iNGR-modified PEG-PLGA nanoparticles that recognize tumor vasculature and penetrate gliomas.

Abstract

A major cross-cutting problem for glioma therapy is the poor extravasation and penetration of the payload drug in target glioma parenchyma. Here, to overcome these obstacles, a tumor vessel recognizing and tumor penetrating system is developed by functionalizating the poly (ethyleneglycol)-poly (L-lactic-co-glycolic acid) nanoparticles with an iNGR moiety (iNGR-NP). The nanoparticulate formulation is expected to achieve specific deep penetration in the tumor tissue by initially binding to aminopeptidase N, with iNGR proteolytically cleaved to CRNGR, and then bind with neuropilin-1 to mediate deep penetration in the tumor parenchyma. iNGR-NP exhibits significantly enhanced cellular uptake in human umbilical vein endothelial cells, improves the anti-proliferation and anti-tube formation abilities of paclitaxel in vitro. Following intravenous administration, iNGR-NP present favorable pharmacokinetic and tumor homing profiles. Glioma distribution and penetration assays confirm that iNGR-NP achieve the highest accumulation and deepest penetration at the glioma sites. The anti-glioma efficacy of paclitaxel-loaded iNGR-NP is verified by its improved anti-angiogenesis activity and the significantly prolonged survival time in mice bearing intracranial glioma. These evidences highlight the potential of iNGR-decorated nanoparticles in overcoming the leading edge problem in anti-glioma drug delivery.

• Authors: Ting Kang, Xiaoling Gao, Quanyin Hu, Di Jiang, Xingye Feng, Xue Zhang, Qingxiang Song, Lei Yao, Meng Huang, Xinguo Jiang, Zhiqing Pang, Hongzhuan Chen, Jun Chen
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 14 Pg. 4319-32 (May 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24565520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Coumarins
• Drug Combinations
• Laminin
• Oligopeptides
• Proteoglycans
• Thiazoles
• coumarin 6
• cysteinyl-arginyl-asparagyl-glycyl-arginyl-glycyl-prolyl-aspartyl-cysteine
• matrigel
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Collagen
• Paclitaxel

Topics

• Administration, Intravenous
• Animals
• Brain Neoplasms (blood supply, drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Collagen (pharmacology)
• Coumarins (metabolism)
• Drug Combinations
• Endocytosis (drug effects)
• Glioma (blood supply, drug therapy, pathology)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Kaplan-Meier Estimate
• Lactic Acid (chemistry)
• Laminin (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Nanoparticles (chemistry, ultrastructure)
• Neovascularization, Pathologic (drug therapy, pathology)
• Oligopeptides (chemistry)
• Paclitaxel (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Proteoglycans (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Spectroscopy, Near-Infrared
• Thiazoles (metabolism)
• Tissue Distribution (drug effects)
• Treatment Outcome