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.

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Objectives-Brain treatments using focused ultrasound (FUS) offer a new range of noninvasive transcranial therapies. The acoustic energy deposition during these procedures may induce a temperature elevation in the tissue; therefore, noninvasive thermal monitoring is essential. Magnetic resonance imaging is the current adopted monitoring modality, but its high operational costs and limited availability may hinder the accessibility to FUS treatments. Aiming at the development of a thermometric ultrasound (US) method for the brain, the specific objective of this investigation was to study the acoustic thermal response of the speed of sound (SOS) and attenuation coefficient (AC) of different brain tissues: namely white matter (WM) and cortical matter.Methods-Sixteen ex vivo bovine brain samples were investigated. These included 7 WM and 9 cortical matter samples. The samples were gradually heated to about 45 C and then repeatedly scanned while cooling using a computerized US system in the through-transmission mode. The temperature was simultaneously registered with thermocouples. From the scans, the normalized SOS and AC for both tissues were calculated.Results-The results demonstrated a characteristic cooldown temporal behavior for the normalized AC and SOS curves, which were related to the temperature. The SOS curves enabled clear differentiation between the tissue types but depicted more scattered trajectories for the WM tissue. As for the AC curves, the WM depicted a linear behavior in relation to the temperature. However, both tissue types had rather similar temperature patterns.Conclusions-These findings may contribute to the development of a US temperature-monitoring method during FUS procedures.

Glioblastoma (GBM) is a universally lethal form of brain cancer. The success of novel treatments is hindered by the blood–brain barrier (BBB), which prevents most drugs from penetrating GBM tumors. Sorafenib (SFB), a proapoptotic multikinase inhibitor, has been investigated for the treatment of GBM; however, survival benefit among patients has not improved. Recently, an indocyanine‐stabilized nanoparticulate form of SFB (SFB NPs) with improved tumor accumulation was developed in comparison to SFB alone. Herein, the benefit of SFB NPs and focused ultrasound (FUS)‐mediated BBB disruption is assessed to enable noninvasive, safe, and reversible BBB permeation for enhanced SFB NPs brain accumulation. Treatment of SFB NPs and FUS yields lower IC50 values (2.7 and 29 μm in 2D and 3D U87 cell models vs 7.5 and 37.1 μm for SFB NPs alone). SFB NPs and FUS with microbubbles improve SFB NPs uptake by U87 cells compared to SFB NPs alone (46% increase; p = 0.0123). In vivo, FUS enhances SFB NPs brain accumulation by 2.5‐fold compared to the contralateral hemisphere, and 3.6‐fold compared to unsonicated brains. In conclusion, SFB NPs are a promising agent for GBM treatment and its therapeutic capacity can be potentially enhanced when combined with FUS‐mediated BBB disruption.