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  • Title: Laminin receptor-targeted etoposide loaded polymeric micelles: a novel approach for the effective treatment of tumor metastasis.
    Author: Ukawala M, Chaudhari K, Rajyaguru T, Manjappa AS, Murthy RS, Gude R.
    Journal: J Drug Target; 2012 Jan; 20(1):55-66. PubMed ID: 21967151.
    Abstract:
    BACKGROUND: Tumor-targeted delivery is a desirable approach to improve therapeutic outcome of anticancer drug due to enhanced efficacy and reduced toxicity. PURPOSE: The present study was aimed to target laminin receptor over-expressed tumor cells using YIGSR (Tyr-Ile-Gly-Ser-Arg) conjugated etoposide loaded micelles in the treatment of metastasis. METHODS: YIGSR conjugated micelles prepared using synthesized carboxyl and methoxy terminated poly(ethylene glycol)-b-poly(ϵ-caprolactone) block copolymers were evaluated for it efficacy against highly metastatic B16F10 cell lines conducting cytotoxicity, colony formation, cell migration, cellular uptake and flow cytometry studies. The in-vivo antimetastatic effect of micelles was evaluated using experimental metastatic model on C57BL/6 mice. RESULTS: YIGSR conjugated micelles of particle size 45.2±3.77 nm and zeta potential of-5.7±1.3 mV demonstrated enhanced cytotoxicity and cellular uptake with significant reduction in colony formation and cell migration activities compared to non-conjugated micelles. Furthermore, a markedly inhibition in lung colony formation was observed with these micelles. DISCUSSION: An enhanced cellular internalization of YIGSR conjugated micelles due to laminin receptor based endocytosis resulted in to higher cytotoxicity as well as antimetastatic effect against highly metastatic B16F10 cells. CONCLUSION: These studies indicate that YIGSR conjugated nanocarrier can be a promising approach in the treatment of tumor metastasis.
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