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.

Keywords::

• Polymeric micelles
• YIGSR
• block copolymer
• etoposide
• metastasis
• cell uptake

Acknowledgment

The authors are thankful to Mr. Manohar Parkar and Mr. Yuvaraj Nikam for their kind assistance in cell line and animal studies conducted at ACTREC, respectively.

Declaration of interest

This work was supported by grants from the Indian Council of Medical Research (ICMR) New Delhi. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.