Ji Ying, Zhao Jihui, Chu Chih-Chang
Department of Fiber Science and Apparel Design, Cornell University, Ithaca, New York 14853-4401, USA.
J Mater Chem B. 2018 Apr 7;6(13):1930-1942. doi: 10.1039/c7tb03233a. Epub 2018 Mar 14.
The generation of CD8 T cells is crucial in adaptive immunity against cancer and many infectious diseases. Vaccines aimed to stimulate CD8 T cell response typically become ineffective because the antigens are subject to sequestration in endocytic compartments, instead of being delivered cytosolically for MHC-I processing and presentation. In this study, a nano-carrier (Arg-Phe-PEA(AP) nanoparticles) for ovalbumin (OVA) was developed from arginine- and phenylalanine-based poly(ester amide)s, which further formed an electrostatic complex with AlPcS2a, a typical photosensitizer for photochemical internalization (PCI) strategies. The nanocarrier significantly enhanced the internalization efficiency by dendritic cells of both OVA and AlPcS2a. The photochemical interruption of endocytic compartments by the AlPcS2a photosensitizer complexed in the nanocarrier enabled the light-facilitated endosomal escape of OVA. MHC-I presentation and CD8 T cell response were elicited by OVA-loaded Arg-Phe-PEA(AP) nanoparticles when light irradiation was applied at 660 nm. The light-facilitated delivery of OVA was dependent on the light dose and the concentration of the photosensitizer, both in vitro and in vivo. The optimized stimulation of MHC-I response demonstrated the potency of this light-facilitated nano-platform for CD8 T cell-inducing vaccination.
CD8 T细胞的产生在针对癌症和许多传染病的适应性免疫中至关重要。旨在刺激CD8 T细胞反应的疫苗通常会失效，因为抗原会被隔离在内吞小室中，而不是被胞质递送用于MHC-I加工和呈递。在本研究中，由基于精氨酸和苯丙氨酸的聚（酯酰胺）开发了一种用于卵清蛋白（OVA）的纳米载体（精氨酸-苯丙氨酸-PEA（AP）纳米颗粒），其进一步与AlPcS2a形成静电复合物，AlPcS2a是光化学内化（PCI）策略的典型光敏剂。该纳米载体显著提高了OVA和AlPcS2a被树突状细胞内化的效率。纳米载体中复合的AlPcS2a光敏剂对胞吞小室的光化学破坏使得OVA能够通过光促进从内体逃逸。当在660 nm波长进行光照时，负载OVA的精氨酸-苯丙氨酸-PEA（AP）纳米颗粒引发了MHC-I呈递和CD8 T细胞反应。在体外和体内，OVA的光促进递送均取决于光剂量和光敏剂浓度。对MHC-I反应的优化刺激证明了这种光促进纳米平台在诱导CD8 T细胞疫苗接种方面的效力。
