IF 19! A Transformable Trifecta Nanovaccine Responsive to the Tumor Microenvironment Enhances Anti-Tumor Immunity

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In situ tumor vaccines (ISTVs) have great potential in tumor immunotherapy, but three major obstacles still need to be overcome, including insufficient endogenous antigen uptake by dendritic cells (DCs), weak T cell immune responses, and the persistence of a stubbornly immunosuppressive tumor microenvironment (TME).Here, a triple nanovaccine (TriNV) with TME-responsive convertible capability was developed to triple enhance anti-tumor immunity. First, after inducing immunogenic cell death via TriNV-based phot immunotherapy, sufficient endogenous tumor-associated antigens (TAAs) are released in situ. In the TME, the soft-convertible TriNV enhances DC uptake of TAAs, thereby boosting adaptive immunity.Secondly, self-regulated TriNV and Mn²⁺ released in response to TME synergistically promote DC maturation and macrophage M1 polarization by enhancing stimuli that activate interferon genes, thereby further amplifying T cell immune responses.In addition, the decomposition of MnO₂ at the core of TriNV depletes glutathione and promotes the release of O₂ to alleviate hypoxia in the TME, thereby overcoming the chemical barriers of the TME and further reducing immunosuppression. As a result, TriNV significantly eradicates primary tumors and inhibits distant metastasis, demonstrating the great potential of this ISTV nanoplatform as a feasible and effective approach to combat poorly immunogenic solid tumors.

Original link

Boosting Antitumor Immunity via a Tumor Microenvironment-Responsive Transformable Trifecta Nanovaccine
Advanced Functional Materials ( IF 19 )

Pub Date : 2024-01-09

DOI: 10.1002/adfm.202311480

Qiang Li,  Meng Dang,  Jun Tao,  Xiaoye Li,  Weijun Xiu,  Zhuo Dai,  Ao He, MengDing,  Yu Zhang,  Zhi‐fa Wen,  Xiaodan Su,  Aaron James Elbourne,  Lei Bao,Lin Chen,  Yongbin Mou,  Zhaogang Teng,  Heng Dong