Morin Hydrate Encapsulation and Release from Mesoporous Silica Nanoparticles for Melanoma Therapy

resumo

Melanoma incidence, a type of skin cancer, has been increasing worldwide. There is a strong need to develop new therapeutic strategies to improve melanoma treatment. Morin is a bioflavonoid with the potential for use in the treatment of cancer, including melanoma. However, therapeutic applications of morin are restrained owing to its low aqueous solubility and limited bioavailability. This work investigates morin hydrate (MH) encapsulation in mesoporous silica nanoparticles (MSNs) to enhance morin bioavailability and consequently increase the antitumor effects in melanoma cells. Spheroidal MSNs with a mean size of 56.3 & PLUSMN; 6.5 nm and a specific surface area of 816 m(2)/g were synthesized. MH was successfully loaded (MH-MSN) using the evaporation method, with a loading capacity of 28.3% and loading efficiency of 99.1%. In vitro release studies showed that morin release from MH-MSNs was enhanced at pH 5.2, indicating increased flavonoid solubility. The in vitro cytotoxicity of MH and MH-MSNs on human A375, MNT-1 and SK-MEL-28 melanoma cell lines was investigated. Exposure to MSNs did not affect the cell viability of any of the cell lines tested, suggesting that the nanoparticles are biocompatible. The effect of MH and MH-MSNs on reducing cell viability was time- and concentration-dependent in all melanoma cell lines. The A375 and SK-MEL-28 cell lines were slightly more sensitive than MNT-1 cells in both the MH and MH-MSN treatments. Our findings suggest that MH-MSNs are a promising delivery system for the treatment of melanoma.

palavras-chave

CELL-CYCLE ARREST; FACTOR-KAPPA-B; IN-VIVO; TARGETED DELIVERY; FLAVONOID MORIN; DRUG-DELIVERY; APOPTOSIS; GROWTH; BIOAVAILABILITY; PROLIFERATION

categoria

Biochemistry & Molecular Biology; Chemistry

autores

Cunha, C; Marinheiro, D; Ferreira, BJML; Oliveira, H; Daniel-da-Silva, AL

Grupos

G1 - Materiais Porosos e Nanossistemas

Projectos

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

HOTsPOT - Novel upconversion nanoparticles for multimodal therapy of melanoma: pHOtothermal Therapy, PhOtodynamic therapy and chemoTherapy (HOTsPOT)

agradecimentos

This work was developed within the scope of the project CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020) and CESAM (UIDP/50017/2020 and UIDB/50017/2020 and LA/P/0094/2020), financed by national funds through the FCT/MCTES (PIDDAC). This work was supported by the project PTDC/BTM-MAT/31794/2017 (POCI-01-0145-FEDER-031794), funded by FEDER, through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI)-and by national funds (OE), through FCT/MCTES. The position held by B.J.M.L.F. was funded by national funds (OE), through FCT-Fundacao para a Ciencia e Tecnologia, I.P., in the scope of the framework contract foreseen in numbers 4, 5 and 6 of Article 23 of the Decreet-Law 57/2016, of 29 August, changed by Law 57/2017 of 19 July. D.M. acknowledges FCT for the PhD grant (2021.05673.BD). H.O. acknowledges FCT for the research contract under Scientific Employment Stimulus (CEECIND/04050/2017).