Electrospun Membranes Designed for Burst Release of New Gold-Complexes Inducing Apoptosis of Melanoma Cells

Abstract

Two non-commercial metallic Au-based complexes were tested against one of the most aggressive malignant melanomas of the skin (MeWo cells), through cell viability and time-lapse live-cell imaging system assays. The tests with the complexes were carried out both in the form of free metallic complexes, directly in contact with the MeWo cell line culture, and embedded in fibers of Polycaprolactone (PCL) membranes produced by the electrospinning technique. Membranes functionalized with complexes were prepared to evaluate the efficiency of the membranes against the melanoma cells and therefore their feasibility in the application as an antitumoral patch for topical use. Both series of tests highlighted a very effective antitumoral activity, manifesting a very relevant cell viability inhibition after both 24 h and 48 h. In the case of the AuM1 complex at the concentration of 20 mM, melanoma cells completely died in this short period of time. A mortality of around 70% was detected from the tests performed using the membranes functionalized with AuM1 complex at a very low concentration (3 wt.%), even after 24 h of the contact period. The synthesized complexes also manifest high selectivity with respect to the MeWo cells. The peculiar structural and morphological organization of the nanofibers constituting the membranes allows for a very effective antitumoral activity in the first 3 h of treatment. Experimental points of the release profiles were perfectly fitted with theoretical curves, which easily allow interpretation of the kinetic phenomena occurring in the release of the synthesized complexes in the chosen medium.

Bottom-Up Strategy to Forecast the Drug Location and Release Kinetics in Antitumoral Electrospun Drug Delivery Systems

“…This is because the Fick model does not describe appropriately these types of systems. Semi-empirical models derived from the Weibull model, here reported in Equation (4), recently applied in literature [ 37 , 38 ] are more efficient to describe when two mechanisms of release occur. …”

“…The height images have been processed using the software NanoScope Analysis 1.40 (Bruker Corporation, Billerica, MA, USA) and elaborated via OriginPro software (OriginLab Corporation, Northampton, MA, USA). The elaboration of the height profile has been done in accordance with literature [ 37 ].…”

“…For AuM1, the phenyl group was tracked in the release medium to monitor drug release, as previously reported in literature [ 37 ]. By tracking the absorbance of the target group (phenyl for AuM1, R-N=N-R for Dacarbazine, and (NHC d )AuCl) of known quantities of the various active substances, the calibration curves are well described by the Lambert-Beer Equation (8).…”

Nanometric Mechanical Behavior of Electrospun Membranes Loaded with Magnetic Nanoparticles

“…The data were analysed with the same methodology reported by Naddeo et al [ 52 ]. The crystallinity of the samples was obtained according to Sownthari et al [ 53 ] by deconvoluting the spectra [ 54 , 55 ] and considering the crystalline and the amorphous area [ 56 ] under the diffractometric curve profile, in accordance with procedure already reported in literature [ 29 ].…”

“…for producing highly flexible, microporous nanomaterials that convincingly mimic the features of the extracellular matrix and human tissue in general. Moreover, the possibility to easily load different types of fillers in the electrospun matrix for all types of applications is attracting great attention because it represents a powerful method to direct the material toward a myriad of diversified performances, including smart functions [ 29 , 30 , 31 , 32 , 33 ]. Moreover, by properly functionalizing the nanoparticle surface, it is possible to control its hydrophilic/hydrophobic behavior (a crucial parameter for the dispersion in water and for cell uptake) [ 34 , 35 , 36 ].…”