In Vitro and In Vivo Photothermal and Photoacoustic Activities of Polymeric Nanoparticles Loaded with Nickel, Palladium, and Platinum-Bis(dithiolene) Complexes

Jean Baptiste, Pluta, Lamiaa M.A., Ali, Romain, Guechaichia, Victorien, Massé, Thiviya, Parthipan, Nathalie, Bellec, Sandrine, Cammas-Marion, Francois, Varray, Christophe, Nguyen, Magali, Gary-Bobo, Franck, Camerel

ChemMedChem |

The development of nanosystems with enhanced photothermal and photoacoustic properties is crucial for advancing theranostic applications in cancer therapy. This study explores polymeric nanoparticles (NPs) constituted by a biocompatible poly(ethylene glycol)-block-poly(benzyl malate) copolymer and loaded with metal-bis(dithiolene) complexes (M = Ni, Pd, Pt). These NPs, prepared via a robust nanoprecipitation method, demonstrate uniform morphology, efficient encapsulation (≈70%), and tailored near-infrared (NIR) optical absorption properties. Photothermal and photoacoustic evaluations reveal superior performance of palladium-loaded NPs, offering high contrast for imaging and significant temperature increases under NIR laser irradiation. Cytotoxicity assays confirm their nontoxicity without laser exposure, while effective cancer cell eradication is achieved upon irradiation at power densities ≥2 W cm−2. In vivo experiments on zebrafish embryos bearing human cancer xenografts show significant tumor size reduction (20%) post–treatment with palladium-loaded NPs under 880 nm laser irradiation. These findings underscore that metal-bis(dithiolene)-loaded NPs can be versatile agents for combined diagnostics and photothermal therapy, paving the way for further optimization and clinical translation.