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

Yaqin Zhu, Yu Jiang, Fenghua Meng, Chao Deng, Ru Cheng, Jian Zhang (Corresponding Author), Jan Feijen (Corresponding Author), Zhiyuan Zhong (Corresponding Author)

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalJournal of controlled release
Volume278
DOIs
Publication statusPublished - 28 May 2018

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Cell-Penetrating Peptides
Brain Neoplasms
Glioma
Drug Therapy
docetaxel
Blood-Brain Barrier
Blood Circulation Time
Ethylene Glycol
Permeability
Peptides

Keywords

  • UT-Hybrid-D
  • Glioma
  • Nanomicelles
  • Reduction-sensitive
  • TAT
  • Blood-brain barrier

Cite this

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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.",
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Highly efficacious and specific anti-glioma chemotherapy by tandem nanomicelles co-functionalized with brain tumor-targeting and cell-penetrating peptides. / Zhu, Yaqin; Jiang, Yu; Meng, Fenghua; Deng, Chao; Cheng, Ru; Zhang, Jian (Corresponding Author); Feijen, Jan (Corresponding Author); Zhong, Zhiyuan (Corresponding Author).

In: Journal of controlled release, Vol. 278, 28.05.2018, p. 1-8.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Jiang, Yu

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AU - Deng, Chao

AU - Cheng, Ru

AU - Zhang, Jian

AU - Feijen, Jan

AU - Zhong, Zhiyuan

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