NIR-Activated "OFF/ON" Photodynamic Therapy by a Hybrid Nanoplatform with Upper Critical Solution Temperature Block Copolymers and Gold Nanorods.

Photodynamic therapy (PDT) is a promising treatment modality for cancer treatment owing to its minimally invasive nature and negligible drug resistance. However, the disadvantages of conventional photosensitizers including universal aggregation-caused quenching (ACQ) effect or nonselective activation are still major hurdles for PDT clinical application. Herein, a new strategy for flexible manipulating photosensitizers in effective quenching and quick recovery of photoactivation is presented by introducing porphyrin units into upper critical solution temperature (UCST) block copolymer decorated gold nanorods (AuNR-P(AAm-co-AN-co-TPP)-b-PEG). The UCST block copolymer can achieve a self-quenching effect to make the porphyrin photosensitizers in the "Off" state by π-π stacking and hydrogen bonding interactions at physiological temperature, which greatly minimizes the nonselective phototoxicity of the photosensitizers to meet the requirement of phototherapy protected from sunlight. After the immigration of AuNR-P(AAm-co-AN-co-TPP)-b-PEG nanoparticles into the tumor tissue and the internalization by cancer cells, the UCST polymer chains can be extended under the local heating of AuNRs by NIR light irradiation, and then porphyrin photosensitizers are turned "On" to dramatically boost the PDT efficiency. Therefore, the process of PDT could be well manipulated in the "Off/On" state by the hybrid nanoplatform with UCST block copolymers and AuNRs, which will open new horizons for clinical treatments of PDT.