Abstract
Personalized treatment strategies have greatly improved the efficacy of anticancer drugs. Nanocarriers, especially liposomes, function as excellent platform for the delivery of both hydrophilic and hydrophobic agents. iRGD is a peptide composed of 9-amino acid denoted as (iRGDP), enhances selective and intratumoral delivery of anticancer drugs. Trastuzumab (TMAB), mainly targets HER2-positive advanced stage breast cancer is an FDA-approved monoclonal antibody. Gefitinib (GEB) is an anticancer drug, effective against metastatic breast cancer (MBC), while Lycorine hydrochloride (LCOH), a naturally derived compound, possess both anti-inflammatory and anticancer properties. This research is mainly emphasizing on the preparation of GEB and LCOH-entrapped TPGS-COOH coated-liposomes, camouflaged with an antibody (TMAB) and cyclic peptide (iRGDP) for targeted delivery in MBC therapy. The developed multifunctional liposomes were studied for extensive in vitro cell line studies on MCF-7 cells. The half-maximum inhibitory concentration (IC-50) values of GEB and LCOH co-loaded single functionalized liposome (SFL) (iRGDP-LiP, and TMAB-LiP) and dual-functionalized liposome (DFL) (iRGDP-TMAB-LiP) on MCF-7 cells were 1.04 ± 0.023 μg/mL, 0.71 ± 0.018 μg/mL, and 0.56 ± 0.028 μg/mL, respectively. Inverted confocal laser scanning microscopy (ICLSM) revealed enhanced cellular internalization in SFL and DFL-treated groups tagged with coumarin-6 and rhodamine-B dye as compared to conventional liposome. The scratch assay revealed a marked reduction in cell migration, while DAPI staining confirmed enhanced nuclear condensation (NC) and nuclear fragmentation (NF) in SFL and DFL-treated groups. Moreover, flow cytometry demonstrated enhanced early and late apoptosis in SFL and DFL groups. These findings indicate that GEB and LCOH co-loaded multifunctional liposome holds promise as a multifaceted therapeutic approach for MBC therapy.
Published Version
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