Supporting data for "Photosensitizer-loaded nanoformulations enhance anti-cancer immune response by combinational oxidation therapy"

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.

本数据集包含提取自本人博士学位论文的原始实验数据，涵盖三项研究课题。原始数据涵盖载光敏剂纳米制剂的表征、体外细胞实验、体内抗肿瘤研究等内容。下文为该论文的摘要，概述了其研究范畴。
肿瘤转移与免疫逃逸是癌症患者治疗失败及预后不良的常见诱因。手术、化疗、放疗等传统疗法在抑制肿瘤转移、激活系统性抗肿瘤免疫应答方面疗效有限。当前免疫治疗手段如免疫检查点阻断疗法与嵌合抗原受体T细胞疗法的疗效，在很大程度上受免疫冷实体瘤微环境的制约。为破解上述难题，载光敏剂纳米制剂作为一种创新策略应运而生，可通过氧化治疗与免疫原性细胞死亡来激活免疫应答。
本论文致力于开发载光敏剂纳米制剂，以实现联合氧化治疗，进而达成高效的癌症免疫治疗。本研究以维替泊芬（Verteporfin）作为光敏剂、β-拉帕醌（β-lapachone）作为化学动力治疗试剂，分别探索了光动力治疗（PDT）与化学动力治疗（CDT）在乳腺或结肠癌细胞中提升氧化应激水平的效果。此外，本研究还探究了将氧化治疗与mTOR抑制、表观遗传调控或铁死亡相结合的潜力，以放大氧化损伤、增强癌细胞凋亡及后续的免疫激活效应。
第一项课题中，本研究开发了一种由维替泊芬与Torin 1组成的无载体纳米药物制剂，用于乳腺癌免疫治疗。维替泊芬作为光敏剂，可在近红外（NIR）光照射下产生活性氧（ROS）；Torin 1作为mTOR抑制剂，能够抑制光动力治疗过程中缺氧诱导的血管生成。这两种药物分子可通过物理相互作用自组装形成纳米颗粒。在4T1荷瘤小鼠模型中，光照条件下，光动力治疗与mTOR抑制产生协同效应，促进乳腺癌细胞凋亡、增强免疫原性细胞死亡，并重塑肿瘤微环境。
第二项课题中，本研究设计了一种由β-拉帕醌、CUDC101与IR783组成的无载体纳米制剂，以增强抗肿瘤免疫应答。β-拉帕醌可通过特异性生化反应在乳腺癌细胞中产生活性氧；CUDC101作为表皮生长因子受体（EGFR）与组蛋白去乙酰化酶（HDAC）双重抑制剂，可调控癌基因的表达。为整合氧化治疗与表观遗传调控，本研究选用常用光敏剂IR783作为稳定剂，与上述两种药物分子共同构建纳米药物。在双侧肿瘤模型中，该纳米药物可通过激活细胞毒性T细胞与效应记忆T细胞应答，抑制原发肿瘤与远端肿瘤的生长。
第三项课题中，本研究探索了一种光敏脂质纳米颗粒（LNP）制剂，用于共递送FSP1小干扰RNA（siRNA）与维替泊芬以开展结肠癌免疫治疗。维替泊芬可与脂质组分自组装形成光敏脂质纳米颗粒，且不会影响小干扰RNA的装载能力。本研究通过调节表面性质对脂质纳米颗粒进行了优化，以提升其在结肠癌细胞中的摄取效率与内体逃逸水平。在近红外光照射下，该光敏脂质纳米颗粒可通过FSP1基因沉默与氧化应激，在结肠肿瘤组织中协同诱导铁死亡，进而引发免疫原性细胞死亡并激活强效的抗肿瘤免疫。
综上，本论文开发了三种创新性的载光敏剂纳米制剂，旨在通过联合氧化治疗增强抗肿瘤免疫应答。本研究为无载体纳米药物与脂质纳米颗粒的研发提供了新的思路，有望推动其在临床中安全有效地用于乳腺或结肠癌的治疗。