Development of a novel anti-tumor theranostic platform: a near-infrared molecular upconversion sensitizer for deep-seated cancer photodynamic therapy

Upconversion-based photon-initiated therapeutic modalities, photodynamic therapy (PDT) in particular, have shown significant clinical potential in deep-seated tumor treatment. However, traditional multiphoton upconversion materials involving lanthanide (ion)-doped upconversion nanoparticles (UCNPs) and two-photon absorption (TPA) dyes often suffer from lots of inherent problems such as unknown systematic toxicity, low reproducibility, and extremely high irradiation intensity for realization of multiphoton upconversion excitation. Herein, for the first time, we report a one-photon excitation molecular photosensitizer (FUCP-1) based on a frequency upconversion luminescence (FUCL) mechanism. Under anti-Stokes (808 nm) excitation, FUCP-1 showed excellent photostability and outstanding upconversion luminescence quantum yield (up to 12.6%) for imaging-guided PDT. In vitro cellular toxicity evaluation presented outstanding inhibition of 4T1 cells by FUCP-1 with 808 nm laser irradiation (the half maximal inhibitory concentration was as low as 2.06 μM). After intravenous injection, FUCP-1 could specifically accumulate at tumor sites and obviously suppress the growth of deep-seated tumors during PDT. More importantly, FUCP-1 could be fully metabolized from the body within 24 h, thus dramatically minimizing systemic toxicity. This study might pave a new way for upconversion-based deep-seated cancer PDT.