A Novel Hybrid Nanosystem Integrating Cytotoxic and Magnetic Properties as a Tool to Potentiate Melanoma Therapy

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.

Hybrid Nanosystems for Biomedical Applications

“…The superparamagnetic properties of IONPs provide active drug targeting capabilities to liposomes by application of an external magnetic field, and these “magnetoliposomes” are widely successful as DDSs . Magnetic targeting improves magnetoliposomal DOX delivery efficacy in comparison to both liposomal and free DOX. − Magnetoliposomes have also been utilized to delivered curcumin, docetaxel, gemcitabine, cisplatin, and cuphen and have been reported effective for radical scavenging as well as treatment of diverse cancers. ,− Magnetoliposome-mediated chemotherapy can be further enhanced through active targeting ligands and moieties with endogenous stimulus sensitivity. ,,, Finally, one report describes a IONP/liposome-based docetaxel delivery system that displayed drug release in response to both an external magnetic field as well as NIR . As such, the development of magnetoliposomes has been a boon for targeted drug delivery.…”

Melanoma Management: From Epidemiology to Treatment and Latest Advances

“…The controlled delivery and targeting of loaded drugs at the cellular level overcoming the biological barriers is one of the added value of this type of option [43,44]. Currently, several types of nanosystems namely liposomes, solid lipid nanoparticles, and nanostructured lipid carriers and polymeric, metallic, and hybrid nanoparticles are under pre-clinical investigation [163][164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179]. Despite this, there is still no nanomedicine commercially available for patients with melanoma so far, being limited to volunteers in the different clinical trials.…”

The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

“…In these 2D culture assays, cytotoxicity, migration, invasion, protein expression, molecular characterization, and genetic/genomic characterization are rou-tinely investigated [75,90]. Within cytotoxicity tests, the most popular is, undoubtedly, the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay towards B16-F10, MNT-1 and A375 cell lines [91][92][93][94]. Notwithstanding, other colorimetric methods have also been used to evaluate cytotoxicity, such as the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay [95][96][97][98][99].…”