Abstract
ABSTRACT Multifunctional nanocarriers have attracted considerable interest in improving cancer treatment outcomes. Poly(lactide-co-glycolide) (PLGA) nanospheres encapsulating copper oxide nanoparticles (CuO-NPs) are characterized by antitumor activity and exhibit dual-modal contrast-enhancing capabilities. An in vitro evaluation demonstrates that this delivery system allows controlled and sustained release of CuO-NPs. To achieve localized release on demand, an external stimulation by laser irradiation is suggested. Furthermore, to enable simultaneous complementary photothermal therapy, polydopamine (PDA) coating for augmented laser absorption is proposed. To this aim, two formulations of CuO-NPs loaded nanospheres are prepared from PLGA polymers RG-504 H (H-PLGA) and RG-502 H (L-PLGA) as scaffolds for surface modification through in situ polymerization of dopamine and then PEGylation. The obtained CuO-NPs-based multifunctional nanocarriers are characterized, and photothermal effects are examined as a function of wavelength and time. The results show that 808 nm laser irradiation of the coated nanospheres yields maximal temperature elevation (T = 41°C) and stimulates 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 with L-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 of diagnostic imaging and laser-induced drug release combined with thermal therapy.
Highlights
Nanocarriers have been extensively studied to address aspects of anticancer multifunctional agents [1]
To evaluate the PLGA potential to act as a component of a U photothermal controlled delivery system for CuO-NPs, two different molecular weights N (MW) were selected: Resomer® RG 504H (Mw 38-54 kDa) and RG 502H (MW 7A 17kDa), referred to in this study as high MW PLGA (H-PLGA) and low MW PLGA (LM PLGA), respectively
Apart from the MW, it is of the utmost importance to D keep all other polymer properties and process parameters unchanged
Summary
Due to the monofunctionality of most conventional agents, multi-component nanocarriers face difficulties in passing regulatory and safety requirements To overcome these limitations, significant efforts have been devoted to seeking components possessing inherent multifunctional capabilities. CuO-NPs are among the most widely applied inorganic nano-materials, S with remarkable antimicrobial activity against gram-positive and gram-negative U bacterial strains [5,6,7]. These NPs are a potentially useful agent to inhibit N candidiasis [8] and viral infections [9] in human environments. An in vivo study showed that folate-conjugated CuO-NPs
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