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

• Published in: Carbohydrate polymers Vol. 314; p. 120900
• Main Authors: Paoletti, L., Zoratto, N., Benvenuto, M., Nardozi, D., Angiolini, V., Mancini, P., Masuelli, L., Bei, R., Frajese, G.V., Matricardi, P., Nalli, M., Di Meo, C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-08-2023
• Subjects: Active targeting; Antineoplastic Agents - chemistry; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Curcumin - chemistry; Docetaxel - therapeutic use; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems; Estradiol; Estradiol - pharmacology; Female; Humans; Hyaluronan; Hyaluronic Acid - chemistry; MCF-7 Cells; Nanogels - therapeutic use; Nanohydrogels; Nanoparticles - chemistry; DD; SRB; 17-ES-Br; DL; HA-Rfv; DTX; Drug delivery; CvME; Rhod; Estradiol; RBA; DMEM; Hyaluronan; DDS; HA-ES; Nanohydrogels; EE; CUR; DAPI; Breast cancer; mERs; HA-CH; ES; NMP; NPs; TEA; NHs; HA; Active targeting; TEM; ABTS; ES-NHs
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2023.120900

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.
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