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Colloids Surf B Biointerfaces. 2017 Aug 1;156:330-339. doi: 10.1016/j.colsurfb.2017.05.038. Epub 2017 May 15.

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

Author information

1
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
2
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China. Electronic address: gongtaoy@126.com.

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.

KEYWORDS:

Glioma targeting; Lycobetaine; Octreotide; Tumor-associated macrophages; nRGD

PMID:
28544965
DOI:
10.1016/j.colsurfb.2017.05.038
[Indexed for MEDLINE]

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