Polymer-Upconverting Nanoparticle Hybrid Micelles for Enhanced Synergistic Chemo-Photodynamic Therapy: Effects of Emission-Absorption Spectral Match.

Chemo-photodynamic combined therapy is promising in cancer treatment, although low tissue penetration of visible light for activating photosensitizers (e.g., chlorin e6, Ce6) limited its broad applications. Combination of upcoverting nanoparticles (UCNPs) with the photosensitizers endows us with the possibility to utilize highly tissue penetrable near-infrared light; nevertheless, the mismatch between absorption of common photosensitizers (λabs, mainly red) and emission of UCNPs (λem, mainly green) resulted in low energy utilization and unsatisfied therapeutic efficacy in the current UCNP-PDT (photodymanic therapy) platforms. To resolve this problem, herein, we construct polymer-UCNP hybrid micelles (PUHMs) for codelivery of doxorubicin (DOX) and Ce6, and systemically studied the effects of spectral match between λem of UCNPs and λabs of Ce6 on efficiency of synergistic chemo-photodynamic therapy. Compared with spectrally mismatched PUHMs, the spectrally matched PUHMs can significantly enhance the utilization efficiency of upconverted emission energy to activate the photosensitizers and generate more reactive oxygen species (ROS) for enhanced photodynamic therapy. Meanwhile, as the assembled structure of PUHMs can be destroyed by the oxidation of ROS upon 980 nm laser irradiation because of the hydrophobic-hydrophilic transformation of poly(propylene sulfide) (PPS) segment, the spectrally matched PUHMs triggered faster release of DOX, thus resulting in more effective chemotherapy. As a result, the spectrally matched PUHMs induced more prominent cytotoxicity and superior synergistic therapeutic effect for cancer cells in vitro. Our results demonstrated that such spectrally matched PUHMs provide us with an effective strategy for photodynamic-chemo synergistic therapy.