Novel CD44-Targeted Albumin Nanoparticles: An Innovative Approach to Improve Breast Cancer Treatment

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Oct 16

PMID 39408889

Authors

Giuseppe Cirillo

Anna Rita Cappello

Manuela Curcio

Marco Fiorillo

Luca Frattaruolo

Paola Avena

Ludovica Scorzafave

Vincenza Dolce

Fiore Pasquale Nicoletta

Francesca Iemma

Affiliations

Soon will be listed here.

Abstract

This study introduces novel CD44-targeted and redox-responsive nanoparticles (FNPs), proposed as doxorubicin (DOX) delivery devices for breast cancer. A cationized and redox-responsive Human Serum Albumin derivative was synthesized by conjugating Human Serum Albumin with cystamine moieties and then ionically complexing it with HA. The suitability of FNPs for cancer therapy was assessed through physicochemical measurements of size distribution (mean diameter of 240 nm), shape, and zeta potential (15.4 mV). Nanoparticles possessed high DOX loading efficiency (90%) and were able to trigger the drug release under redox conditions of the tumor environment (55% release after 2 h incubation). The use of the carrier increased the cytotoxic effect of DOX by targeting the CD44 protein. It was shown that, upon loading, the cytotoxic effect of DOX was enhanced in relation to CD44 protein expression in both 2D and 3D models. DOX@FNPs significantly decrease cellular metabolism by reducing both oxygen consumption and extracellular acidification rates. Moreover, they decrease the expression of proteins involved in the oxidative phosphorylation pathway, consequently reducing cellular viability and motility, as well as breast cancer stem cells and spheroid formation, compared to free DOX. This new formulation could become pioneering in reducing chemoresistance phenomena and increasing the specificity of DOX in breast cancer patients.

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