Abstract
Cancer is a major health concern and the prognosis is often poor. Significant advances in nanotechnology are now driving a revolution in cancer detection and treatment. The goal of this study was to develop a novel hybrid nanosystem for melanoma treatment, integrating therapeutic and magnetic targeting modalities. Hence, we designed long circulating and pH-sensitive liposomes loading both dichloro(1,10-phenanthroline) copper (II) (Cuphen), a cytotoxic metallodrug, and iron oxide nanoparticles (IONPs). The synthetized IONPs were characterized by transmission electron microscopy and dynamic light scattering. Lipid-based nanoformulations were prepared by the dehydration rehydration method, followed by an extrusion step for reducing and homogenizing the mean size. Liposomes were characterized in terms of incorporation parameters and mean size. High Cuphen loadings were obtained and the presence of IONPs slightly reduced Cuphen incorporation parameters. Cuphen antiproliferative properties were preserved after association to liposomes and IONPs (at 2 mg/mL) did not interfere on cellular proliferation of murine and human melanoma cell lines. Moreover, the developed nanoformulations displayed magnetic properties. The absence of hemolytic activity for formulations under study demonstrated their safety for parenteral administration. In conclusion, a lipid-based nanosystem loading the cytotoxic metallodrug, Cuphen, and displaying magnetic properties was successfully designed.
Highlights
Melanoma, which derives from the malignant transformation of melanocytes, is one of most aggressive forms of skin cancer [1]
Long circulating and pH-sensitive liposomes with the lipid composition composed of dimiristoyl phosphatidyl choline (DMPC), cholesteryl hemisuccinate (CHEMS), and distearoyl phosphatidylethanolamine covalently linked to poly 2000 (DSPE-PEG), DMPC:CHEMS:DSPE-PEG, at a molar ratio of 57:38:5, were prepared by the dehydration-rehydration method [8,9,31]
The present study focused on melanoma treatment through a novel hybrid lipid-based nanosystem
Summary
Melanoma, which derives from the malignant transformation of melanocytes, is one of most aggressive forms of skin cancer [1]. Treatment options are primarily based on surgery, radiotherapy and chemotherapy. When the disease is detected at an early stage, the cure is often possible with surgery. When it progresses to the metastatic phase, the prognosis is poor, with low survival rates, and therapy usually fails. In these particular situations, combined systemic approaches are implemented, including targeted or non-targeted immunotherapy, chemo or and/or hormonal therapies [2,3,4].
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