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EILDV-conjugated, etoposide-loaded biodegradable polymeric micelles directing to tumor metastatic cells overexpressing α4β1 integrin

In the present study, poly(ethylene glycol)-b-poly(ε-caprolactone) micelles loaded with etoposide (ETO) were formulated and further conjugated with pentapeptide Glu-Ile-Leu-Asp-Val (EILDV) to target α4β1 integrin receptor overexpressed on metastatic tumor cell. Using a distinct ratio of carboxyl-ter...

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Detalles Bibliográficos
Autores principales: Ukawala, Mukesh, Rajyaguru, Tushar, Chaudhari, Kiran, Manjappa, A. S., Murthy, R. S. R., Gude, Rajiv
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Vienna 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451974/
https://www.ncbi.nlm.nih.gov/pubmed/26069491
http://dx.doi.org/10.1007/s12645-011-0023-7
Descripción
Sumario:In the present study, poly(ethylene glycol)-b-poly(ε-caprolactone) micelles loaded with etoposide (ETO) were formulated and further conjugated with pentapeptide Glu-Ile-Leu-Asp-Val (EILDV) to target α4β1 integrin receptor overexpressed on metastatic tumor cell. Using a distinct ratio of carboxyl-terminated poly(ethylene glycol)-block-poly(ε-caprolactone) (HOOC–PEG-b-PCL) to methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone (CH(3)O–PEG-b-PCL) polymers, we formulated a series of micellar formulations having different surface densities of EILDV and observed optimum cellular uptake of micelles with 10% EILDV surface density by B16F10 cells. The cytotoxicity of EILDV-conjugated micelles was observed close to 1.5-fold higher than plain ETO after 72 h of drug incubation, demonstrating controlled release of drug inside the cell after enhanced intracellular uptake with the ability to selectively target cancer cells. In addition, EILDV-conjugated micelles inhibited the migration of B16F10 cells effectively compared with plain ETO and non-conjugated micellar formulations when cells were treated with equivalent cytotoxic concentration of the drug, i.e., IC(25). B16F10 cells treated with EILDV-conjugated micelles showed a significant reduction in the attachment of cells to the substrate-coated plate compared with non-conjugated micellar formulations, implying retention of the biological activity of EILDV after coupling to micelles. Furthermore, the in vivo experimental metastasis assay conducted on C57BL/6 mice demonstrated significant activity of EIDLV-conjugated micelles in the reduction of pulmonary metastatic nodule formation in both pretreatment and post-treatment methods. In conclusion, EIDLV-conjugated micelles showed higher efficacy in the treatment of metastasis and would be a promising approach in the treatment of metastasis.