Lithocholic acid-tryptophan conjugate (UniPR126) based mixed micelle as a nano carrier for specific delivery of niclosamide to prostate cancer via EphA2 receptor.
Targeted delivery of chemotherapeutic agents is considered a prominent strategy for the treatment of cancer due to its site-specific delivery, augmented penetration, bioavailability, and improved therapeutic efficiency. In the present study, we employed UniPR126 as a carrier in a mixed nanomicellar delivery system to target and deliver anticancer drug NIC specifically to cancer cells via EphA2 receptors as these receptors are overexpressed in cancer cells but not in normal cells. The specificity of the carrier was confirmed from the significant enhancement in the uptake of coumarin-6 loaded mixed nanomicelle by EphA2 highly expressed PC-3 cells compared to EphA2 low expressed H4 cells. Further, niclosamide-loaded lithocholic acid tryptophan conjugate-based mixed nanomicelle has shown significant synergistic cytotoxicity in PC-3 but not in H4 cells. In vivo anticancer efficacy data in PC-3 xenograft revealed a significant reduction in the tumor volume (66.87%) with niclosamide-loaded lithocholic acid tryptophan conjugate nanomicelle, where pure niclosamide showed just half of the activity. Molecular signaling data by western blotting also indicated that niclosamide-loaded lithocholic acid tryptophan conjugate nanomicelle interfered with the EphA2 receptor signaling and inhibition of the Wnt/beta-catenin pathway and resulted in the synergistic anticancer activity compared to niclosamide pure drug.
['Jannu|Arun Kumar|AK|', 'Puppala|Eswara Rao|ER|', 'Gawali|Basveshwar|B|', 'Syamprasad|N P|NP|', 'Alexander|Amit|A|', 'Marepally|Srujan|S|', 'Chella|Naveen|N|', 'Gangasani|Jagadeesh Kumar|JK|', 'Naidu|V G M|VGM|']
D045744:Cell Line, Tumor D006801:Humans D008095:Lithocholic Acid D008297:Male D008823:Micelles D009534:Niclosamide D011471:Prostatic Neoplasms D036104:Receptor, EphA2 D014364:Tryptophan D060449:Wnt Signaling Pathway
Targeted delivery Bile acid Drug repurpose Ephrin type-A receptor 2 Wnt signalling