Laser-induced thermal response and controlled release of copper oxide nanoparticles from multifunctional polymeric nanocarriers

Multifunctional nanocarriers have attracted considerable interest in improving cancer treat-ment outcomes. Poly(lactide-co-glycolide) (PLGA) nanospheres encapsulating copper oxidenanoparticles (CuO-NPs) are characterized by antitumor activity and exhibit dual-modal con-trast-enhancing capabilities. An in vitro evaluation demonstrates that this delivery systemallows controlled and sustained release of CuO-NPs. To achieve localized release on demand,an external stimulation by laser irradiation is suggested. Furthermore, to enable simultaneouscomplementary photothermal therapy, polydopamine (PDA) coating for augmented laserabsorption is proposed. To this aim, two formulations of CuO-NPs loaded nanospheres areprepared from PLGA polymers RG-504 H (H-PLGA) and RG-502 H (L-PLGA) as scaffolds forsurface modification through in situ polymerization of dopamine and then PEGylation. Theobtained CuO-NPs-based multifunctional nanocarriers are characterized, and photothermaleffects are examined as a function of wavelength and time. The results show that 808 nm laserirradiation of the coated nanospheres yields maximal temperature elevation (T = 41°C) andstimulates copper release at a much faster rate compared to non-irradiated formulations. Laser-triggered CuO-NP release is mainly depended on the PLGA core, resulting in faster release withL-PLGA, which also yielded potent anti-tumor efficacy in head and neck cancer cell line (Cal-33).In conclusion, the suggested multifunctional nanoplatform offers the integrated benefits ofdiagnostic imaging and laser-induced drug release combined with thermal therapy.