nRGD modified lycobetaine and octreotide combination delivery system to overcome multiple barriers and enhance anti-glioma efficacy.

Abstract

For glioma as one of the most common and lethal primary brain tumors, the presence of BBB, BBTB, vasculogenic mimicry (VM) channels and tumor-associated macrophages (TAMs) are key biological barriers. Here, a novel drug delivery system which could efficiently deliver drugs to glioma by overcoming multi-barriers and increase antitumor efficacy through multi-therapeutic mechanisms was well developed. In this study, a multi-target peptide nRGD was used to transport across the BBB, mediate tumor penetration and target TAMs. Lycobetaine (LBT) was adopted to kill glioma cells and octreotide (OCT) was co-delivered to inhibit VM channels and prevent angiogenesis. LBT-OCT liposomes (LPs) showed controlled release profile in vitro, increased uptake efficiency, improved inhibitory effect against glioma cells and VM formation, and enhanced BBB-crossing capability. The median survival time of glioma-bearing mice administered with LBT-OCT LPs-nRGD was significantly longer than LBT-OCT LPs (P<0.01). Besides, nRGD achieved a stronger inhibitory effect against tumor associated macrophages (TAMs) compared to LPs-iRGD treatment groups in vivo. Thus, LPs-nRGD represented a promising versatile delivery platform for combination drug therapy in glioma treatment.

• Authors: Tijia Chen, Xu Song, Ting Gong, Yao Fu, Liuqing Yang, Zhirong Zhang, Tao Gong
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 156 Pg. 330-339 (Aug 01 2017) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 28544965 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Amaryllidaceae Alkaloids
• Antineoplastic Agents, Hormonal
• Indolizines
• Oligopeptides
• ungeremine
• arginyl-glycyl-aspartic acid
• Octreotide

Topics

• Amaryllidaceae Alkaloids (chemistry, pharmacology)
• Animals
• Antineoplastic Agents, Hormonal (chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Central Nervous System Neoplasms (drug therapy, pathology)
• Drug Delivery Systems
• Glioma (drug therapy, pathology)
• Indolizines (chemistry, pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental (drug therapy, pathology)
• Neovascularization, Pathologic (drug therapy, pathology)
• Octreotide (chemistry, pharmacology)
• Oligopeptides (chemistry)
• Rats
• Rats, Sprague-Dawley
• Tumor Cells, Cultured