(562f) Radioluminescent Nanoparticles for Radiation-Induced Photodynamic Therapy in Cancer

Photodynamic therapy (PDT) is a promising cancer treatment modality involving photosensitizer activation by light to produce cytotoxic species like reactive oxygen species (ROS) or singlet oxygens (¹O₂)¹. While 5-aminolevulinic acid (ALA) PDT is effective for superficial lesions^2,3, its use is limited in deep-seated tumors due to light penetration constraints^4,5. To address this, we developed PEG-PLA-coated CaWO4 nanoparticles (PEG-PLA/CWO NPs) as energy transducers for X-ray radiation-induced PDT (RT-PDT)⁶. These NPs generate ROS upon X-ray exposure and emit blue radioluminescence⁷, activating ALA-derived protoporphyrin IX (PPIX) to induce ¹O₂ production, mimicking ALA-PDT effects⁸. In vivo evaluation using PEG-PLA/CWO NPs and ALA prodrugs in a mouse tumor model demonstrated their efficacy in deep-seated tumors. However, nanoparticle distribution in tumors is limited by the extracellular matrix (ECM)^9,10, prompting the development of collagenase-functionalized PEG-PLA-coated CWO nanoparticles (Col-PEG-PLA/CWO NPs). Collagenase facilitates NP penetration through the ECM, significantly improving their spreading within tumors¹¹. Micro CT analysis revealed a sevenfold enhancement in NP distribution volume with collagenase functionalization. Evaluation of RT-PDT efficacy using Col-PEG-PLA/CWO NPs and ALA prodrugs in the mouse tumor model demonstrated superior tumor growth suppression compared to unfunctionalized NPs. These findings highlight the potential of collagenase-functionalized NPs to improve PDT outcomes in deep-seated tumors.

References

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