Targeted delivery of RGD-modified liposomes encapsulating both combretastatin A-4 and doxorubicin for tumor therapy: in vitro and in vivo studies - PubMed (original) (raw)

Targeted delivery of RGD-modified liposomes encapsulating both combretastatin A-4 and doxorubicin for tumor therapy: in vitro and in vivo studies

Yi-Fei Zhang et al. Eur J Pharm Biopharm. 2010 Mar.

Abstract

Arg-Gly-Asp (RGD) modified doxorubicin-loaded liposomes could improve anticancer effect, and vascular disrupting agents (VDAs) could induce a rapid and selective shutdown of the blood vessels of tumors. We propose that RGD-modified liposomes for co-encapsulation and sequential release of vascular disrupting agent combretastatin A-4 (CA-4) and cytotoxic agent doxorubicin (Dox) could enhance tumor inhibition responses. In this study, we encapsulated Dox and CA-4 in RGD-modified liposomes. The release rate of Dox was proved to be much slower than that of CA-4 in vitro. Flow cytometry and laser confocal scanning microscopy clearly showed that RGD-modification promoted intracellular uptake of liposomal drugs by B16/B16F10 melanoma tumor cells and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assay showed that the IC(50) of RGD-modified liposomes was lower than that of the corresponding unmodified liposomes. Therapeutic benefits were examined on B16F10 melanoma tumors subcutaneously growing in C57BL/6 mice. In vivo study demonstrated that RGD-modified liposomes exhibited the most pronounced tumor regression effect when both CA-4 and Dox were co-encapsulated. These results suggest that the targeted drug delivery system for co-encapsulation of vascular disrupting agents and anticancer agents may be a promising strategy for cancer treatment.

(c) 2010 Elsevier B.V. All rights reserved.

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