Photodynamic therapy (PDT) is a promising modality for cancer treatment. The essential element in PDT is the photosensitizer, which can be excited by light of a specific wavelength to generate cytotoxic oxygen species (ROS) capable of killing tumor cells. The effectiveness of PDT is limited in part by the low yield of ROS from existing photosensitizers and the unwanted side effects induced by the photosensitizers toward normal cells. Thus the design of nanoplatforms with enhanced PDT is highly desirable but remains challenging. Here, we developed a heavy atom (I) containing dipyrromethene boron difluoride (BODIPY) dye with a silylated functional group, which can be covalently incorporated into a silica matrix to form dye-doped nanoparticles. The incorporated heavy atoms can enhance the generation efficiency of ROS. Meanwhile, the covalently dye-encapsulated nanoparticles can significantly reduce dye leakage and subsequently reduce unwanted side effects. The nanoparticles were successfully taken up by various tumor cells and showed salient phototoxicity against these cells upon light irradiation, demonstrating promising applications in PDT. Moreover, the incorporated iodine atom can be replaced by a radiolabeled iodine atom (e.g., I-124, I-125). The resulting nanoparticles will be good contrast agents for positron emission tomography (PET) imaging with their PDT functionality retained.
Two silylated BODIPY derivatives were synthesized, characterized and used for the fabrication of the dye-encapsulated silica nanoparticles. The fluorophores were covalently incorporated into the silica matrix to minimize any fluorophore leakage. The synthesized fluorophore-doped nanoparticles were stable in aqueous solution and monodisperse with diameters of 20-25 nm. By incorporating the two BODIPY dyes simultaneously at a controlled ratio, silica nanoparticles with switchable emitting wavelengths were achieved with a change in the excitation wavelength. Thus by using the dual-fluorophore-doped nanoparticles, two-color imaging was demonstrated with minimal background signal by employing an appropriate excitation light source and appropriate excitation/emission filter sets. Further, the surfaces of the dual-fluorophore-doped nanoparticles were functionalized with folic acid to allow for the recognition of HeLa cells which over-express the folate receptors.
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