Coadministration of Oligomeric Hyaluronic Acid-Modified Liposomes with Tumor-Penetrating Peptide-iRGD Enhances the Antitumor Efficacy of Doxorubicin against Melanoma

• DOI: 10.1021/acsami.6b13738
• Publication Date: 2016-12-25T03:24:08Z
• Authors: Caifeng Deng; Quan Zhang; Yao Fu; Xun Sun; Tao Gong; Zhirong Zhang
• Keywords: Mice; Doxorubicin; Cell Line, Tumor; Liposomes; Animals; 02 engineering and technology; Hyaluronic Acid; Peptides; 0210 nano-technology; Melanoma; Rats; 3. Good health

A safe and efficient tumor-targeting strategy based on oligomeric hyaluronic acid (HA) modification and coadministration of tumor-penetrating peptide-iRGD was successfully developed. In this study, common liposomes (cLip) were modified by oligomeric HA to obtain HA-Lip. After injection into rats, HA-Lip showed good stealth in the bloodstream and lower liver distribution compared with cLip. Moreover, our HA-Lip could be internalized into B16F10 cells (CD44-overexpressing tumor cells) through HA-CD44 interaction. After systemic administration to B16F10 melanoma-bearing mice, HA-Lip showed an increased distribution in tumor due to the prolonged blood circulation time and the enhanced penetration and retention effect. When coadministered with iRGD, the tumor penetration of HA-Lip was significantly enhanced, which could promote HA-Lip internalization by tumors cells located in deep tumor regions through receptor-mediated endocytosis. Furthermore, doxorubicin (DOX)-loaded HA-Lip coadministering with iRGD showed much better antitumor effect compared to DOX-loaded cLip and DOX-loaded cLip in combination with iRGD. In systemic toxicity test, DOX-loaded HA-Lip could significantly decrease the cardiotoxicity and myelosuppression of DOX. Taken together, our results demonstrated that coadministration of oligomeric HA-modified liposomes with iRGD could be a promising treatment strategy for targeted therapy of melanoma.