Photodynamic therapy (PDT) is an emerging cancer treatment modality. Despite the focal treatment nature, it is desired that photosensitizers are delivered to tumors with high efficiency and selectivity in a PDT process. Uur recent work on using ferritin, a protein cage (~12 nm), as a photosensitizer carrier. Ferritin can encapsulate photosensitizers such as zinc hexadecafluorophthalocyanine (ZnF<sub>16</sub>Pc) at high efficiency (40 wt%) and they can be modified by both chemical and genetic methods. We have successfully introduced folic acid, RGD4C, and a FAP targeting scFv, onto the surface of ferritins. We then exploited the resulting ferritin cages to navigate PDT to different components in tumors, including cancer cells, cancer endothelial cells, and cancer associated fibroblasts (CAFs). We found that endothelium targeting PDT can enhance the tumor EPR effect to allow for more efficient nanoparticle delivery to tumors. Meanwhile, eliminating CAFs in tumors can improve CD8+ T cell penetration and thereby augmenting anti-tumor immune response. In the second half of the lecture, I will be talking about X-ray induced PDT, or X-PDT, a new technology that is developed to address the shallow penetration issue of conventional PDT. The key component of the X-PDT technology is an integrated nanosystem called X-ray nanosensitizer, which consists of: 1) a nanoparticle scintillator that converts X-ray photos to visible photons and; 2) photosensitizer whose excitation matches the emission of the scintillator. Upon X-ray irradiation, the nanoscintillator works as a transducer, producing X-ray excited optical luminescence; the visible photons, in turn, activate the photosensitizers, producing reactive oxygen species, most importantly singlet oxygen. We have shown that X-PDT can be activated from beneath thick tissues to efficiently kill cancer cells. We also found that X-PDT is more than a simple derivative of PDT; rather, it is a unique combination of PDT and radiation therapy. The two modalities target different cellular components, and the damage overwhelms cellular repairs, leading to synergistic therapy outcomes.

Surface modified nanoparticles for photoimmunotherapy and X-ray induced photodynamic therapy

256th National Meeting (2018)

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