Synthesis and evaluation of multivalent M2pep peptides for targeting alternatively activated M2 macrophages

Journal of Controlled Release : Official Journal of the Controlled Release Society
Chayanon NgambenjawongSuzie H Pun

Abstract

The tumor microenvironment in the majority of cancers is known to favor polarization of tumor-associated macrophages (TAMs) to alternatively activated M2 phenotype, promoting disease progression and reducing patient survival. Effective therapy targeting this M2 macrophage population is thus a promising adjuvant to approved cancer therapies. One of the challenges in targeting M2-like TAMs is a lack of high affinity targeting ligand with good selectivity over anti-tumor M1-like TAMs. We have previously identified an M2 macrophage-targeting peptide (M2pep) that binds preferentially to murine M2 macrophages and M2-like TAMs. A fusion peptide of M2pep with pro-apoptotic peptide KLA (M2pepKLA) was further used to reduce TAM population in vivo but high concentrations and frequent dosing were required due to low binding affinity of M2pep for M2 macrophage. The goal of this study was to develop more potent TAM depletion constructs by increasing the valency of both the M2pep targeting and KLA drug domains. Divalent and tetravalent displays of M2pep ([M2pep]2-Biotin and [M2pep]4-Biotin) were synthesized and evaluated for improvement in binding avidity to the murine macrophages. High avidity and selective binding of [M2pep]2-Biotin to M2 m...Continue Reading

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Citations

Jul 1, 2016·Cancer Nanotechnology·Rosemarie Truman, Cody J Locke
May 20, 2017·Nature Communications·Eric SongW Mark Saltzman
Jan 22, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Seok-Beom YongYong-Hee Kim
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Feb 13, 2018·ACS Biomaterials Science & Engineering·Chayanon Ngambenjawong, Suzie H Pun

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