Scientists are making significant strides in cancer treatment with an innovative approach known as photoimmunotherapy. This technique merges phototherapy and immunotherapy to precisely target and destroy cancer cells, offering new hope for more effective and less invasive treatments.
Illustration of multifunctional nanoplatforms M@P inducing cancer cells pyroptosis and ferroptosis for cancer photoimmunotherapy. Nanoplatforms M@P is constructed by self-assembly of photosensitizer MTCN-3 and immunoadjuvant Poly(I: C), which are further encapsulated in amphiphilic polymers. This resulting nanoplatform has the characteristics of cancer cell targeting and pH response. After targeting lysosomes, M@P can cause lysosome dysfunction through the generation of reactive oxygen species and heat under light irradiation, triggering pyroptosis and ferroptosis of tumor cells, achieving immunogenic cell death, and further enhancing immunotherapy through the combined effect with the immunoadjuvant Poly(I: C). Image Credit: Zhichao Wang, Yuqi Tang, and Quan Li.
Photoimmunotherapy works by introducing a photosensitizer or nanomaterial into tumor tissue. When exposed to specific wavelengths of light, it activates a localized therapeutic response. This can include photothermal or photodynamic effects, which either directly eliminate cancer cells or trigger immunogenic cell death—a process that prompts the immune system to attack the tumor.
During immunogenic cell death, cancer cells release signaling molecules known as damage-associated molecular patterns (DAMPs). These molecules act as natural immune adjuvants, binding to pattern recognition receptors on dendritic cells, promoting their maturation, and initiating a series of cellular responses that activate both innate and adaptive immune responses.
Two well-studied forms of immunogenic cell death, pyroptosis and ferroptosis, have been shown to play a key role in modulating the immune system. Traditionally, therapies inducing pyroptosis and ferroptosis have relied on chemotherapeutic drugs, but their nonspecific targeting and severe side effects have limited their effectiveness.
In a recent study published in Light: Science & Applications, a research team led by Professor Quan Li from the Institute of Advanced Materials and the School of Chemistry and Chemical Engineering at Southeast University, China, along with collaborators from the Materials Science Graduate Program at Kent State University, US, developed a lysosome-targeted nanoplatform designed to enhance cancer photoimmunotherapy.
The nanoplatform, called M@P, was created through the self-assembly of the photosensitizer MTCN-3 and the immunoadjuvant Poly(I: C), which was then encapsulated in amphiphilic polymers.
This nanoplatform is engineered to actively target tumors and accumulate in the lysosomes of cancer cells. Upon light irradiation, it generates a significant amount of reactive oxygen species and heat, inducing lysosomal dysfunction and triggering pyroptosis and ferroptosis. This process leads to immunogenic cell death and enhances the effectiveness of immunotherapy when combined with Poly(I: C).
The study demonstrated the therapeutic potential of M@P in a tumor-bearing mouse model with poor immunogenicity. Results showed that M@P promoted the production of tumor-specific antigens and facilitated dendritic cell maturation, which in turn stimulated the proliferation of activated T cells. By the ninth day of treatment, both primary and distant tumor growth in mice was significantly inhibited.
This research introduces a novel strategy for designing dual-function pyroptosis and ferroptosis inducers, paving the way for further advancements in cancer photoimmunotherapy.
Journal Reference:
Wang, Z., et al. (2025) A self-assembling nanoplatform for pyroptosis and ferroptosis enhanced cancer photoimmunotherapy. Light: Science & Applications. doi.org/10.1038/s41377-024-01673-1