Smart Lipid-Polysaccharide Nanoparticles for Targeted Delivery of Doxorubicin to Breast Cancer Cells.

Manuela Curcio,Vittoria Rago,Fiore Pasquale Nicoletta,Matteo Brindisi,Francesca Iemma,Giuseppe Cirillo,Anna Rita Cappello,Antonella Leggio,Luca Frattaruolo

doi:10.3390/ijms23042386

Manuela Curcio, Vittoria Rago + Show 7 more

Open Access

https://doi.org/10.3390/ijms23042386

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Abstract

In this study, actively-targeted (CD44-receptors) and dual stimuli (pH/redox)-responsive lipid–polymer nanoparticles were proposed as a delivery vehicle of doxorubicin hydrochloride in triple negative breast cancer cell lines. A phosphatidylcholine lipid film was hydrated with a solution of oxidized hyaluronic acid and doxorubicin, chosen as model drug, followed by a crosslinking reaction with cystamine hydrochloride. The obtained spherical nanoparticles (mean diameter of 30 nm) were found to be efficiently internalized in cancer cells by a receptor-mediated endocytosis process, and to modulate the drug release depending on the pH and redox potential of the surrounding medium. In vitro cytotoxicity assays demonstrated the safety and efficacy of the nanoparticles in enhancing the cytotoxic effect of the free anticancer drug, with the IC50 values being reduced by two and three times in MDA-MB-468 and MDA-MB-231, respectively. The combination of self-assembled phospholipid molecules with a polysaccharide counterpart acting as receptor ligand, and stimuli-responsive chemical moieties, was carried out on smart multifunctional nanoparticles able to actively target breast cancer cells and improve the in vitro anticancer activity of doxorubicin.

Highlights

Redox-sensitive and CD44 receptor-targeted nanoparticles were fabricated by a modified thin film method employing PDC and oxHA as phospholipid and polymeric components, respectively, and Cys as disulfide bonds-containing specimen (Figure 1a)
The results clearly proved that the pretreatment with hyaluronic acid (HA) was able to compete with the DOX@phospholipid–polysaccharide nanoparticle architecture (PHYN) uptake, confirming the nanoparticles’ CD44-mediated internalization mechanism
Our results show that the cytotoxic effect mediated by DOX@PHYN in MCF-10A, follows a comparable trend to that highlighted by free DOX (Figure 6d and Table 2), while a marked reduction in IC50 values was observed in both cancer cell lines, with values decreasing almost two- (MDA-MB-468, Figure 6c) and three- fold (MDA-MB-231, Figure 6b), respectively

Summary

Introduction

Radiotherapy and chemotherapy are the common clinical approaches to eradicate and/or reduce the tumor mass, with the administration of anticancer drugs typically accompanied by severe side effects related to their poor selectivity, and by the insurgence of multidrug resistance [2], affecting the success of the treatment.

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