Combined Immune‐Peptide Nanofiber with HSP70/AKT/mTOR Axis Blockade Enhances Photothermal Immunotherapy, Inhibiting Tumor Growth and Recurrence
8 affiliations
- 1Department of Radiology State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences Beijing China
- 2CAS Key Laboratory of Molecular Imaging Beijing Key Laboratory of Molecular Imaging Institute of Automation Chinese Academy of Sciences Beijing China
- 3School Medical Science and Engineering Beijing Institute of Technology Zhengzhou Academy of Intelligent Technology Beijing Institute of Technology Beijing China
- 4Department of Radiology Peking University People's Hospital Beijing China
- 5Department of Interventional Radiology Shengjing Hospital of China Medical University Shenyang Liaoning China
- 6Laboratory Animal Research Facility National Infrastructures for Translational Medicine Institute of Clinical Medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
- 7Department of Radiation Oncology Shandong Cancer Hospital and Institute Shandong First Medical University Shandong Academy of Medical Sciences Jinan Shandong China
- 8University of Chinese Academy of Sciences Beijing China
Abstract
Although immune checkpoint blockade (ICB) therapies have shown clinical benefit, ICBs exert limited effects on most “immune‐cold” solid tumors, i.e., tumors with low immune infiltration. Photothermal immunotherapy (PTIT) converts “cold” tumors into “hot” tumors, thereby enhancing immune responses and improving ICB efficacy. Hence, developing a strategy that can integrate PTIT and ICB treatment is desirable. In this study, we designed a unique carrier‐free PSP@IR‐CF3 nanofiber, self‐assembled from the programmed death‐ligand 1 (PD‐L1) targeting immune‐peptide NTGYFYGDQ (PSP) and a PTIT agent (IR‐CF3). The nanofibers enable precise tumor targeting and immune checkpoint inhibition by specifically binding to PD‐L1 on the tumor cell surface, also providing an NIR‐mediated photothermal effect. Combining PSP@IR‐CF3 nanofibers with NIR induced mild PTIT, which effectively activated the tumor immune microenvironment and suppressed tumor growth with lower immunotoxicity. Additionally, we identified activation of the heat shock protein 70 (HSP70) /AKT/mTOR axis following PTIT, suggesting a potential role in post‐treatment tumor survival and recurrence. By incorporating the mTOR inhibitor rapamycin, the combination treatment further enhanced therapeutic efficacy and reduced tumor recurrence.
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BibTeX
@article{zhang2026combined,
title = {{Combined Immune‐Peptide Nanofiber with HSP70/AKT/mTOR Axis Blockade Enhances Photothermal Immunotherapy, Inhibiting Tumor Growth and Recurrence}},
author = {Xinyu Zhang and Zhenqi Jiang and Wenjia Zhang and Juncheng Wu and Haozhuo Guo and Changlei Li and Mingwei Sun and Xiaoying Tang and Yue Zhang and Wei Huang and Huadan Xue and Yang Du},
journal = {Advanced Science},
year = {2026},
month = oct,
doi = {10.1002/advs.78434},
url = {https://doi.org/10.1002/advs.78434},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Combined Immune‐Peptide Nanofiber with HSP70/AKT/mTOR Axis Blockade Enhances Photothermal Immunotherapy, Inhibiting Tumor Growth and Recurrence
AU - Xinyu Zhang
AU - Zhenqi Jiang
AU - Wenjia Zhang
AU - Juncheng Wu
AU - Haozhuo Guo
AU - Changlei Li
AU - Mingwei Sun
AU - Xiaoying Tang
AU - Yue Zhang
AU - Wei Huang
AU - Huadan Xue
AU - Yang Du
PY - 2026
DA - 2026/10/25
JO - Advanced Science
DO - 10.1002/advs.78434
UR - https://doi.org/10.1002/advs.78434
AB - Although immune checkpoint blockade (ICB) therapies have shown clinical benefit, ICBs exert limited effects on most “immune‐cold” solid tumors, i.e., tumors with low immune infiltration. Photothermal immunotherapy (PTIT) converts “cold” tumors into “hot” tumors, thereby enhancing immune responses and improving ICB efficacy. Hence, developing a strategy that can integrate PTIT and ICB treatment is desirable. In this study, we designed a unique carrier‐free PSP@IR‐CF3 nanofiber, self‐assembled from the programmed death‐ligand 1 (PD‐L1) targeting immune‐peptide NTGYFYGDQ (PSP) and a PTIT agent (IR‐CF3). The nanofibers enable precise tumor targeting and immune checkpoint inhibition by specifically binding to PD‐L1 on the tumor cell surface, also providing an NIR‐mediated photothermal effect. Combining PSP@IR‐CF3 nanofibers with NIR induced mild PTIT, which effectively activated the tumor immune microenvironment and suppressed tumor growth with lower immunotoxicity. Additionally, we identified activation of the heat shock protein 70 (HSP70) /AKT/mTOR axis following PTIT, suggesting a potential role in post‐treatment tumor survival and recurrence. By incorporating the mTOR inhibitor rapamycin, the combination treatment further enhanced therapeutic efficacy and reduced tumor recurrence.
SN - 2198-3844
ER -