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已发表论文
基于活性氧疗法的纳米级金丝桃素诱导免疫细胞死亡研究进展：微型综述
Received 9 September 2025
Accepted for publication 29 November 2025
Published 9 December 2025 Volume 2025:20 Pages 14695—14705
DOI https://doi.org/10.2147/IJN.S566489
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. RDK Misra
Chuanshan Xu,1,* Xiaowen Cai,2,* Lingran Du1
1Key Laboratory of Molecular Target and Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 2School of Applied Biology, Shenzhen City Polytechnic, Shenzhen, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lingran Du, Key Laboratory of Molecular Target and Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China, Tel/Fax +8620-37106238, Email dulingran@126.com
Abstract: Immunotherapy is emerging as a powerful strategy against cancer; however, its efficacy is often blunted by the immunosuppressive tumor microenvironment (TME). Immunogenic cell death (ICD) can tilt this balance by releasing tumor-associated antigens and damage-associated molecular patterns that enhance TME immunogenicity, promote antigen-presenting cell maturation, and activate effector T cells. Ionizing radiation and doxorubicin (Dox) are two types of the common ICD inducers. However, they have severe off-target toxicities and limited therapeutic indices. To overcome these challenges, safe and natural products are now drawing widespread attention. Hypericin, a naturally occurring photosensitizer derived from the traditional Chinese herb Hypericum perforatum (St. John’s wort), has been used medicinally for centuries, and is now recognized for its potent antimicrobial, antiviral, anti-inflammatory, and anticancer properties. Recent studies have revealed that hypericin can modulate tumor immunity, and when employed in photodynamic therapy (PDT) or sonodynamic therapy (SDT) it generates reactive oxygen species that trigger endoplasmic reticulum stress-mediated ICD. Nanocarrier-mediated delivery further amplified these effects by enhancing hypericin solubility, tumor accumulation, and ROS yield upon light irradiation. This minireview synthesizes the current knowledge on the immunomodulatory actions of hypericin within the tumor microenvironment, evaluates its performance as a PDT/SDT-based ICD inducer, and highlights that nanosized formulations of hypericin may accelerate the development of novel ICD inducers and immunomodulators.
Keywords: hypericin, photodynamic therapy, sonodynmamic therapy, nanosizing technology, immunogenic cell death, tumor immune microenvironment, cancer immunotherapy
1Key Laboratory of Molecular Target and Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 2School of Applied Biology, Shenzhen City Polytechnic, Shenzhen, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lingran Du, Key Laboratory of Molecular Target and Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China, Tel/Fax +8620-37106238, Email dulingran@126.com
Abstract: Immunotherapy is emerging as a powerful strategy against cancer; however, its efficacy is often blunted by the immunosuppressive tumor microenvironment (TME). Immunogenic cell death (ICD) can tilt this balance by releasing tumor-associated antigens and damage-associated molecular patterns that enhance TME immunogenicity, promote antigen-presenting cell maturation, and activate effector T cells. Ionizing radiation and doxorubicin (Dox) are two types of the common ICD inducers. However, they have severe off-target toxicities and limited therapeutic indices. To overcome these challenges, safe and natural products are now drawing widespread attention. Hypericin, a naturally occurring photosensitizer derived from the traditional Chinese herb Hypericum perforatum (St. John’s wort), has been used medicinally for centuries, and is now recognized for its potent antimicrobial, antiviral, anti-inflammatory, and anticancer properties. Recent studies have revealed that hypericin can modulate tumor immunity, and when employed in photodynamic therapy (PDT) or sonodynamic therapy (SDT) it generates reactive oxygen species that trigger endoplasmic reticulum stress-mediated ICD. Nanocarrier-mediated delivery further amplified these effects by enhancing hypericin solubility, tumor accumulation, and ROS yield upon light irradiation. This minireview synthesizes the current knowledge on the immunomodulatory actions of hypericin within the tumor microenvironment, evaluates its performance as a PDT/SDT-based ICD inducer, and highlights that nanosized formulations of hypericin may accelerate the development of novel ICD inducers and immunomodulators.
Keywords: hypericin, photodynamic therapy, sonodynmamic therapy, nanosizing technology, immunogenic cell death, tumor immune microenvironment, cancer immunotherapy