Laminin receptor-targeted etoposide loaded polymeric micelles: a novel approach for the effective treatment of tumor metastasis.

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.

• Authors: Mukesh Ukawala, Kiran Chaudhari, Tushar Rajyaguru, A S Manjappa, R S R Murthy, Rajiv Gude
• Journal: Journal of drug targeting (J Drug Target) Vol. 20 Issue 1 Pg. 55-66 (Jan 2012) ISSN: 1029-2330 [Electronic] England
• PMID: 21967151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Micelles
• Polymers
• Receptors, Laminin
• Etoposide

Topics

• Animals
• Drug Delivery Systems (methods)
• Etoposide (administration & dosage, metabolism)
• Female
• Lung Neoplasms (drug therapy, metabolism, secondary)
• Melanoma, Experimental (drug therapy, metabolism, secondary)
• Mice
• Mice, Inbred C57BL
• Micelles
• Polymers (administration & dosage, metabolism)
• Random Allocation
• Receptors, Laminin (metabolism)
• Treatment Outcome