DOI: 10.25442/hku.29183186
title: Supporting data for "Photosensitizer-loaded nanoformulations enhance anti-cancer immune response by combinational oxidation therapy"

description: This dataset contains original data extracted from my PhD thesis, which involves three projects. The original data include the characterization of photosensitizer-loaded nanoformulations, in vitro cell experiments, in vivo anti-cancer studies, and so on. Below is the abstract of the thesis outlining its contents.Metastasis and immune evasion are common causes of treatment failure and poor prognosis in cancer patients. Traditional therapies such as surgery, chemotherapy, and radiotherapy have limited therapeutic effects in inhibiting metastasis and activating systemic anti-tumor immune response. The efficacy of current immunotherapy such as immune checkpoint blockade and chimeric antigen receptor T cell is considerably hindered by immunologically cold solid tumor microenvironment. To overcome these challenges, photosensitizer-loaded nanoparticle formulations have emerged as an innovative approach to stimulate immune response through oxidation therapy and immunogenic cell death.<br>This thesis is dedicated to developing photosensitizer-loaded nanoformulations to achieve combinational oxidation therapy for efficient cancer immunotherapy. Both photodynamic therapy (PDT) and chemodynamic therapy (CDT) are explored to elevate oxidative stress in breast or colon cancer cells with the help of Verteporfin as the photosensitizer and β-lapachone as the CDT agent. This work also investigates the potential of combining oxidation therapy with mTOR inhibition, epigenetic modulation, or ferroptosis to amplify oxidative damage and enhance cancer cell apoptosis and subsequent immune activation.<br>In the first project, a carrier-free nanodrug formulation composed of Verteporfin and Torin 1 is developed for breast cancer immunotherapy. Verteporfin serves as the photosensitizer to generate reactive oxygen species (ROS) upon near-infrared (NIR) light irradiation. Torin 1 is a mTOR inhibitor and can suppress hypoxia-elicited angiogenesis during PDT. These two drug molecules can self-assemble to form nanoparticles through physical interactions. Under light irradiation, PDT synergizes with mTOR inhibition to promote breast cancer apoptosis, boost immunogenic cell death, and remodel tumor microenvironment in the 4T1 tumor-bearing mouse model.<br>In the second project, a carrier-free nanoformulation consisting of β-lapachone, CUDC101, and IR783 is designed to enhance anti-cancer immune response. β-lapachone can generate ROS in breast cancer cells through specific biochemical reactions, while CUDC101 is an EGFR and HDAC dual inhibitor that regulates the expression of oncogenes. To integrate oxidation therapy and epigenetic modulation, IR783, a commonly used photosensitizer, is utilized as a stabilizer to form nanodrugs with these two drug molecules. In the bilateral tumor model, the nanodrugs can suppress the growth of primary and distant tumors by activating cytotoxic T cell and effector memory T cell response.<br>In the third project, a photosensitive lipid nanoparticle (LNP) formulation is explored to co-deliver FSP1 siRNA and Verteporfin for colon cancer immunotherapy. Verteporfin can self-assemble with lipid components to form photosensitive LNPs without affecting siRNA loading ability. The LNPs are further optimized by tuning the surface properties to enhance the cellular uptake and endosomal escape levels in colon cancer cells. Under NIR light exposure, the photosensitive LNPs synergistically promote ferroptosis in colon tumor tissues via FSP1 gene silencing and oxidative stress, leading to immunogenic cell death and robust anti-cancer immunity.<br>In summary, this thesis presents three innovative photosensitizer-loaded nanoformulations aimed at boosting the anti-cancer immune response through combinational oxidation therapy. This study provides novel perspectives on the advancement of carrier-free nanodrugs and LNPs for safe and effective treatment of breast or colon cancer in clinical settings.