Hypoxia caused by photodynamic therapy (PDT) is a major hurdle to cancer treatment since it can promote recurrence and progression by activating angiogenic factors, lowering therapeutic efficacy dramatically. In this work, AZB-I-CAIX2 was developed as a carbonic anhydrase IX (CAIX)-targeting NIR photosensitizer that can overcome the challenge by utilizing a combination of CAIX knockdown and PDT. AZB-I-CAIX2 showed a specific affinity to CAIX-expressed cancer cells and enhanced photocytotoxicity compared to AZB-I-control (the molecule without acetazolamide). Moreover, selective detection and effective cell cytotoxicity of AZB-I-CAIX2 by PDT in hypoxic CAIX-expressed murine cancer cells were achieved. Essentially, AZB-I-CAIX2 could minimize tumor size in the tumor-bearing mice compared to that in the control groups. The results suggested that AZB-I-CAIX2 can improve therapeutic efficiency by preventing PDT-induced hypoxia through CAIX inhibition.
In this work, we synthesize a quinoline-based heptamethine cyanine, QuCy7, with sulfonate groups to enhance water solubility. This dye demonstrates exceptional near-infrared absorption beyond 750 nm, accompanied by photothermal properties but low photostability. Encapsulating QyCy7 with polyethylene glycol to form nanopolymer, QuCy7@mPEG NPs, addresses the issue of its photoinstability. TEM showed that QuCy7@mPEG NPs possess a spherical morphology, featuring a core-shell structure with a size of around 120 nm in diameter. Upon irradiation with an 808 nm laser for 10 min, a significant increase in temperature up to 24 °C can be achieved with a photothermal conversion (PTC) rate of approximately 35%. QuCy7@mPEG NPs exhibit remarkable photothermal stability as compared to QuCy7. The efficiency of QuCy7@mPEG NPs was demonstrated by the in vitro PTT studies. Finally, the nanoparticles' acute toxicity and effectiveness were assessed using the chick embryo model. The results provide compelling evidence that QuCy7@mPEG NPs are safe without inducing hemolysis, inhibit angiogenesis when exposed to light, and exhibit anti-tumor activity with a 76% reduction in tumor size compared to QuCy7 (40%). Thus suggesting the sulfonate groups can enhance water solubility, and its nanopolymer is biocompatible and possesses superior anti-tumor efficacy.