PMID- 30933776
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20231012
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Print)
IS  - 0142-9612 (Linking)
VI  - 206
DP  - 2019 Jun
TI  - Polymalic acid chlorotoxin nanoconjugate for near-infrared fluorescence guided 
      resection of glioblastoma multiforme.
PG  - 146-159
LID - S0142-9612(19)30173-5 [pii]
LID - 10.1016/j.biomaterials.2019.03.029 [doi]
AB  - 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.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Patil, Rameshwar
AU  - Patil R
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Galstyan, Anna
AU  - Galstyan A
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Sun, Tao
AU  - Sun T
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Shatalova, Ekaterina S
AU  - Shatalova ES
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Butte, Pramod
AU  - Butte P
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Mamelak, Adam N
AU  - Mamelak AN
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Carico, Christine
AU  - Carico C
AD  - The University of Alabama at Birmingham, Birmingham, AL, United States.
FAU - Kittle, David S
AU  - Kittle DS
AD  - Blaze Bioscience, Inc. Seattle, Washington, United States.
FAU - Grodzinski, Zachary B
AU  - Grodzinski ZB
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Chiechi, Antonella
AU  - Chiechi A
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Ding, Hui
AU  - Ding H
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Black, Keith L
AU  - Black KL
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Ljubimova, Julia Y
AU  - Ljubimova JY
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States.
FAU - Holler, Eggehard
AU  - Holler E
AD  - Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical 
      Center, Los Angeles, CA, United States. Electronic address: 
      eggehard.holler@cshs.org.
LA  - eng
GR  - R01 CA209921/CA/NCI NIH HHS/United States
GR  - R01 CA188743/CA/NCI NIH HHS/United States
GR  - R01 CA206220/CA/NCI NIH HHS/United States
GR  - R01 CA230858/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190323
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Malates)
RN  - 0 (Nanoconjugates)
RN  - 0 (Polymers)
RN  - 0 (Scorpion Venoms)
RN  - 0 (poly(malic acid))
RN  - 06UV5RFW57 (Chlorotoxin)
RN  - IX6J1063HV (Indocyanine Green)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Female
MH  - Glioblastoma/*surgery
MH  - Humans
MH  - Indocyanine Green/chemistry
MH  - Malates/*chemistry
MH  - Mice
MH  - Nanoconjugates/*chemistry
MH  - Polymers/*chemistry
MH  - Scorpion Venoms/*chemistry
MH  - Spectroscopy, Near-Infrared
MH  - Xenograft Model Antitumor Assays
PMC - PMC6574176
MID - NIHMS1525844
OTO - NOTNLM
OT  - Brain tumor surgery
OT  - Extreme NIR fluorescence
OT  - Fluorescent mini nano agent
OT  - Precision of tumor resection
OT  - Tri-leucine peptide
OT  - U87 glioblastoma mouse model
COIS- Competing financial interests The authors declare competing financial interests: 
      details are available in the online version of the paper. K.L.B., J.Y.L and E.H. 
      are shareholders of Arrogene, Inc.
EDAT- 2019/04/02 06:00
MHDA- 2020/09/01 06:00
PMCR- 2020/06/01
CRDT- 2019/04/02 06:00
PHST- 2018/08/22 00:00 [received]
PHST- 2019/03/01 00:00 [revised]
PHST- 2019/03/19 00:00 [accepted]
PHST- 2019/04/02 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2019/04/02 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - S0142-9612(19)30173-5 [pii]
AID - 10.1016/j.biomaterials.2019.03.029 [doi]
PST - ppublish
SO  - Biomaterials. 2019 Jun;206:146-159. doi: 10.1016/j.biomaterials.2019.03.029. Epub 
      2019 Mar 23.