Genistein-Chitosan Derivative Nanoparticles for Targeting and Enhancing the Anti-Breast Cancer Effect of Tamoxifen In Vitro

• Published in: Journal of pharmaceutical sciences Vol. 113; no. 8; pp. 2575 - 2583
• Main Authors: Xing, Yang, Shen, Weiguang, Sun, Chuan, Wang, Ruyi, Fan, Bo, Liang, Guixian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024
• Subjects: Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - chemistry; Antineoplastic Agents, Hormonal - pharmacology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Proliferation - drug effects; Chitosan - chemistry; Drug Carriers - chemistry; Drug Delivery Systems - methods; Drug Liberation; Female; Genistein; Genistein - administration & dosage; Genistein - chemistry; Genistein - pharmacology; Humans; MCF-7 Cells; Nanoparticles; Nanoparticles - chemistry; Polyphosphates - chemistry; Tamoxifen; Tamoxifen - administration & dosage; Tamoxifen - chemistry; Tamoxifen - pharmacology; Nanoparticles; Breast cancer; Tamoxifen; Genistein
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1016/j.xphs.2024.05.023

•G protein-coupled estrogen receptor plays an important role in tamoxifen resistance.•Genistein has affinity with G protein-coupled estrogen receptor.•Tamoxifen and genistein can synergistically inhibit the proliferation of breast cancer cells. Tamoxifen (TAM) is a classical anti-estrogenic drug that antagonizes estrogen by competitively binding to estrogen receptor α (ERα). However, drug resistance to TAM remains a significant challenge in breast cancer treatment. In this study, we aimed to design an actively targeted drug delivery system to enhance the proliferation inhibitory effects of TAM on ER positive breast cancer cells. Herein, chitosan (CS) was modified with genistein (GEN) to obtain the actively targeted GEN-CS. The TAM-loaded nanoparticles (TAM-GEN-CS-NPs) were constructed using an ionic-crosslinking method, with GEN-CS as the carrier material and sodium tripolyphosphate (TPP) as the crosslinking agent. As a result, TAM-GEN-CS-NPs exhibited a spherical morphology with an average size of 299.8 nm. The encapsulation efficiency and drug loading content were 85.77% and 14.13 µg/mg, respectively. Compared with free TAM, TAM-GEN-CS-NPs displayed obvious slow-release performance. In vitro cellular assays demonstrated that TAM-GEN-CS-NPs had active targeting and proliferation inhibitory effects on MCF-7 cells. The IC50 of TAM and TAM-GEN-CS-NPs were 10.25 µg/mL and 7.22 µg/mL, respectively. More importantly, the combination index (CI) value of TAM and GEN was less than 1, indicating synergistic effects. Therefore, TAM-GEN-CS-NPs hold the potential to enhance TAM therapy for breast cancer through active targeting and synergistic treatment strategies.