Guo Yunqi, Wang Zhiqiang, Li Gaoming, Zhan Mengsi, Xiao Tingting, Wang Jianhong, van Hest Jan C M, Shi Xiangyang, Shen Mingwu
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, PR China.
Institute of Frontier Medical Technology, College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, PR China.
Bioact Mater. 2024 Sep 23;43:129-144. doi: 10.1016/j.bioactmat.2024.09.024. eCollection 2025 Jan.
Construction of a cancer nanovaccine that can simultaneously activate immune cells and exert efficient tumor treatment still remains a challenge. Herein, we showcase a proof-of-concept demonstration of an advanced therapeutic nanovaccine formulation based on poly(-vinylcaprolactam) nanogels (NGs) which were loaded with manganese dioxide (MnO), the sonosensitizer chlorin e6 (Ce6), and the immune adjuvant cyclic GMP-AMP (cGAMP). The gels were furthermore coated with apoptotic cancer cell membranes (AM). On the one hand, the AM promoted the recognition of NGs by antigen presenting cells (APCs) in lymph nodes due to their enhanced immunogenicity, then the loaded Mn and cGAMP could mature APCs stimulator of interferon genes (STING) activation for triggering immunity to prevent tumor growth. On the other hand, the NGs could selectively release Mn for hydroxyl radical production and Ce6 to generate single oxygen under ultrasound irradiation of tumors, respectively, thereby exerting local chemodynamic/sonodynamic therapy to induce immunogenic cell death (ICD). Moreover, the Mn could also activate STING in tumors to synergize with ICD for potentiated immune responses. Overall, the biomimetic NG-based therapeutic nanovaccine could directly evoke immune system, and also conduct local tumor treatment to further activate ICD, thus realizing a full-cycle immunomodulation (tumor killing for ICD/antigen production, and tumor cells/APCs immune activation) to tackle bilateral tumor growth.
构建一种能够同时激活免疫细胞并实现高效肿瘤治疗的癌症纳米疫苗仍然是一项挑战。在此，我们展示了一种基于聚（乙烯基己内酰胺）纳米凝胶（NGs）的先进治疗性纳米疫苗制剂的概念验证，该纳米凝胶负载了二氧化锰（MnO）、声敏剂二氢卟吩e6（Ce6）和免疫佐剂环磷酸鸟苷 - 腺苷酸（cGAMP）。此外，这些凝胶还用凋亡癌细胞膜（AM）进行了包被。一方面，AM因其增强的免疫原性促进了淋巴结中抗原呈递细胞（APC）对NGs的识别，然后负载的Mn和cGAMP可使APC成熟，刺激干扰素基因（STING）激活以触发免疫来预防肿瘤生长。另一方面，NGs可分别在肿瘤的超声照射下选择性释放Mn以产生羟基自由基和Ce6以产生活性单线态氧，从而进行局部化学动力学/声动力疗法以诱导免疫原性细胞死亡（ICD）。此外，Mn还可激活肿瘤中的STING以与ICD协同作用增强免疫反应。总体而言，这种基于仿生NG的治疗性纳米疫苗可直接激发免疫系统，还能进行局部肿瘤治疗以进一步激活ICD，从而实现全周期免疫调节（肿瘤杀伤产生ICD/抗原，以及肿瘤细胞/APC免疫激活）来应对双侧肿瘤生长。
