Polymalic acid chlorotoxin nanoconjugate for near-infrared fluorescence guided resection of glioblastoma multiforme.
Brain tumor surgery
Extreme NIR fluorescence
Fluorescent mini nano agent
Precision of tumor resection
Tri-leucine peptide
U87 glioblastoma mouse model
Journal
Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
22
08
2018
revised:
01
03
2019
accepted:
19
03
2019
pubmed:
2
4
2019
medline:
1
9
2020
entrez:
2
4
2019
Statut:
ppublish
Résumé
Maximal surgical resection of glioma remains the single most effective treatment. Tools to guide the resection while avoiding removal of normal brain tissues can aid surgeons in achieving optimal results. One strategy to achieve this goal is to rely upon interoperative fluorescence staining of tumor cells in vivo, that can be visualized by the surgeon during resection. Towards this goal we have designed a biodegradable fluorescent mini nano imaging agent (NIA) with high specificity for U87MG glioma cells and previously unmet high light emission. The NIA is the conjugate of polymalic acid (PMLA) with chlorotoxin for tumor targeting, indocyanine green (ICG) for NIR fluorescence and the tri-leucin peptide as fluorescence enhancer. PMLA as a multivalent platform carries several molecules of ICG and the other ligands. The NIA recognizes multiple sites on glioma cell surface, demonstrated by the effects of single and combined competitors. Systemic IV injection into xenogeneic mouse model carrying human U87MG glioblastoma indicated vivid tumor cell binding and internalization of NIA resulting in intensive and long-lasting tumor fluorescence. The NIA is shown to greatly improve tumor removal supporting its utility in clinical applications.
Identifiants
pubmed: 30933776
pii: S0142-9612(19)30173-5
doi: 10.1016/j.biomaterials.2019.03.029
pmc: PMC6574176
mid: NIHMS1525844
pii:
doi:
Substances chimiques
Malates
0
Nanoconjugates
0
Polymers
0
Scorpion Venoms
0
poly(malic acid)
0
Chlorotoxin
06UV5RFW57
Indocyanine Green
IX6J1063HV
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
146-159Subventions
Organisme : NCI NIH HHS
ID : R01 CA209921
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA188743
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206220
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA230858
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
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