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Image-Guided Enhanced PDT/PTT Combination Therapy Using Brominated Hemicyanine-Loaded Folate Receptor-Targeting Ag(2)S Quantum Dots

[Image: see text] Tumor-targeting nanoparticles and phototherapies are the two major trends in tumor-specific, local cancer therapy with minimal side effects. Organic photosensitizers (PSs) usually offer effective photodynamic therapy (PDT) but require enhanced solubility and tumor-targeting, which...

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Detalles Bibliográficos
Autores principales: Celikbas, Eda, Saymaz, Ayca, Gunduz, Hande, Koc, Irem, Cakir, Ece, Sennaroglu, Alphan, Kolemen, Safacan, Yagci Acar, Havva, Onbasli, Kubra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197082/
https://www.ncbi.nlm.nih.gov/pubmed/37078275
http://dx.doi.org/10.1021/acs.bioconjchem.3c00096
Descripción
Sumario:[Image: see text] Tumor-targeting nanoparticles and phototherapies are the two major trends in tumor-specific, local cancer therapy with minimal side effects. Organic photosensitizers (PSs) usually offer effective photodynamic therapy (PDT) but require enhanced solubility and tumor-targeting, which may be provided by a nanoparticle. Near-infrared (NIR)-emitting Ag(2)S quantum dots may act as a delivery vehicle for the PS, NIR tracking agent, and as a phototherapy (PTT) agent. A combination of the two provides luminescent dual-phototherapy agents with tumor-specificity and image-guided and enhanced cytotoxicity as a result of synergistic PDT and PTT. In this study, brominated hemicyanine (Hemi-Br), a photosensitizer, was loaded onto folic acid (FA)-tagged, glutathione (GSH)-coated Ag(2)S quantum dots (AS-GSH QDs) to provide enhanced phototoxicity via a photodynamic and mild photothermal effect in folate receptor(+) cancer cell lines at clinically relevant 640 nm irradiation. Final particles (AS-GSH-FA/Hemi-Br) had a hydrodynamic size of 75.5 nm, dual emission at both 705 and 910 nm, and a 93% light-to-heat conversion efficiency under 640 nm laser irradiation. In vitro cytotoxicity studies were conducted with folate receptor (FR)-positive HeLa and -negative A549 cell lines to differentiate receptor-mediated uptake. Enhanced phototoxicity on HeLa cells was observed with AS-GSH-FA/Hemi-Br compared to free Hemi-Br and AS-GSH-FA QDs due to increased uptake of the photosensitizer via active targeting and combination therapy, which is especially visible at the safe dose of single agents. Upon irradiation with a 640 nm (300 mW, 0.78 W/cm(2)) laser for 5 min, the viability of the HeLa cells decreased from 64% to 42 and 25% when treated with free Hemi-Br, AS-GSH-FA, and AS-GSH-FA/Hemi-Br, respectively. Overall, AS-GSH-FA/Hemi-Br provides image-guided enhanced PDT/PTT, which may be adopted for different FR(+) tumors.