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 a hypoxic tumor microenvironment (TME) seriously hindered the bioapplications 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 (O-2) into hypoxic TME for enhancing PDT efficiency. The BPQD-hybridized mesoporous silica framework (BMSF) with in situ synthesized Pt nanoparticles (PtNPs) in the BMSF is simply prepared. After being 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 O-2 incubation, the PEG-BMSF@Pt nanocatalyst exhibits 4.2-folds O-2 and 1.6-folds O-1(2) generation ability in a mimetic closed system in the presence of both H2O2 and near-infrared laser. In a mouse model, the Apt-BMSF@Pt can effectively accumulate into tumor sites, and the core of BMSF subsequently can act as a photosensitizer to generate reactive oxygen species, while the PtNPs can serve as a catalyst to convert O-2 into O-2 for enhancing PDT through self-compensation mechanisms in hypoxic TME. By comparison 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.