Trp2 Peptide-Assembled Nanoparticles with Intrinsically Self-Chelating 64Cu Properties for PET Imaging Tracking and Dendritic Cell-Based Immunotherapy against Melanoma
Trp2 Peptide-Assembled Nanoparticles with Intrinsically Self-Chelating 64Cu Properties for PET Imaging Tracking and Dendritic Cell-Based Immunotherapy against Melanoma
复制标题
具有内在自螯合 64Cu 特性的 Trp2 肽组装纳米颗粒，用于 PET 成像跟踪和基于树突状细胞的黑色素瘤免疫治疗
DOI：
10.1021/acsabm.1c00480
复制
发表时间：
2021-06-16
影响因子：
4.7
通讯作者：
Gao, Fuping
中科院分区：
文献类型：
--
作者：
He, Zhesheng;Jia, Huiju;Gao, Fuping
基于树突状细胞的免疫治疗是将抗原有效地递送至树突状细胞，然后由抗原刺激的树突状细胞迁移至引流淋巴结（DLN）以诱导CD 8（+）T细胞免疫应答，显示了肿瘤免疫治疗的巨大前景。在这项研究中，我们使用由Trp 2抗原和短链聚乙二醇（PEG）和焦脱镁叶绿酸-A（PPa）的缀合物（Trp 2/PPa-PEGm）形成的共组装纳米颗粒将Trp 2递送到DC。自螯合Cu-64的共组装体可用于通过正电子发射断层扫描（PET）成像灵敏地成像DC在体内的迁移。Trp 2抗原的共组装体被DC有效地吞噬，而不引起DC的体外细胞毒性，并诱导DC成熟。注射Trp 2抗原共组装体标记的DC后，PET成像可灵敏地观察到DC在体内向DLN的归巢。注射含有Trp 2/PPa-PEGm NP的DC的C57 BL/6小鼠显示抗原特异性免疫应答，包括增强的干扰素-γ（IFN-γ）产生、脾细胞增殖和分泌IFN-γ的CD 8（+）T细胞的百分比。此外，接种B16-F10肿瘤细胞的C57 BL/6小鼠在用Trp 2/PPa-PEGm NP标记的DC疫苗免疫后显示肿瘤生长延迟，并且肿瘤中的CD 8（+）T细胞浸润增强。
Dendritic cell-based immunotherapy, in which the antigen is effectively delivered to dendritic cells and then the dendritic cells stimulated by the antigen migrate to draining lymph nodes (DLNs) to induce the CD8(+) T-cell immune response, shows great promise for tumor immunotherapy. In this study, we used coassembled nanoparticles formed by Trp2 antigen and the conjugates of short-chain poly(ethylene glycol) (PEG) and pyropheophorbide-A (PPa) (Trp2/PPa-PEGm) to deliver Trp2 to DCs. Intrinsically self-chelating Cu-64 of coassemblies could be used to sensitively image the migration of DCs in vivo by positron emission tomography (PET) imaging. The coassemblies of the Trp2 antigen were efficiently engulfed by DCs without causing DC cytotoxicity in vitro and induced DC maturation. After injection of DCs labeled by coassemblies of the Trp2 antigen, the homing of DCs to DLNs in vivo could be sensitively observed by PET imaging. The C57BL/6 mice injected with DCs containing the Trp2/PPa-PEGm NP showed antigen-specific immune responses including enhanced interferon-gamma (IFN-gamma) production, splenocyte proliferation, and percentage of IFN-gamma-secreting CD8(+) T cells. In addition, C57BL/6 mice inoculated with B16-F10 tumor cells showed delayed tumor growth after immunization with the Trp2/PPa-PEGm NP-labeled DC vaccine and enhanced infiltration of CD8(+) T cells in tumors.