TY - JOUR
T1 - Protein Mimetic and Anticancer Properties of Monocyte-Targeting Peptide Amphiphile Micelles
AU - Poon, Christopher
AU - Chowdhuri, Sampreeti
AU - Kuo, Cheng Hsiang
AU - Fang, Yun
AU - Alenghat, Francis J.
AU - Hyatt, Danielle
AU - Kani, Kian
AU - Gross, Mitchell E.
AU - Chung, Eun Ji
N1 - Funding Information:
We thank Mr. Johan Joo and Miss Shivani Gupta for experimental assistance. We also thank Dr. Matthew Tirrell for his helpful discussion. This work was supported by the University of Southern California, the National Heart, Lung, and Blood Institute (NHLBI), R00HL124279, Eli and Edythe Broad Innovation Award, and the L.K. Whittier Foundation Non-Cancer Translational Research Award granted to E.J.C. We thank the Center for Research Informatics at the Univeristy of Chicago for experimental assistance and the Center for Electron Microscopy and Microanalysis, Center of Excellence in Nano-Biophysics, Center of Excellence for Molecular Characterization, and Translational Imaging Center at the University of Southern California for assistance in instrument setups.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/12/11
Y1 - 2017/12/11
N2 - Monocyte chemoattractant protein-1 (MCP-1) stimulates the migration of monocytes to inflammatory sites, leading to the progression of many diseases. Recently, we described a monocyte-targeting peptide amphiphile micelle (MCP-1 PAM) incorporated with the chemokine receptor CCR2 binding motif of MCP-1, which has a high affinity for monocytes in atherosclerotic plaques. We further report here the biomimetic components of MCP-1 PAMs and the influence of the nanoparticle upon binding to monocytes. We report that MCP-1 PAMs have enhanced secondary structure compared to the MCP-1 peptide. As a result, MCP-1 PAMs displayed improved binding and chemoattractant properties to monocytes, which upregulated the inflammatory signaling pathways responsible for monocyte migration. Interestingly, when MCP-1 PAMs were incubated in the presence of prostate cancer cells in vitro, the particle displayed anticancer efficacy by reducing CCR2 expression. Given that monocytes play an important role in tumor cell migration and invasion, our results demonstrate that PAMs can improve the native biofunctional properties of the peptide and may be used as an effective inhibitor to prevent chemokine-receptor interactions that promote disease progression.
AB - Monocyte chemoattractant protein-1 (MCP-1) stimulates the migration of monocytes to inflammatory sites, leading to the progression of many diseases. Recently, we described a monocyte-targeting peptide amphiphile micelle (MCP-1 PAM) incorporated with the chemokine receptor CCR2 binding motif of MCP-1, which has a high affinity for monocytes in atherosclerotic plaques. We further report here the biomimetic components of MCP-1 PAMs and the influence of the nanoparticle upon binding to monocytes. We report that MCP-1 PAMs have enhanced secondary structure compared to the MCP-1 peptide. As a result, MCP-1 PAMs displayed improved binding and chemoattractant properties to monocytes, which upregulated the inflammatory signaling pathways responsible for monocyte migration. Interestingly, when MCP-1 PAMs were incubated in the presence of prostate cancer cells in vitro, the particle displayed anticancer efficacy by reducing CCR2 expression. Given that monocytes play an important role in tumor cell migration and invasion, our results demonstrate that PAMs can improve the native biofunctional properties of the peptide and may be used as an effective inhibitor to prevent chemokine-receptor interactions that promote disease progression.
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U2 - 10.1021/acsbiomaterials.7b00600
DO - 10.1021/acsbiomaterials.7b00600
M3 - Article
AN - SCOPUS:85038211787
SN - 2373-9878
VL - 3
SP - 3273
EP - 3282
JO - ACS Biomaterials Science and Engineering
JF - ACS Biomaterials Science and Engineering
IS - 12
ER -