Photocatalysis Enhancement for Programmable Killing of Hepatocellular Carcinoma through Self-Compensation Mechanisms based on Black Phosphorus Quantum Dot hybridized Nanocatalysts.

Recently reported black phosphorus quantum dots (BPQDs) possess unique photocatalysis activities. However, the environmental instability accompanied by hypoxic tumor microenvironment (TME) seriously hindered the bio-applications of BPQDs, especially in oxygen-dependent photodynamic therapy (PDT). Here, we construct a hepatocellular carcinoma (HCC) specific targeting aptamer "TLS11a" decorated BPQDs-hybridized nanocatalyst which can specifically target HCC tumor cells and self-compensate oxygen (O2) into hypoxic TME for enhancing PDT efficiency. The BPQDs-hybridized mesoporous silica framework (BMSF) with in-situ synthesized Pt nanoparticles (PtNPs) in the BMSF is simply prepared. After decorated by TLS11a aptamer / Mal-PEG-NHS, the resultant nanosystem (refer as Apt-BMSF@Pt) exhibits excellent environmental stability, active targeting ability to HCC cells and self-compensation ability of oxygen. Compared with the PEG-BMSF@Pt without H2O2 incubation, the PEG-BMSF@Pt nanocatalyst exhibits 4.2-folds O2 and 1.6-folds 1O2 generation ability in a mimetic closed-system in the presence of both H2O2 and NIR laser. In a mouse model, the Apt-BMSF@Pt can effectively accumulate into tumor sites, and the core of BMSF subsequently can act as photosensitizer to generate ROS, while the PtNPs can serve as a catalyst to convert H2O2 to O2 for enhancing PDT through self-compensation mechanisms in hypoxic TME. By comparation of the tumor volume / weight, H&E and immunohistochemical analysis, the excellent antitumor effects with minimized side effects of our Apt-BMSF@Pt could be demonstrated in vivo. Taken together, the current study suggests that our Apt-BMSF@Pt could act as an active targeting nanocatalyst for programmable killing of cancer cells in hypoxic TME.