Fluorescent Silica Nanoparticles Targeting Mitochondria: Trafficking in Myeloid Cells and Application as Doxorubicin Delivery System in Breast Cancer Cells

Abstract

Fluorescent silica nanoparticles (SiNPs) appear to be a promising imaging platform, showing a specific subcellular localization. In the present study, we first investigated their preferential mitochondrial targeting in myeloid cells, by flow cytometry, confocal microscopy and TEM on both cells and isolated mitochondria, to acquire knowledge in imaging combined with therapeutic applications. Then, we conjugated SiNPs to one of the most used anticancer drugs, doxorubicin (DOX). As an anticancer agent, DOX has high efficacy but also an elevated systemic toxicity, causing multiple side effects. Nanostructures are usually employed to increase the drug circulation time and accumulation in target tissues, reducing undesired cytotoxicity. We tested these functionalized SiNPs (DOX-NPs) on breast cancer cell line MCF-7. We evaluated DOX-NP cytotoxicity, the effect on the cell cycle and on the expression of CD44 antigen, a molecule involved in adhesion and in tumor invasion, comparing DOX-NP to free DOX and stand-alone SiNPs. We found a specific ability to release a minor amount of CD44+ extracellular vesicles (EVs), from both CD81 negative and CD81 positive pools. Modulating the levels of CD44 at the cell surface in cancer cells is thus of great importance for disrupting the signaling pathways that favor tumor progression.

Extracellular Vesicles as New Players in Drug Delivery: A Focus on Red Blood Cells-Derived EVs

“…Our experience is specifically related to fluorescent silica nanoparticles (SiNPs), which appear to be a promising imaging platform and show a specific subcellular localization that is mainly at the mitochondrial level. We conjugated SiNPs to one of the most commonly used anticancer drugs, doxorubicin, and we tested these functionalized SiNPs (DOX-NPs) on the breast cancer cell line MCF-7 [ 77 ]. Generally, carrier nanoparticles (NPs) reveal a poor penetration capacity and an inadequate balance between drug retention in the bloodstream and drug release at the specific pathologic body districts [ 78 ].…”

Flow Cytometry and Its Applications to Molecular Biology and Diagnosis 2.0

“…In this regard, fluorescent silica nanoparticles (SiNPs) appear to be a promising imaging platform, as they show intramitochondrial colocalization in biological cell models and can be used as efficient drug delivery systems when conjugated to a therapeutic molecule. Sola et al [9] performed an experimental study aimed to characterize the intracellular targeting of SiNPs in myeloid cell lines and the cytotoxicity and cellular effects of doxorubicin-conjugated SiNPs (DOX-NPs) on the breast cancer line MCF-7. Their results indicated that DOX-NPs are endocytosed and co-localize with lysosomes, inducing a cell cycle arrest and promoting apoptosis.…”