Unzippable Siamese Nanoparticles for Programmed Two-Stage Cancer Immunotherapy

  • Adv Mater. 2024 May 29:e2402456. doi: 10.1002/adma.202402456.
Mei Long  1 ,  Yanfeng Zhou  1 ,  Daoxia Guo  1 ,  Qingyun Zhu  2 ,  Huan Liang  1 ,  Xiaoyuan Ji  1 ,  Nan Chen  2 ,  Haiyun Song  1
Affiliations
  • 1. School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 2. College of Chemistry and Materials Science, The Education Ministry Key Lab of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China.
PMID: 38810924 DOI: 10.1002/adma.202402456
Abstract

Epigenetic drugs (epi-drugs) can destruct Cancer cells and initiate both innate and adaptive immunity, yet they have achieved very limited success in solid tumors so far, partly attributing to their concurrent induction of the myeloid-derived suppressor cell (MDSC) population. Here, dissociable Siamese nanoparticles (SIANPs) are developed for tumor cell-targeted delivery of epi-drug CM-272 and MDSC-targeted delivery of small molecule inhibitor Ibrutinib. The SIANPs are assembled via interparticle DNA annealing and detached via tumor microenvironment-triggered strand separation. Such binary regulation induces endogenous retrovirus expression and immunogenic cell death in tumor cells while restraining the immunosuppressive effects of MDSCs, and synergistically promotes dendritic cell maturation and CD8+ T cell activation for tumor inhibition. Significantly, immune microenvironment remodeling via SIANPs further overcomes tumor resistance to immune checkpoint blockade therapy. This study represents a two-pronged approach for orchestrating immune responses, and paves a new way for employing epi-drugs in Cancer Immunotherapy.

Keywords
MDSC reprogramming; Siamese nanoparticles; epigenetic therapy; interparticle DNA reactions; solid tumors.
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