细胞运输（例如，从溶酶体快速逃逸到细胞质中）是基于抗原的免疫治疗和相关生物医学应用需要克服的两个关键生物障碍。出于这些目的，我们设计了一种新型的光响应多肽-糖基化聚（酰胺基胺）（PAMAM）树突两亲物（PGDA），并对其合成，紫外线响应自组装和触发的卵清蛋白（OVA）释放进行了充分研究。高度各向异性的PGDA 4糖基化的第二代PAMAM树突在20–50 wt％的水中自组装成稳定的多肽囊泡（多聚体），表现出紫外线响应性重组，与伴刀豆球蛋白A的凝集素动态结合，并在体外加速OVA释放。此外，在365 nm紫外线照射下，这些糖多肽的自组装多聚体在pH 7.4的水溶液中转变成胶束聚集体，但在pH 5时完全分解。负载OVA的多聚体可有效地将OVA递送至RAW264.7细胞并实现流式细胞仪和共聚焦激光扫描显微镜（CLSM）揭示，增强的溶酶体在紫外线照射下会逸出。此外，酶联免疫吸附试验（ELISA）表明，空白糖衣被覆的多肽小体激活了468 pg / mL的高水平的肿瘤坏死因子α（TNF-α），在免疫佐剂中激活了巨噬细胞。紫外线照射后剂量为3 J / cm如图2所示，负载OVA的聚合物小体可以进一步刺激RAW264.7并使TNF-α水平提高约45％。因此，这项工作为构建糖多肽的光敏和糖衣多聚体提供了一个通用平台，这些糖体在蛋白质递送，免疫佐剂和基于抗原的免疫治疗方面具有潜在的应用。
更新日期：2020-12-14
中文翻译：
光敏多肽糖基化的Dendron两亲物：紫外线触发的聚合物小体，OVA释放和体外增强的摄取和免疫反应。
有效的治疗性蛋白质向哺乳动物细胞的传递和亚细胞运输（例如，从溶酶体快速逃逸到细胞质中）是基于抗原的免疫治疗和相关生物医学应用需要克服的两个关键生物障碍。出于这些目的，我们设计了一种新型的光响应多肽-糖基化聚（酰胺基胺）（PAMAM）树突两亲物（PGDA），并对其合成，紫外线响应自组装和触发的卵清蛋白（OVA）释放进行了充分研究。高度各向异性的PGDA 4糖基化的第二代PAMAM树突在20–50 wt％的水中自组装成稳定的多肽囊泡（多聚体），表现出紫外线响应性重组，与伴刀豆球蛋白A的凝集素动态结合，并在体外加速OVA释放。此外，在365 nm紫外线照射下，这些糖多肽的自组装多聚体在pH 7.4的水溶液中转变成胶束聚集体，但在pH 5时完全分解。负载OVA的多聚体可有效地将OVA递送至RAW264.7细胞并实现流式细胞仪和共聚焦激光扫描显微镜（CLSM）揭示，增强的溶酶体在紫外线照射下会逸出。此外，酶联免疫吸附试验（ELISA）表明，空白糖衣被覆的多肽小体激活了468 pg / mL的高水平的肿瘤坏死因子α（TNF-α），在免疫佐剂中激活了巨噬细胞。紫外线照射后剂量为3 J / cm如图2所示，负载OVA的聚合物小体可以进一步刺激RAW264.7并使TNF-α水平提高约45％。因此，这项工作为构建糖多肽的光敏和糖衣多聚体提供了一个通用平台，这些糖体在蛋白质递送，免疫佐剂和基于抗原的免疫治疗方面具有潜在的应用。
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