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
Affiliations
Meirong Li
School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China
Jingyu Yang
School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China
Xinhuang Yao
Central Laboratory of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen 518172, China
Xiang Li
School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China
Zhourui Xu
School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China
Shiqi Tang
School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China
Bangxu Sun
Central Laboratory of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen 518172, China
Suxia Lin
Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518048, China
Chengbin Yang
School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China
Jia Liu
Central Laboratory of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen 518172, China
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.
