A Minireview on Nanosized Hypericin-Based Inducer of Immune Cell Death Under ROS-Based Therapies

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Cancer immunotherapy efficacy is limited by the immunosuppressive tumor microenvironment (TME).
• Immunogenic cell death (ICD) can enhance anti-tumor immunity by releasing tumor antigens and danger signals.
• Conventional ICD inducers like radiation and doxorubicin have significant toxicities.

Purpose of the Study:

• To review the immunomodulatory effects of hypericin in the TME.
• To evaluate hypericin as a photodynamic therapy (PDT) or sonodynamic therapy (SDT)-based ICD inducer.
• To highlight the potential of nanocarrier-formulated hypericin for cancer therapy.

Main Methods:

• Literature review of studies on hypericin, ICD, PDT, SDT, and nanocarrier delivery.
• Synthesis of current knowledge on hypericin's mechanisms in modulating tumor immunity.
• Evaluation of hypericin's role in generating reactive oxygen species (ROS) and inducing endoplasmic reticulum stress-mediated ICD.

Main Results:

• Hypericin, derived from *Hypericum perforatum*, exhibits anticancer properties and modulates tumor immunity.
• Hypericin, via PDT/SDT, induces ICD by generating ROS and ER stress.
• Nanocarrier delivery enhances hypericin's solubility, tumor accumulation, and ROS production.

Conclusions:

• Hypericin shows potential as a natural, safe inducer of ICD to overcome TME-induced immunosuppression.
• Nanocarrier-mediated hypericin delivery can improve therapeutic outcomes in cancer immunotherapy.
• Nanosized hypericin formulations may accelerate the development of novel ICD inducers and immunomodulators.