PMID- 33011241
OWN - NLM
STAT- MEDLINE
DCOM- 20210707
LR  - 20220111
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 329
DP  - 2021 Jan 10
TI  - CCR2-targeted micelles for anti-cancer peptide delivery and immune stimulation.
PG  - 614-623
LID - S0168-3659(20)30570-8 [pii]
LID - 10.1016/j.jconrel.2020.09.054 [doi]
AB  - Signaling between the CC chemokine receptor 2 (CCR2) with its ligand, monocyte 
      chemoattractant protein-1 (MCP-1) promotes cancer progression by directly 
      stimulating tumor cell proliferation and downregulating the expression of 
      apoptotic proteins. Additionally, the MCP-1/CCR2 signaling axis drives the 
      migration of circulating monocytes into the tumor microenvironment, where they 
      mature into tumor-associated macrophages (TAMs) that promote disease progression 
      through induction of angiogenesis, tissue remodeling, and suppression of the 
      cytotoxic T lymphocyte (CTL) response. In order to simultaneously disrupt 
      MCP-1/CCR2 signaling and target CCR2-expressing cancer cells for drug delivery, 
      KLAK-MCP-1 micelles consisting of a CCR2-targeting peptide sequence (MCP-1 
      peptide) and the apoptotic KLAKLAK peptide were synthesized. In vitro, KLAK-MCP-1 
      micelles were observed to bind and induce cytotoxicity to cancer cells through 
      interaction with CCR2. In vivo, KLAK-MCP-1 micelles inhibited tumor growth 
      (34 +/- 11%) in a subcutaneous B16F10 murine melanoma model despite minimal tumor 
      accumulation upon intravenous injection. Tumors treated with KLAK-MCP1 
      demonstrated reduced intratumor CCR2 expression and altered infiltration of TAMs 
      and CTLs as evidenced by immunohistochemical and flow cytometric analysis. These 
      studies highlight the potential application of CCR2-targeted nanotherapeutic 
      micelles in cancer treatment.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Trac, Noah
AU  - Trac N
AD  - Department of Biomedical Engineering, University of Southern California, Los 
      Angeles, CA 90089, United States.
FAU - Chen, Leng-Ying
AU  - Chen LY
AD  - Lawrence J. Ellison Institute for Transformative Medicine, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA 90033, United 
      States.
FAU - Zhang, Ailin
AU  - Zhang A
AD  - Lawrence J. Ellison Institute for Transformative Medicine, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA 90033, United 
      States.
FAU - Liao, Chun-Peng
AU  - Liao CP
AD  - Lawrence J. Ellison Institute for Transformative Medicine, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA 90033, United 
      States.
FAU - Poon, Christopher
AU  - Poon C
AD  - Department of Biomedical Engineering, University of Southern California, Los 
      Angeles, CA 90089, United States.
FAU - Wang, Jonathan
AU  - Wang J
AD  - Department of Biomedical Engineering, University of Southern California, Los 
      Angeles, CA 90089, United States.
FAU - Ando, Yuta
AU  - Ando Y
AD  - Department of Biomedical Engineering, University of Southern California, Los 
      Angeles, CA 90089, United States.
FAU - Joo, Johan
AU  - Joo J
AD  - Department of Biomedical Engineering, University of Southern California, Los 
      Angeles, CA 90089, United States.
FAU - Garri, Carolina
AU  - Garri C
AD  - Lawrence J. Ellison Institute for Transformative Medicine, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA 90033, United 
      States.
FAU - Shen, Keyue
AU  - Shen K
AD  - Department of Biomedical Engineering, University of Southern California, Los 
      Angeles, CA 90089, United States; Norris Comprehensive Cancer Center, Keck School 
      of Medicine, University of Southern California, Los Angeles, CA 90089, United 
      States.
FAU - Kani, Kian
AU  - Kani K
AD  - Lawrence J. Ellison Institute for Transformative Medicine, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA 90033, United 
      States; Norris Comprehensive Cancer Center, Keck School of Medicine, University 
      of Southern California, Los Angeles, CA 90089, United States.
FAU - Gross, Mitchell E
AU  - Gross ME
AD  - Lawrence J. Ellison Institute for Transformative Medicine, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA 90033, United 
      States; Norris Comprehensive Cancer Center, Keck School of Medicine, University 
      of Southern California, Los Angeles, CA 90089, United States.
FAU - Chung, Eun Ji
AU  - Chung EJ
AD  - Department of Biomedical Engineering, University of Southern California, Los 
      Angeles, CA 90089, United States; Norris Comprehensive Cancer Center, Keck School 
      of Medicine, University of Southern California, Los Angeles, CA 90089, United 
      States; Division of Vascular Surgery and Endovascular Therapy, Department of 
      Surgery, Keck School of Medicine, University of Southern California, Los Angeles, 
      CA 90033, United States; Division of Nephrology and Hypertension, Department of 
      Medicine, Keck School of Medicine, University of Southern California, Los 
      Angeles, CA 90033, United States; Mork Family Department of Chemical Engineering 
      and Materials Science, University of Southern California, Los Angeles, CA 90089, 
      United States; Eli and Edythe Broad Center for Regenerative Medicine and Stem 
      Cell Research, Keck School of Medicine, University of Southern California, Los 
      Angeles, CA 90033, United States. Electronic address: eunchung@usc.edu.
LA  - eng
GR  - DP2 DK121328/DK/NIDDK NIH HHS/United States
GR  - R00 HL124279/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201001
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Micelles)
RN  - 0 (Peptides)
RN  - 0 (Receptors, CCR2)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Micelles
MH  - Monocytes
MH  - *Neoplasms
MH  - Peptides
MH  - *Receptors, CCR2
MH  - Tumor Microenvironment
PMC - PMC8491563
MID - NIHMS1635933
OTO - NOTNLM
OT  - CCR2
OT  - Cancer
OT  - Micelle
OT  - Peptide
OT  - Tumor-associated macrophage
EDAT- 2020/10/05 06:00
MHDA- 2021/07/08 06:00
PMCR- 2022/01/10
CRDT- 2020/10/04 20:23
PHST- 2020/07/07 00:00 [received]
PHST- 2020/09/18 00:00 [revised]
PHST- 2020/09/29 00:00 [accepted]
PHST- 2020/10/05 06:00 [pubmed]
PHST- 2021/07/08 06:00 [medline]
PHST- 2020/10/04 20:23 [entrez]
PHST- 2022/01/10 00:00 [pmc-release]
AID - S0168-3659(20)30570-8 [pii]
AID - 10.1016/j.jconrel.2020.09.054 [doi]
PST - ppublish
SO  - J Control Release. 2021 Jan 10;329:614-623. doi: 10.1016/j.jconrel.2020.09.054. 
      Epub 2020 Oct 1.