Smart Ultrasound-Triggered Doxorubicin-Loaded Nanoliposomes With Improved Therapeutic Response: A Comparative Study

Doxorubicin (DOX) effectiveness in cancer treatment is hampered by its nonspecific accumulation in organs. Ultrasound (US) is a promising noninvasive targeting approach. Currently, studies focus on developing more DOX-loaded US-triggered formulations with different composition, DOX doses, and US intensities. No studies were emerged to compare and select the most effective approach to endure. The aim of this study is to prepare and comparatively address the therapeutic potential of 2 different US-tunable nanosized liposomes while minimizing DOX dose and US intensity. One of the liposomes is tailored to be responsive for US non-thermal effects (DOX-USLs) and the other is designed to be thermoresponsive (DOX-TSLs). Both systems were compared in terms of cellular uptake, cell viability and apoptosis using HeLa cells as a cancer model. The IC₅₀ of DOX-USLs and DOX-TSLs was 2.5-5 times lower than that of free DOX. IC₅₀ reflected the significant superior cytotoxicity of DOX-TSLs (0.1 μg/mL) over DOX-USLs (0.2 μg/mL). Cellular uptake indicated that DOX-TSLs were inside the nucleus while DOX-USLs were accumulated everywhere in the intracellular space with lower fluorescent intensity inside the nucleus. However, both showed enhanced apoptosis in terms of enhanced caspase-3 activity, reduced glutathione levels and DNA fragmentation when compared to free DOX treatment.