Over the past few decades, considerable attention has been given to improving the photoactivity and biocompatibility of hydrophobic photosensitizing drugs for light-activatable biomedical applications. It is increasingly clear that photosensitizing biomolecules, based on chemical conjugation or association of photosensitizers with biomolecules (e.g., lipids, polymers, antibodies, and Pluronic), strongly influence the performance of a given photosensitizer in biological environments. However, the numerous studies that have revealed PSBMs are not readily comparable as they cover a wide range of macromolecules, evaluated across a range of experimental conditions. Here, we prepared and characterized a series of well-defined PSBMs and pure drug crystal based on a clinically used photosensitizer—benzoporphyrin derivative (BPD). Our results illuminate the variable trafficking and end effects of clinically relevant PSBMs and BPD nanocrystals, providing valuable insights into methods of PSMB evaluation as well as strategies to select PSMBs based on subcellular targets and cytotoxic mechanisms. More importantly, these results demonstrate that biologically-informed combinations of PSBMs and carrier-free photosensitizers to target multiple subcellular organelles may lead to enhanced therapeutic effects in gliomas.
Over the past few decades, considerable attention has been given to improving the photoactivity and biocompatibility of hydrophobic photosensitizing drugs for light-activatable biomedical applications. It is increasingly clear that photosensitizing biomolecules, based on chemical conjugation or association of photosensitizers with biomolecules (e.g., lipids, polymers, antibodies, and Pluronic), strongly influence the performance of a given photosensitizer in biological environments. However, the numerous studies that have revealed PSBMs are not readily comparable as they cover a wide range of macromolecules, evaluated across a range of experimental conditions. Here, we prepared and characterized a series of well-defined PSBMs and pure drug crystal based on a clinically used photosensitizer—benzoporphyrin derivative (BPD). Our results illuminate the variable trafficking and end effects of clinically relevant PSBMs and BPD nanocrystals, providing valuable insights into methods of PSMB evaluation as well as strategies to select PSMBs based on subcellular targets and cytotoxic mechanisms. More importantly, these results demonstrate that biologically-informed combinations of PSBMs and carrier-free photosensitizers to target multiple subcellular organelles may lead to enhanced therapeutic effects in gliomas.
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