State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China; Shenzhen Institute of Translational Medicine, Health Science Center, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100190, China.
Biomaterials. 2022 Jan;280:121313. doi: 10.1016/j.biomaterials.2021.121313. Epub 2021 Dec 7.
While research on cancer vaccines has made great strides in the field of immunotherapy, the targeted delivery of multiple effective components (rational-tailored antigens and adjuvants) remains a challenge. Here, we utilized the unique hierarchical structures of Pickering emulsions (particles, oil core, and water-oil interface) to develop mannosylated (M) Pickering emulsions (PE) that target antigen presenting cells and synergistically deliver antigenic peptides and the TLR9 agonist CpG (C) as an enhanced cancer vaccine (MPE-C). We chemically linked mannose residues to PLGA/PLAG-PEG nanoparticles and produced a dense array of mannose on the nanopatterned surface of Pickering emulsions, allowing for increased cellular targeting. Together with the inherent deformability of the oily core, MPE-C increased the droplet-cellular contact area and provoked the cellular recognition of mannose and CpG for enhanced immune activation. We found that MPE-C attracted a large number of APCs to the local site of administration, evidently increasing cellular uptake and activation. Additionally, we observed increased antigen-specific cellular immune responses, with potent anti-tumor effects against both E.G7-OVA and B16-MUCI tumors. Furthermore, MPE-C combined with PD-1 antibodies produced a significant tumor regression, resulting in synergistic increases in anti-tumor effects. Thus, through the strategic loading of mannose, antigens, and CpG, Pickering emulsions could serve as a targeted delivery platform for enhanced multicomponent cancer vaccines.
虽然癌症疫苗的研究在免疫疗法领域取得了重大进展，但如何靶向递多种有效成分（合理设计的抗原和佐剂）仍然是一个挑战。在这里，我们利用 Pickering 乳液（颗粒、油核和油水界面）的独特分层结构，开发了靶向抗原呈递细胞的甘露糖化（M）Pickering 乳液（PE），并协同递呈抗原肽和 TLR9 激动剂 CpG（C）作为增强型癌症疫苗（MPE-C）。我们将甘露糖残基化学连接到 PLGA/PLAG-PEG 纳米颗粒上，并在 Pickering 乳液的纳米图案化表面上产生密集的甘露糖排列，从而增加细胞靶向性。结合油核的固有可变形性，MPE-C 增加了液滴-细胞接触面积，并引发细胞对甘露糖和 CpG 的识别，从而增强免疫激活。我们发现 MPE-C 吸引大量 APC 到局部给药部位，明显增加了细胞摄取和激活。此外，我们观察到抗原特异性细胞免疫反应增强，对 E.G7-OVA 和 B16-MUCI 肿瘤均具有强大的抗肿瘤作用。此外，MPE-C 与 PD-1 抗体联合使用可显著抑制肿瘤生长，协同增强抗肿瘤作用。因此，通过对甘露糖、抗原和 CpG 的策略性加载，Pickering 乳液可以作为增强型多组分癌症疫苗的靶向递药平台。
