Encapsulation and Enhanced Release of Resveratrol from Mesoporous Silica Nanoparticles for Melanoma Therapy.

Diogo Marinheiro,Helena Oliveira,Bárbara J M L Ferreira,Párástu Oskoei,Ana L Daniel-Da-Silva

doi:10.3390/ma14061382

Abstract

Chemotherapy has limited success in the treatment of malignant melanoma due to fast development of drug resistance and the low bioavailability of chemotherapeutic drugs. Resveratrol (RES) is a natural polyphenol with recognized preventive and therapeutic anti-cancer properties. However, poor RES solubility hampers its bioactivity, thus creating a demand for suitable drug delivery systems to improve it. This work aimed to assess the potential of RES-loaded mesoporous silica nanoparticles (MSNs) for human melanoma treatment. RES was efficiently loaded (efficiency > 93%) onto spheroidal (size~60 nm) MSNs. The encapsulation promoted the amorphization of RES and enhanced the release in vitro compared to non-encapsulated RES. The RES release was pH-dependent and markedly faster at pH 5.2 (acid environment in some tumorous tissues) than at pH 7.4 in both encapsulated and bulk forms. The RES release from loaded MSNs was gradual with time, without a burst effect, and well-described by the Weibull model. In vitro cytotoxicity studies on human A375 and MNT-1 melanoma cellular cultures showed a decrease in the cell viability with increasing concentration of RES-loaded MSNs, indicating the potent action of the released RES in both cell lines. The amelanotic cell line A375 was more sensitive to RES concentration than the melanotic MNT-1 cells.

Highlights

0.05*for 24 h; # indicates indicates significant differences between control at p < 0.05 for 24 h; # indicates significant significant differences between control at p < 0.05 for 48 h; and + indicates significant differences between control at p < 0.05 differences between control at p < 0.05 for 48 h; and + indicates significant differences between for 72 h. (a) MNT-1 cells exposed to RES-loaded mesoporous silica nanoparticles (MSNs); (b) A375 cells exposed to RES-loaded MSNs; (c) MNT-1 cells control at p < 0.05 for 72 h. (a) MNT-1 cells exposed to RES-loaded MSNs; (b) A375 cells exposed to exposed to pristine
MSNs;MSNs; (e) MNT-1 cells exposed to bulk and (f) A375 cells
MSNs; (e) MNT-1 cells exposed to bulk RES and (f) A375 cells exposed to bulk RES

Summary

Introduction

Malignant melanoma is the deadliest form of skin cancer and one of the most challenging malignancies to treat, with a steeply rising incidence and poor prognosis in advanced stages [1]. The prevalence of melanoma has been continuously increasing worldwide [2,3], and despite representing only 1% of skin cancers, it results in a large majority of skin cancer-related deaths [4]. Chemotherapy is an important instrument in the treatment of metastatic melanoma and in the palliation of patients with resistance to immunotherapies [5,6,7]. Single-agent chemotherapy has seen limited success in melanoma treatment due to the fast development of drug resistance, poor targeting efficiency, and low bioavailability of most chemotherapeutic drugs [1,6]

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