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Publications

Journal Article Ppublish 3 citations

PubMed: 38923327 DOI: 10.1002/advs.202404347

Manipulating the Crosstalk between Cancer and Immunosuppressive Cells with Phototherapeutic Gold-Nanohut for Reprogramming Tumor Microenvironment.

Adv Sci (Weinh) 11(32):e2404347

Authors: Hung-Wei Cheng, Wei Lee, Fei-Ting Hsu, Yen-Ho Lai, Shu-Rou Huang, Chris Seh Hong Lim, Zhen-Kai Lin, Shih-Chao Hsu, Chih-Sheng Chiang, Long-Bin Jeng, Woei-Cherng Shyu, San-Yuan Chen

Affiliations

  • Department of Materials Science and Engineering, National Yang Ming Chiao Tung University, Hsinchu, 30010, Taiwan.
  • Cell Therapy Center, China Medical University Hospital, Taichung, 40447, Taiwan.
  • Department of Biological Science and Technology, China Medical University, Taichung, 406040, Taiwan.
  • Translational Medicine Research Center, New Drug development Center and Department of Neurology, China Medical University Hospital, Taichung, 40447, Taiwan.
  • Department of Physician Assistant Studies, School of Health and Rehabilitation Sciences, MGH Institute, Boston, Massachusetts, 02114, USA.
  • Department of Surgery, China Medical University Hospital, Taichung, 40447, Taiwan.
  • Graduate Institute of Biomedical Science, China Medical University, Taichung, 406040, Taiwan.
  • Neuroscience and Brain Disease Center, China Medical University, Taichung, 40447, Taiwan.
  • Organ Transplantation Center, China Medical University Hospital, Taichung, 40447, Taiwan.
  • School of Medicine, China Medical University, Taichung, 406040, Taiwan.
  • School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.

Abstract

Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer-immunity cycle during treatment. In this study, an anti-PD-L1-immobilized magnetic gold nanohut, AuNH-2-Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH-2-Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH-2-Ab simultaneously target and eliminate cancer cells and tumor-associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH-2-Ab involving the detachment of the surface antibody for in situ PD-L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform.

MeSH

Cells, Biomedical Research, Hyperthermia, Neoplasms, Immunity, Tumor Microenvironment

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