biostudies-literatureLepland AEesti TeadusagentuurUniversità di PadovaEstonian Research CouncilEstonian Research AgencyRamon y CajalMSCA-RISE 2018 Project OXIGENATED, and EuronanomedIII"ERDF A way of making Europe"Royal Society of ChemistryMICIN/AEIMCIN/AEI /10.13039/501100011033/CIBER BBNe2410288https://www.ebi.ac.uk/biostudies/studies/S-EPMC11904948biostudies-literatureUnknown12(10)In triple-negative breast cancer (TNBC), pro-tumoral macrophages promote metastasis and suppress the immune response. To target these cells, a previously identified CD206 (mannose receptor)-binding peptide, mUNO was engineered to enhance its affinity and proteolytic stability. The new rationally designed peptide, MACTIDE, includes a trypsin inhibitor loop, from the Sunflower Trypsin Inhibitor-I. Binding studies to recombinant CD206 revealed a 15-fold lower K_D for MACTIDE compared to parental mUNO. Mass spectrometry further demonstrated a 5-fold increase in MACTIDE's half-life in tumor lysates compared to mUNO. Homing studies in TNBC-bearing mice shows that fluorescein (FAM)-MACTIDE precisely targeted CD206⁺ tumor-associated macrophages (TAM) upon intravenous, intraperAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Peptide-Drug Conjugate for Therapeutic Reprogramming of Tumor-Associated Macrophages in Breast Cancer.PMC11904948PRG230CB06/01/0074PRG1788DiSCOG MARI_BIRD22_01R21-6405053838PSG38RYC2020-028754-IR21‐6405053838PID2021-122364OA-I00PRG2011Crespi-Amer MRoyo MLombardia MMarigo IScodeller PAcosta GLepland APeranzoni EAsciutto EKPeterson PTeesalu TModesti LHaljasorg UKilk KfalsePeptide-Drug Conjugate for Therapeutic Reprogramming of Tumor-Associated Macrophages in Breast Cancer.In triple-negative breast cancer (TNBC), pro-tumoral macrophages promote metastasis and suppress the immune response. To target these cells, a previously identified CD206 (mannose receptor)-binding peptide, mUNO was engineered to enhance its affinity and proteolytic stability. The new rationally designed peptide, MACTIDE, includes a trypsin inhibitor loop, from the Sunflower Trypsin Inhibitor-I. Binding studies to recombinant CD206 revealed a 15-fold lower K_D for MACTIDE compared to parental mUNO. Mass spectrometry further demonstrated a 5-fold increase in MACTIDE's half-life in tumor lysates compared to mUNO. Homing studies in TNBC-bearing mice shows that fluorescein (FAM)-MACTIDE precisely targeted CD206⁺ tumor-associated macrophages (TAM) upon intravenous, intraper2025-01-01T00:00:00Z2025 Mar2026-06-03T02:30:46.414Z2025-04-04T00:32:25.983ZS-EPMC119049483984053210.1002/advs.202410288