2. Academic Validation
  3. A photodynamic nanohybrid system reverses hypoxia and augment anti-primary and metastatic tumor efficacy of immunotherapy

A photodynamic nanohybrid system reverses hypoxia and augment anti-primary and metastatic tumor efficacy of immunotherapy

  • Acta Pharm Sin B. 2025 Jun;15(6):3243-3258. doi: 10.1016/j.apsb.2025.04.007.
Haitao Yuan 1,  Xiaoxian Wang 2,  Xin Sun 1,  Di Gu 3 4,  Jinan Guo 1 4,  Wei Huang 5,  Jingbo Ma 1,  Chunjin Fu 1,  Da Yin 1,  Guohua Zeng 3 4,  Ying Long 2,  Jigang Wang 1 3 6 7,  Zhijie Li 1
Affiliations

Affiliations

  • 1 Department of Cardiology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.
  • 2 Department of Hyperbaric Oxygen Medicine, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, China.
  • 3 Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China.
  • 4 Department of Urology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.
  • 5 School of Chemical Engineering and Technology, Sun Yat-sen University, Zhuhai 519082, China.
  • 6 State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China.
  • 7 State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
PMID: 40654337 DOI: 10.1016/j.apsb.2025.04.007
Abstract

Photodynamic immunotherapy is a promising strategy for Cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the Anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II Reactive Oxygen Species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Keywords

Cancer therapy; Checkpoint blockades; Hypoxia; Immunogenic cell death; Photodynamic immunotherapy; Reactive oxygen species; Tumor microenvironment; Vascular normalization.

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