Synergistic application of phototherapy and immunotherapy

The article “Stable triangle: nanomedicine-based synergistic application of phototherapy and immunotherapy for tumor treatment” published by Cai et al. in the Journal of Nanobiotechnology (2024), explores how combining phototherapy and immunotherapy can address the limitations of traditional cancer treatments. These conventional methods, such as surgery, chemotherapy, and radiotherapy, often lead to extensive damage to normal cells, drug resistance, and failure to prevent metastasis. As a result, researchers have turned to novel approaches like phototherapy and immunotherapy, especially when combined with nanomedicine.

The paper highlights that phototherapy includes two primary methods: photodynamic therapy (PDT) and photothermal therapy (PTT). When exposed to light, PDT uses photosensitizers that generate reactive oxygen species (ROS), damaging critical cell structures and inducing cell death. The origins of PDT date back to Dr. Dougherty’s 1970s experiments, where laser irradiation combined with hematoporphyrin derivatives showed efficacy in treating cancers like lung and bladder cancer. However, PDT’s fundamental limitation is poor light penetration into tissues, reducing its effectiveness in deeper tumors. PTT, which uses light energy converted into heat to destroy cancer cells, faces challenges like heat diffusion and tumor resistance.

Nanomedicine plays a pivotal role in enhancing the precision and effectiveness of phototherapy. Due to their small size and large surface area, nanoparticles improve drug delivery and better target tumors. By exploiting the enhanced permeability and retention (EPR) effect, nanoparticles accumulate more efficiently in tumor tissues. This leads to higher concentrations of therapeutic agents at the tumor site while minimizing damage to healthy tissues.

Immunotherapy is also recognized as a very promising cancer treatment, with strategies like immune checkpoint inhibitors, adoptive cell therapy, and cancer vaccines showing potential. However, its limitations include low response rates, immune-related adverse events, and a complex, costly preparation process. To improve treatment outcomes, researchers have explored combining immunotherapy with phototherapy. This combination aims to induce immunogenic cell death (ICD), which triggers a robust anti-tumor immune response. ICD releases tumor antigens and damage-associated molecular patterns (DAMPs), priming the immune system to attack cancer cells and potentially preventing recurrence.

Nanomaterials enhance the synergy between phototherapy and immunotherapy. These materials improve drug delivery and modify the tumor microenvironment, often characterized by hypoxia, which hinders treatment. Strategies such as using nanoenzymes to catalyze the decomposition of hydrogen peroxide to generate oxygen in tumors help alleviate hypoxia, enhancing the efficacy of both therapies.

While the synergistic application of phototherapy and immunotherapy shows promise, several challenges remain. Improving light penetration for deeper tumors and addressing the short lifespan of ROS generated during treatment are among the obstacles to be addressed. Translating these nanomedicine-based therapies into clinical practice requires further research, particularly regarding scalability and potential toxicity in humans.

Combining phototherapy and immunotherapy via nanomaterials represents a novel and promising avenue for cancer treatment. Enhancing the precision, targeting, and immune-stimulating effects of these therapies offers the potential for more durable and effective cancer treatments. Overcoming these therapies' technical and biological challenges will be critical for their successful application in clinical settings.