FRET-based mesoporous organosilica nanoplatforms for in vitro and in vivo anticancer two-photon photodynamic therapy†

We report the synthesis of multifunctional periodic mesoporous organosilica nanoparticles (PMO NPs) with substantial two-photon absorption properties and targeting capability for two-photon excitation fluorescence (TPEF) and photodynamic therapy (TPE-PDT). Prepared using an adapted sol–gel synthesis, the nanoplatforms integrated two silylated chromophores in their three-dimensional matrix to maximize non-radiative Förster resonance energy transfer from a high two-photon absorption fluorophore donor to a porphyrin derivative acceptor, leading to an enhanced generation of reactive oxygen species. Combinations of biodegradable and non-biodegradable bis(triethoxysilyl)alkoxysilanes were employed for the synthesis of the NPs, and the corresponding photophysical studies revealed high efficiency levels of FRET. Next, the cellular uptake and toxicities of pristine and functionalized NPs were evaluated on breast cancer cell lines upon TPEF and TPE-PDT. Notably, the use of TPE-PDT treatment led to high levels of phototoxicity on MCF-7 and MDA-MB-231 cancer cells with substantial effects when compared to one-photon excitation (OPE)-PDT treatment. Preliminary in vivo data on selective and biodegradable NPs showed a significant phototoxicity towards MDA-MB-231 on zebrafish xenograft embryos, making these advanced nanoplatforms promising candidates for future TPE-PDT-based cancer treatments.