Upconversion Nanoparticles with Mesoporous Silica Coatings for Doxorubicin Targeted Delivery to Melanoma Cells

Melanoma is one of the most aggressive skin cancers and requires innovative therapeutic strategies to overcome the limitations of conventional therapies. In this work, upconversion nanoparticles coated with mesoporous silica and functionalized with folic acid (UCNP@mSiO₂-FA) were developed as a targeted nanocarrier system for the delivery of doxorubicin (DOX). The UCNPs were synthesized via thermal decomposition, coated with mesoporous silica shells, and functionalized with folic acid (FA) to enable receptor-mediated targeting. DOX was then loaded into the mesoporous silica coating by adsorption, yielding UCNP@mSiO₂-FA-DOX. The different UCNPs were characterized for size, composition, colloidal stability, and loading and release of DOX. This comprehensive physicochemical characterization confirmed a high DOX loading efficiency and a slightly increased drug release under acidic conditions, mimicking the tumour microenvironment. In vitro assays using four melanoma cell lines (A375, B16-F10, MNT-1, and SK-MEL-28) revealed an excellent biocompatibility of UCNP@mSiO₂-FA and a significantly higher cytotoxicity of UCNP@mSiO₂-FA-DOX compared to unloaded UCNPs, in a dose-dependent manner. Cell cycle analysis demonstrated G2/M phase arrest after treatment with UCNP@mSiO₂-FA-DOX, confirming its antiproliferative effect. Overall, UCNP@mSiO₂-FA-DOX represents a promising nanoplatform for targeted melanoma therapy, combining active tumour targeting and enhanced anticancer efficacy.