Folate receptor-mediated delivery of mitoxantrone-loaded solid lipid nanoparticles to breast cancer cells

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Granja, A (Author) Other; Nunes, C (Author) Other; Sousa, CT (Author) FCUP; Salette Reis (Author) FFUP

Journal

Title: Biomedicine & Pharmacotherapy

Vol. 154

ISSN: 0753-3322

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 18 Citations

Other information

Authenticus ID: P-00X-3Z8

DOI: 10.1016/j.biopha.2022.113525

Abstract (EN): The standard breast cancer therapy still faces major challenges due to non-specific tumor distribution and occurrence of dose-limiting adverse side-effects. Nanomedicine constitutes an appealing approach to improve the therapeutic index of different anti-cancer drugs. Given their biocompatibility, low-cost manufacture and easy surface modification, lipid nanoparticles, such as solid lipid nanoparticles (SLN), have a great potential for drug delivery in cancer therapy. In this work, SLN entrapping the antineoplastic drug Mitoxantrone (Mito) were developed and functionalized with Disteroylphosphatidylethanolamine-poly(ethylene glycol)-folic acid (DSPE-PEG-FA) ligand to improve blood circulation and tumor selectivity and limit the drug systemic side-effects. Nanoparticles presented adequate size and size distribution for intravenous injection and were stable for at least 6 months. Additionally, their hemocompatibility was demonstrated. Moreover, functionalized nanoparticles were able to improve the anti-cancer effect of the free drug, as assessed by the values of IC50 and the apoptotic effects in MCF-7 cells. Moreover, an enhanced cellular internalization of the functionalized SLN was demon-strated by confocal microscopy and flow cytometry studies. Finally, the cellular uptake of the SLN was found to occur via macropinocytosis and clathrin-mediated endocytosis, suggesting the involvement of (folate receptor) (FR)-mediated endocytosis. Overall these findings highlight that the developed SLN are efficient nanocarriers for the selective delivery of Mito to breast cancer cells.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10