A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma. (January 2015)

• Record Type: Journal Article
• Authors: Dai, Wenbing; Fan, Yuchen; Zhang, Hua; Wang, Xueqing; Zhang, Qiang; Wang, Xinglin
• Is Part Of: Drug delivery. Volume 22:Number 1(2015:Jan.)
• Page Start: 10
• Page End: 20
• Publication Date: 2015-01
• Subjects: Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.3109/10717544.2014.903580
• Languages: English
• ISSNs: 1071-7544

Abstract

<abstract> <title>Abstract</title> <p>iRGD is a tumor tissue penetrating peptide due to its targeted binding of integrin and neuropilin-1 receptors. Whether iRGD carries the liposomes in a similar way as it penetrates the cancer drugs or conjugated drugs into tumor tissues and cells has not been fully defined. Here, iRGD-modified and doxorubicin-loaded sterically stabilized liposomes (iRGD-SSL-DOX) and passive liposomes (SSL-DOX) were prepared. A series of experiments were performed to evaluate the tissue penetration, cell penetration, tumor blood vessel damage and anti-tumor effect. The results of flow cytometry and confocal microscopy studies showed that iRGD-SSL-DOX with 5% DSPE-PEG₂₀₀₀-iRGD achieved higher cellular uptake level than that of SSL-DOX on B16 melanoma cells. iRGD-SSL-DOX also exhibited stronger cell growth inhibition in cytotoxicity experiments. The tumor penetrating effect of iRGD was further confirmed by imaging and cellular uptake studies <italic>in vivo</italic>, in which higher distribution of iRGD-modified liposomes in tumor tissue and tumor cells was observed. Moreover, iRGD-SSL-DOX displayed improved tumor growth inhibition and anti-angiogenesis with less systemic toxicity in an armpit B16 melanoma model. In conclusion, iRGD reserved its tumor-penetrating properties well when modified on the surface of liposomes at optimal density and iRGD-SSL-DOX would be a promising drug delivery system for active targeting tumor therapy.</p> </abstract>