ɑvβ3-targeted liposomal drug delivery system with attenuated immunogenicity enabled by linear pentapeptide for glioma therapy.

Abstract

Owing to the binding capacity to ɑvβ3 integrin overexpressed on glioma, vasculogenic mimicry and neovasculature, the peptide c(RGDyK) has been exploited pervasively to functionalize nanocarriers for targeted delivery of bioactives. The former study in our group substantiated the immunotoxicity of c(RGDyK)-modified liposome, and this unfavorable immunogenicity is known to compromise blood circulation, targeting efficacy and therapeutic outcome. Therefore, we need to find a superior alternative ligand in order to evade the exquisite immuno-sensitization. We developed mn by structure-guided peptide design and retro-inverso isomerization technique, which was experimentally substantiated to have exceptional binding affinity to ɑvβ3 integrin. Besides mn does not have affinity toward normal liver cells and kidney cells, which c(RGDyK) possesses in a certain degree. Warranting that mn and c(RGDyK) anchored ɑvβ3, we formulated peptide-tethered liposomes and investigated in vivo bio-fate. Compared with c(RGDyK)-modified liposome, mn-modified liposome presented longer blood circulation and reduced ingestion by Kupffer cells with decreased retention in liver accordingly, benefitting from attenuated anti-liposome IgG and IgM response elicited by multiple sequential doses. Those merits strengthened the anti-glioma efficacy of ɑvβ3-targeted doxorubicin-loaded liposomes, proving the importance of immunocompatibility in process of targeted drug delivery.

• Authors: Jinyang Li, Zhilan Chai, Jiasheng Lu, Cao Xie, Danni Ran, Songli Wang, Jianfen Zhou, Weiyue Lu
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 322 Pg. 542-554 (06 10 2020) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 32277962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Liposomes
• Doxorubicin

Topics

• Animals
• Brain Neoplasms (drug therapy)
• Cell Line, Tumor
• Doxorubicin (therapeutic use)
• Drug Delivery Systems
• Glioma (drug therapy)
• Liposomes (therapeutic use)
• Mice
• Mice, Nude