A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy
A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy
复制标题
基于光响应纳米颗粒的递送系统，使用脱镁叶绿酸 A 移植物聚乙烯亚胺用于基于树突状细胞的癌症免疫治疗
DOI：
10.1021/acs.molpharmaceut.7b00015
复制
发表时间：
2017
影响因子：
4.9
通讯作者：
Chen Li
中科院分区：
文献类型：
--
作者：
Chuangnian Zhang;Ju Zhang;Gaona Shi;Huijuan Song;Shengbin Shi;Xiuyuan Zhang;Pingsheng Huang;Zhihong Wang;Weiwei Wang;Chun Wang;Deling Kong;Chen Li
在这项研究中，光化学内化（PCI）技术被采用在基于纳米颗粒的抗原递送系统中，以增强用于癌症免疫治疗的抗原特异性CD 8 + T细胞免疫应答。制备了具有核内体逃逸活性和近红外成像能力的疏水光敏剂脱镁叶绿酸A（PheoA-PEI）。然后将模型抗原卵清蛋白（OVA）与PheoA-PEI复合以形成对光响应的PheoA-PEI/OVA纳米颗粒（PheoA-PEI/OVA NP）。流式细胞术分析显示，与游离OVA相比，用PheoA-PEI/OVA NP处理的鼠树突状细胞系（DC 2.4）中的内吞作用增加。DC2.4细胞中活性氧（ROS）的产生也使用2 '，7'-二氯二氢荧光素二乙酸酯（DCFH-DA）定量和定性地证实。共聚焦激光扫描显微镜（CLSM）进一步证明，PheoA-PEI/OVA NP在光刺激后增强胞质抗原释放。此外，PheoA-PEI/OVA NP处理的DC 2.4细胞在体外光照射后表现出增强的对B3 Z T细胞杂交瘤的交叉呈递，与用游离OVA处理的那些相比显著增加。一致地，体内结果显示用树突状细胞加PheoA-PEI/OVA NP和光照射处理的小鼠肿瘤中的CD 3 + CD 8 +T淋巴细胞上调。活化的T细胞应答部分负责树突状细胞加PheoA-PEI/OVA NP和光照射免疫的小鼠中对E.G7肿瘤生长的抑制作用。我们的研究结果证明了通过基于光响应纳米颗粒的疫苗递送用于癌症免疫治疗来增强抗原特异性CD 8 + T细胞免疫应答的可行性。
In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8+ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape activity and near-infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light. Flow cytometry analysis revealed increased endocytosis in a murine dendritic cell line (DC2.4) that was treated with PheoA-PEI/OVA NPs compared to free OVA. Generation of reactive oxygen species (ROS) in DC2.4 cells was also confirmed quantitatively and qualitatively using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Confocal laser scanning microscopy (CLSM) further demonstrated that the PheoA-PEI/OVA NPs enhanced cytosolic antigen release after light stimulation. Moreover, PheoA-PEI/OVA NP treated DC2.4 cells exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro after light irradiation, substantially increased compared to those treated with free OVA. Consistently, in vivo results revealed upregulation of CD3+CD8+T lymphocytes in tumors of mice treated with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. The activated T cell response is partly responsible for the inhibitory effect on E.G7 tumor growth in mice immunized with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. Our results demonstrate the feasibility to enhance antigen-specific CD8+ T cell immune response by light-responsive nanoparticle-based vaccine delivery for cancer immunotherapy.