Pharmaceutics (Mar 2023)

Multifunctional Mesoporous Silica-Coated Gold Nanorods Mediate Mild Photothermal Heating-Enhanced Gene/Immunotherapy for Colorectal Cancer

  • Meirong Li,
  • Jingyu Yang,
  • Xinhuang Yao,
  • Xiang Li,
  • Zhourui Xu,
  • Shiqi Tang,
  • Bangxu Sun,
  • Suxia Lin,
  • Chengbin Yang,
  • Jia Liu

DOI
https://doi.org/10.3390/pharmaceutics15030854
Journal volume & issue
Vol. 15, no. 3
p. 854

Abstract

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Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths in the world. It is urgent to search for safe and effective therapies to address the CRC crisis. The siRNA-based RNA interference targeted silencing of PD-L1 has extensive potential in CRC treatment but is limited by the lack of efficient delivery vectors. In this work, the novel cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs)/siPD-L1 co-delivery vectors AuNRs@MS/CpG ODN@PEG-bPEI (ASCP) were successfully prepared by two-step surface modification of CpG ODNs-loading and polyethylene glycol-branched polyethyleneimine-coating around mesoporous silica-coated gold nanorods. ASCP promoted dendritic cells (DCs) maturation by delivering CpG ODNs, exhibiting excellent biosafety. Next, mild photothermal therapy (MPTT) mediated by ASCP killed tumor cells and released tumor-associated antigens, further promoting DC maturation. Furthermore, ASCP exhibited mild photothermal heating-enhanced performance as gene vectors, resulting in an increased PD-L1 gene silencing effect. Enhanced DCs maturity and enhanced PD-L1 gene silencing significantly promoted the anti-tumor immune response. Finally, the combination of MPTT and mild photothermal heating-enhanced gene/immunotherapy effectively killed MC38 cells, leading to strong inhibition of CRC. Overall, this work provided new insights into the design of mild photothermal/gene/immune synergies for tumor therapy and may contribute to translational nanomedicine for CRC treatment.

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