Highly efficacious and specific anti-glioma chemotherapy by tandem nanomicelles co-functionalized with brain tumor-targeting and cell-penetrating peptides.

Abstract

Glioma is a highly challenging human malignancy as drugs typically exhibit a low blood-brain barrier (BBB) permeability as well as poor glioma selectivity and penetration. Here, we report that tandem nanomicelles co-functionalized with brain tumor-targeting and cell-penetrating peptides, Angiopep-2 and TAT, enable a highly efficacious and specific anti-glioma chemotherapy. Interestingly, tandem nanomicelles with 20 mol% Angiopep-2 and 10 mol% TAT linked via long and short poly(ethylene glycol)s, respectively, while maintaining a high glioma cell selectivity display markedly enhanced BBB permeation, glioma accumulation and penetration, and glioma cell uptake. We further show that docetaxel-loaded tandem nanomicelles have a long blood circulation time in mice and significantly better inhibit orthotopic U87MG human glioma than the corresponding Angiopep-2 single peptide-functionalized control, leading to an improved survival rate with little adverse effects. These tandem nanomicelles uniquely combining brain tumor-targeting and cell-penetrating functions provide a novel and effective strategy for targeted glioma therapy.

• Authors: Yaqin Zhu, Yu Jiang, Fenghua Meng, Chao Deng, Ru Cheng, Jian Zhang, Jan Feijen, Zhiyuan Zhong
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 278 Pg. 1-8 (05 28 2018) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 29596873 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Angiopep-2
• Antineoplastic Agents
• Cell-Penetrating Peptides
• Delayed-Action Preparations
• Gene Products, tat
• Micelles
• Peptides
• Docetaxel
• Polyethylene Glycols

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology, toxicity)
• Blood-Brain Barrier (metabolism)
• Brain Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell-Penetrating Peptides (chemistry)
• Delayed-Action Preparations
• Docetaxel (administration & dosage, pharmacology, toxicity)
• Drug Delivery Systems
• Female
• Gene Products, tat (chemistry)
• Glioma (drug therapy, pathology)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Micelles
• Nanoparticles
• Peptides (chemistry)
• Polyethylene Glycols (chemistry)
• Survival Rate
• Xenograft Model Antitumor Assays