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ACS applied materials & interfaces v.9 no.2, 2017년, pp.1280 - 1292   SCI SCIE
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Coadministration of Oligomeric Hyaluronic Acid-Modified Liposomes with Tumor-Penetrating Peptide-iRGD Enhances the Antitumor Efficacy of Doxorubicin against Melanoma

Deng, Caifeng (Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, ); Zhang, Quan (School of Pharmacy, Chengdu Medical College, Chengdu 610083, ); Fu, Yao (Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, ); Sun, Xun (Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, ); Gong, Tao (Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, ); Zhang, Zhirong (Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, );
  • 초록  

    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. Graphic Abstract


  • 주제어

    oligomeric hyaluronic acid .   iRGD .   CD44 receptor .   tumor targeting .   liposomes.  

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