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Nanoparticles have become popular photosensitizers for photothermal therapy (PTT), as they can be targeted to specific cancer tissues and deliver a chemotherapeutic drug, providing a multimodal therapeutic approach. Photothermal conversion efficiency of nanoparticles is critical in the assessment of their therapeutic use in PTT. We describe an accurate calorimetric method for the determination of the photothermal conversion efficiency of nanoparticles in solution. A tightly focused laser beam was used to irradiate a cuvette containing a solution of silver sulfide-glutathione quantum dots (Ag2S-GSH QDs), and the maximum steady-state temperature rise was measured with an infrared camera. The data were analyzed using two different photothermal conversion efficiencies, the intrinsic and external conversion efficiencies, to relate the induced heating power of the nanoparticles to the absorbed and incident optical powers, respectively. Measurements with a tunable Ti3+:sapphire laser showed that the intrinsic photothermal conversion efficiency of Ag2S-GSH QDs exceeded 91% over the 720–810 nm wavelength range. The method was also used to analyze poly­(acrylic acid)-coated superparamagnetic iron oxide nanoparticles (PAA/SPIONs), and the intrinsic photothermal conversion efficiency was determined to be 83.4% at 810 nm. This approach is useful for the evaluation of various potential nanoparticles for photothermal therapy applications.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) based on temperature increase and the formation of reactive oxygen species (ROS), respectively, is an exciting avenue to provide local and improved therapy of tumors with minimal off-site toxicity. 5-Aminolevulinic acid (ALA) is one of the most popular PDT pro-drugs, and its efficiency improves significantly when delivered to tumors with nanoparticles (NPs). But the tumor site’s hypoxic environment is a handicap for the oxygen-consuming PDT process. In this work, highly stable, small, theranostic NPs composed of Ag2S quantum dots and MnO2, electrostatically loaded with ALA, were developed for enhanced PDT/PTT combination of tumors. MnO2 catalyzes endogenous H2O2 to O2 conversion and glutathione depletion, enhancing ROS generation and ALA-PDT efficiency. Ag2S quantum dots (AS QDs) conjugated with bovine serum albumin (BSA) support MnO2 formation and stabilization around Ag2S. AS-BSA-MnO2 provided a strong intracellular near-infrared (NIR) signal and increased the solution temperature by 15 °C upon laser irradiation at 808 nm (215 mW, 10 mg/mL), proving the hybrid NP as an optically trackable, long-wavelength PTT agent. In the in vitro studies, no significant cytotoxicity was observed in the absence of laser irradiation in healthy (C2C12) or breast cancer cell lines (SKBR3 and MDA-MB-231). The most effective phototoxicity was observed when AS-BSA-MnO2-ALA-treated cells were co-irradiated for 5 min with 640 nm (300 mW) and 808 nm (700 mW) due to enhanced ALA-PDT combined with PTT. The viability of cancer cells decreased to approximately 5–10% at 50 μg/mL [Ag], corresponding to 1.6 mM [ALA], whereas at the same concentration, individual PTT and PDT treatments decreased the viability to 55–35%, respectively. The late apoptotic death of the treated cells was mostly correlated with high ROS levels and lactate dehydrogenase. Overall, these hybrid NPs overcome tumor hypoxia, deliver ALA to tumor cells, and provide both NIR tracking and enhanced PDT + PTT combination therapy upon short, low-dose co-irradiation at long wavelengths. These agents that may be utilized for treating other cancer types are also highly suitable for in vivo investigations.