title: Coadministration of Oligomeric Hyaluronic Acid-Modified Liposomes with Tumor-Penetrating Peptide-iRGD Enhances the Antitumor Efficacy of Doxorubicin against Melanoma.
abstract: 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.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Deng
authors.affiliation: School of Pharmacy, Chengdu Medical College , Chengdu 610083, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Xun
authors.identifier: http://orcid.org/0000-0002-4671-352X
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Tao
authors.identifier: http://orcid.org/0000-0002-9866-9911
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Zhirong
authors.identifier: http://orcid.org/0000-0001-9118-5394
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin; D006820:Hyaluronic Acid; D008081:Liposomes; D008545:Melanoma; D051379:Mice; D010455:Peptides; D051381:Rats
chemical_list: D008081:Liposomes; D010455:Peptides; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: CD44 receptor; iRGD; liposomes; oligomeric hyaluronic acid; tumor targeting