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Objective: The objective of the study was to tackle the recurrence of prostate cancer (PCa) post-surgery and to re-sensitize the docetaxel (DTX)-resistant PC-3 cells to chemo-therapy using NIC. Significance: Prolonged DTX therapy leads to the emergence of chemo-resistance by overexpression of PI3K-AKT pathway in PCa along with tumor recurrence post-surgery. Suppression of this pathway could be essential in improving the anticancer activity of DTX and re-sensitizing the resistant cells. Method: Niclosamide (NIC), an anthelmintic drug has shown tremendous anticancer potential and has re-sensitized the resistant cells to various drugs. To mitigate the post-surgical tumor recurrence, an implant-based system facilitating the sustained release of DTX and NIC could be beneficial. DTX and NIC were incorporated within a nanofiber (NF) system to prevent on-site recurrence by local release and re-sensitize the DTX-resistant cells. Key findings: The fabricated DTX-NIC NF via electrospinning were 334 ± 96.14 nm in diameter and demonstrated sustained release profile till 6 d. Elevated mitochondrial damage, reactive oxygen species levels and apoptotic index revealed improvement in the cytotoxicity of DTX-NIC post incorporation into the NF owing to their sustained release profile. Re-sensitization of PC-3/DTX cells was observed by introduction of NIC which could be due to the suppression of p-Akt1, which was overexpressed in resistant cells. Conclusion: From superior activity of DTX-NIC NF and re-sensitization of resistant cells, we conclude that DTX-NIC NF could be a beneficial therapeutic regimen in preventing tumor recurrence in PCa. [ABSTRACT FROM AUTHOR]

AbstractPersonalized 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. [ABSTRACT FROM AUTHOR]