A feasible and sensitive colorimetric platform was established for the assay of acetylcholinesterase (AChE) activity and evaluation of its inhibitor screening, based upon the light-accelerating oxidase-mimicking activity of black phosphorus quantum dots (BP QDs). The BP QDs were synthesized through a thermal exfoliation method and characterized using various techniques. The BP QDs exhibit oxidase-mimicking catalytic activity on dissolved oxygen-mediating oxidation of 3,3′,5,5′-tetramethylbenzidine, a typical substrate of oxidase. This results in a transformation of 3,3′,5,5′-tetramethylbenzidine into its blue oxidized product, which has a visible absorption peak at 652 nm. The exposure of 365 nm light irradiation significantly accelerates the oxidase-mimicking activity of the BP QDs and speeds up the reaction efficiency. AChE can specifically catalyze the decomposition of its substrate acetylthiocholine chloride to thiocholine. Thiocholine has reducing capacity and can thus reduce the oxidase-mimicking activity of the BP QDs. As a result, the oxidation of 3,3′,5,5′-tetramethylbenzidine is hindered and the blue solution becomes paler. This gives a linear response for AChE ranging from 0.5 to 10.0 mU mL−1 and a detection limit of 0.17 mU mL−1. The assay was successfully applied to evaluate inhibitor screening with neostigmine as the model.
Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy.
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