Hyaluronan-estradiol nanogels as potential drug carriers to target ER+ breast cancer cell line

L Paoletti; N Zoratto; M Benvenuto; D Nardozi; V Angiolini; P Mancini; L Masuelli; R Bei; G V Frajese; P Matricardi; M Nalli; C Di Meo

doi:10.1016/j.carbpol.2023.120900

Hyaluronan-estradiol nanogels as potential drug carriers to target ER+ breast cancer cell line

Carbohydr Polym. 2023 Aug 15:314:120900. doi: 10.1016/j.carbpol.2023.120900. Epub 2023 Apr 13.

Authors

L Paoletti¹, N Zoratto¹, M Benvenuto², D Nardozi³, V Angiolini³, P Mancini³, L Masuelli³, R Bei⁴, G V Frajese⁵, P Matricardi¹, M Nalli¹, C Di Meo⁶

Affiliations

¹ Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
² Saint Camillus International, University of Health and Medical Sciences, Via di Sant'Alessandro 8, 00131 Rome, Italy; Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
³ Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
⁴ Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
⁵ Department of Sports Science, Human and Health, University of Rome 'Foro Italico', Piazza Lauro De Bosis, 15, 00135 Rome, Italy.
⁶ Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. Electronic address: chiara.dimeo@uniroma1.it.

PMID: 37173041
DOI: 10.1016/j.carbpol.2023.120900

Abstract

An innovative hyaluronan-based nano-delivery system is proposed for the active targeting towards ER+ breast cancer. Hyaluronic acid (HA), an endogenous and bioactive anionic polysaccharide, is functionalized with estradiol (ES), a sexual hormone involved in the development of some hormone-dependent tumors, to give an amphiphilic derivative (HA-ES) able to spontaneously self-assemble in water to form soft nanoparticles or nanogels (NHs). The synthetic strategy used to obtain the polymer derivatives and the physico-chemical properties of the obtained nanogels (ES-NHs) are reported. ES-NHs ability to entrap hydrophobic molecules has also been investigated, by loading curcumin (CUR) and docetaxel (DTX), both able to inhibit the growth of ER+ breast cancer. The formulations are studied for their capability to inhibit the growth of the MCF-7 cell line, thus evaluating their efficacy and potential as a selective drug delivery systems. Our results demonstrate that ES-NHs have not toxic effects on the cell line, and that both ES-NHs/CUR and ES-NHs/DTX treatments inhibit MCF-7 cell growth, with ES-NHs/DTX effect higher than that of free DTX. Our findings support the use of ES-NHs to deliver drugs to ER+ breast cancer cells, assuming a receptor-dependent targeting.

Keywords: Active targeting; Breast cancer; Drug delivery; Estradiol; Hyaluronan; Nanohydrogels.

MeSH terms

Antineoplastic Agents* / chemistry
Breast Neoplasms* / drug therapy
Breast Neoplasms* / pathology
Cell Line, Tumor
Curcumin* / chemistry
Docetaxel / therapeutic use
Drug Carriers / chemistry
Drug Delivery Systems
Estradiol / pharmacology
Female
Humans
Hyaluronic Acid / chemistry
MCF-7 Cells
Nanogels / therapeutic use
Nanoparticles* / chemistry

Substances

Drug Carriers
Hyaluronic Acid
Nanogels
Estradiol
Docetaxel
Curcumin
Antineoplastic Agents