期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 215, 期 -, 页码 334-345出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2022.06.095
关键词
Redox responsive micelles; Gellan gum; Abietic acid
资金
- Isfahan University of Medical Sciences
In this study, a redox-sensitive micelle was designed for targeted delivery of Ribociclib to breast cancer cells. The micelle showed promising redox sensitivity and high cytotoxicity.
In most breast tumors level of glutathione reductase is much higher than in healthy tissues. In the current study, a redox-glutathione sensitive micelle based on Abietic acid-Cystamine-Gellan gum (AB-ss-GG) was designed for targeted delivery of Ribociclib (RIB) to breast cancer cells. AB is a monocarboxylic acid and a diterpenoid abietane with anti-tumor effects. Successful synthesis of the conjugate was confirmed by FT-IR and 1HNMR spectroscopy. Critical micelle concentration (CMC) was measured by pyrene as a fluorescent probe. Micelles of AB-GG and AB-ss-GG were loaded with different RIB/polymer ratios, and their redox-sensitivity was measured in the presence and absence of dithiothreitol (DTT) by determining the particle size and RIB release efficiency. Cell cytotoxicity and cellular uptake were assessed by MTT assay and flow-cytometry method on MCF-7 cells. CMC of AB-ss-GG and AB-GG micelles were estimated to be 40.15 and 37.33 mg/mL, respectively. In the presence of DTT, the particle size and release efficiency of AB-ss-GG micelles increased specially at a 1:1 drug/polymer ratio. AB-ss-GG micelles containing RIB showed higher cytotoxicity (IC50 = 47.86 mu mol/L) and cellular uptake than AB -GG micelles (IC50 = 190.25 mu mol/L) and free RIB (IC50 = 75.26 mu mol/L) at 48 h. AB-ss-GG micelles showed a promising redox-sensitive polymeric carrier for RIB delivery.
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