Research Projects

The proposed research aims to develop multimodal nanoparticles to address the challenges of cancer treatment by modulating the tumor microenvironment (TME) and activating non-apoptotic programmed cell death (PCD) pathways, such as ferroptosis and cuproptosis. The multifactorial nature of cancers and their resistance to conventional therapies highlight the need for combination strategies to overcome treatment limitations. This approach seeks to improve therapy, particularly for advanced, metastatic, and therapy-resistant cancers, which are major global health burdens. The TME, characterized by hypoxia, acidosis, oxidative stress, and an immunosuppressive environment, drives cancer progression and resistance to treatment. Conventional therapies, including chemotherapy, radiotherapy, and photodynamic therapy (PDT), often fail due to the TME’s intricate dynamics. For instance, hypoxia undermines the efficacy of PDT, chemotherapy, and sonodynamic therapy (SDT). Moreover, advanced-stage cancers and tumors with mutations, such as RAS, evade apoptosis-based therapies, compounding the therapeutic challenges. Targeting non-apoptotic PCD pathways while simultaneously modulating the TME offers a transformative solution to these limitations. Recent advancements in enzyme-mimetic nanoparticles (nanozymes), particularly catalase-mimetic nanozymes, offer a promising approach to modulate the TME. These nanozymes neutralize hydrogen peroxide, reducing acidosis and alleviate hypoxia by releasing oxygen. However, their clinical utility remains restricted by low catalytic efficiency, poor targeting, and potential long-term toxicity. Alternatively, a plethora of ferroptosis-inducing nanomaterials, primarily iron-based nanoparticles, have been developed in recent years. However, their clinical use is limited by the risks associated with excessive iron accumulation in healthy tissues. This underscores the need for safer ferroptosis strategies. Additionally, cuproptosis and other PCD pathways, such as pyroptosis, remain underexplored but hold significant therapeutic potential. Combining these diverse PCD mechanisms with TME modulation provides a novel strategy to overcome the limitations of current treatments. This project aims to develop multifunctional nanoparticles that modulate the TME by altering hypoxia, acidity, and ROS levels while inducing ferroptosis, cuproptosis, and pyroptosis. This approach is expected to enhance immune responses, improve therapeutic efficacy, and address challenges posed by traditional treatments. By combining these actions, we offer a transformative solution for personalized oncology, with potential for clinical application in advanced, therapy-resistant cancers. Furthermore, we aim to induce PCDs with strategies that minimize long-term toxicity linked to iron and copper-based nanoparticles. The combined modulation of the TME and PCD pathways using nanoparticles is anticipated to be a powerful tool for controlling cancer progression.