Black phosphorus quantum dots encapsulated in anionic waterborne polyurethane nanoparticles for enhancing stability and reactive oxygen species generation for cancer PDT/PTT therapy

Black phosphorus quantum dots (BPQDs) with excellent biocompatibility, outstanding photothermal and photodynamic efficacies have attracted significant attention in cancer therapy. However, the low environmental stability and poor dispersity of BPQDs limit their practical applications. In the present work, biocompatible anionic waterborne polyurethane (WPU) nanoparticles were synthesized from castor oil to encapsulate the BPQDs. The WPU-BPQDs with a BPQDs loading capacity of about 13.8% (w/w) exhibited significantly improved dispersion and environmental stability without affecting the photothermal efficiency of BPQDs. Intriguingly, it was found that WPU encapsulation led to significant enhancement in the reactive oxygen species (ROS) generation of BPQDs, which indicated the enhanced photodynamic efficacy of the encapsulated BPQDs as compared to the bare BPQDs. The effect of solution pH on the ROS generation efficiency of BPQDs and the pH variation caused by BPQDs degradation was then investigated to explore the possible mechanism. In acidic solution, ROS generation was suppressed, while BPQDs degradation led to the acidification of the solution. Fortunately, after being encapsulated inside the WPU nanoparticles, the degradation rate of BPQDs became slower, while the acidic environment around BPQDs was favorably regulated by WPU nanoparticles having a special electrochemical double layer consisting of interior COO^- and exterior NH(Et₃)⁺, thus endowing the WPU-BPQDs-boosted production of ROS as compared to the bare BPQDs. Considering the undesired acidic tumor environment, this unique pH regulation effect of WPU-BPQDs would be beneficial for in vivo photodynamic efficacy. Both in vitro and in vivo experiments showed that WPU-BPQDs could effectively improve photodynamic therapy (PDT) and maintain outstanding photothermal therapy (PTT) effects. Together with the excellent dispersity, biocompatibility, and easy biodegradability, WPU-BPQDs can be a promising agent for PDT/PTT cancer treatments.