Thursday, 04 June 2020 10:51

mUNO peptide targets M2-TAMs in primary and metastatic breast tumors.

Lymph node imaging in metastatic dissemination Top: Whole lymph node fluorescence imaging of mice with metastasized breast tumors, injected with two different probes: a validated tumor lymph node targeting agent (top right), and mUNO (top left). Bottom: the signal from mUNO (green) in the lymph node associated with M2 macrophages (red). Authors: Anni Lepland, Pablo Scodeller. Lymph node imaging in metastatic dissemination Top: Whole lymph node fluorescence imaging of mice with metastasized breast tumors, injected with two different probes: a validated tumor lymph node targeting agent (top right), and mUNO (top left). Bottom: the signal from mUNO (green) in the lymph node associated with M2 macrophages (red). Authors: Anni Lepland, Pablo Scodeller.

Our collaborative study, published in Molecular Pharmaceutics describes the application of a short linear peptide (CSPGAK, "m(ini)UNO") for the delivery of molecular and nanoscale cargoes in M2-like tumor associated macrophages in vitro and the relevance of the peptide for in vivo targeting of early-stage primary breast tumors and metastatic lung foci.

This important study provides additional mechanistic understanding of mUNO binding and internalization pathway, addresses the effect of route of administration on the peptide bioavailability, and shows the robust accumulation of mUNO in M2-skewed macrophages in mouse models of early primary breast tumor and lung metastasis. This work also illustrates that mUNO can serve as a diagnostic probe for metastatic dissemination, by guiding an imaging agent to M2 macrophages in tumor and lymph node, more sensitively than an established tumor lymph node targeting agent.These studies support application of mUNO peptide for delivery of molecular and nanoscale cargoes to M2 macrophages in primary and metastatic breast tumors.

Lepland A, Asciutto EK, Malfanti A, Simón-Gracia L, Sidorenko V, Vicent MJ, Teesalu T, Scodeller P. Targeting Pro-Tumoral Macrophages in Early Primary and Metastatic Breast Tumors with the CD206-Binding mUNO Peptide. Mol Pharm. 2020 Jun 1. doi: 10.1021/acs.molpharmaceut.0c00226

https://pubmed.ncbi.nlm.nih.gov/32421341