2. Academic Validation
  3. Virus-mimicking nanoparticle potentiates in-situ cancer vaccines by reversing intratumoral DCs via stimulating cytosolic nucleic acid sensors

Virus-mimicking nanoparticle potentiates in-situ cancer vaccines by reversing intratumoral DCs via stimulating cytosolic nucleic acid sensors

  • J Control Release. 2025 Jul 10:383:113801. doi: 10.1016/j.jconrel.2025.113801.
Ya Chu 1,  Luyao Wang 1,  Xi Huang 1,  Cenxi Lao 1,  Lin Luo 1,  Jingyi Chen 1,  Fangfei Jin 1,  Lili Zhao 1,  Kaiyuan Hu 1,  Miao Lv 1,  Xianjing Li 1,  Yong Yang 1,  Weijun Zhao 2,  Wenguang Wang 3
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, China Pharmaceutical University, Nanjing 210009, China; Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing 211198, China.
  • 2 Institute of Translational Medicine, China Pharmaceutical University, Nanjing 210009, China; Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing 211198, China; College of Veterinary Medicine, Nanjing Agricultural University, China.
  • 3 Institute of Translational Medicine, China Pharmaceutical University, Nanjing 210009, China; Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing 211198, China. Electronic address: wgwang@cpu.edu.cn.
PMID: 40339656 DOI: 10.1016/j.jconrel.2025.113801
Abstract

The major challenge for in-situ Cancer vaccines is to activate the dendritic cells (DCs) within the immunosuppressive tumor to initiate tumor-specific immune responses. By contrast, oncolytic viruses can always activate intratumoral DCs to initiate virus-specific immunity to eliminate viruses which will in turn reduce the anti-tumor effect of these viruses. To bridge the two approaches, we developed virus-mimicking nanoparticle (V-mimic) through self-assembly of artificial cyclic gadolinium-based GAMP (c·Gd·GAMP, a STING agonist), double-stranded RNA analog (Poly I:C), and indocyanine green (ICG). Within the V-mimic, c·Gd·GAMP and Poly I:C can simulate the DNA and RNA produced by virus replication to reverse the inhibition of the immunosuppressive tumor microenvironment on DCs by promoting the IFN-β secreting via activating nucleic acid sensors, thereby eliciting anti-tumor immune response in a manner akin to the immune response triggered by viruses. Notably, the V-mimic significantly promoted IFN-β secretion, enhanced DCs maturation, and elicited robust tumor-specific immune memory when combined with photothermal therapy. In multiple tumor models, significant tumor inhibition was observed, including a metastasis and recurrence model. Therefore, leveraging the virus-mimicking nanoparticle to simulate the mechanism of virus-initiated specific immune responses to activate the intratumoral DCs may open up new strategies for in-situ Cancer vaccines.

Keywords

IFN-β; Immune memory; In-situ cancer vaccines; Nucleic acid receptors; Virus-mimicking nanoparticle.

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