Depletion of CD206+ Tumour Macrophages via a Peptide-Targeted Star-Shaped Polyglutamate Inhibits Tumourigenesis and Metastatic Dissemination in Breast Cancer Models
Lepland, A.; Malfanti, A.; Haljasorg, U.; Asciutto, E.; Pickholz, M.; Bringas, M.; Dordevic, S.; Salumae, L.; Peterson, P.; Teesalu, T.; Vicent, M. J.; Scodeller, P.
Show abstract
Although many studies have explored the depletion of tumour-associated macrophages (TAMs) as a therapeutic strategy for solid tumours, currently available compounds suffer from poor efficacy and dose-limiting side effects. Here, we developed a novel TAM-depleting agent ("OximUNO") that specifically targets CD206+ TAMs and demonstrated efficacy in triple negative breast cancer (TNBC) mouse models. OximUNO comprises a star-shaped polyglutamate (St-PGA) decorated with the CD206-targeting peptide mUNO that carries the chemotherapeutic drug doxorubicin (DOX). In TNBC models, a fluorescently labelled mUNO-decorated St-PGA homed to CD206+ TAMs within primary lesions and metastases. OximUNO exhibited no acute liver or kidney toxicity in vivo. Treatment with OximUNO reduced the progression of primary tumour lesions and pulmonary metastases, significantly diminished the number of CD206+ TAMs and increased the CD8/FOXP3 expression ratio (demonstrating immunostimulation). Our findings suggest the potential benefit of OximUNO as a TAM-depleting agent for TNBC treatment. Importantly, our studies also represent the first report of a peptide-targeted St-PGA as a targeted therapeutic nanoconjugate.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance 96%
- Cycling Molecular Assemblies for Selective Cancer Cell Golgi Disruption 95%
- Ligand supplementation restores the cancer therapy efficacy of an antirheumatic drug auranofin from serum inactivation 95%
Similar papers in this journal
- Immunofilaments Provide a Nanoscale Platform for In Vivo T Cell Expansion and Cancer Immunotherapy 96%
- SARS-CoV-2 B Epitope-Guided Neoantigen NanoVaccines Enhance Tumor-Specific CD4/CD8 T Cell Immunity Through B Cell Antigen Presentation 95%
- Marginated neutrophils in the lungs effectively compete for nanoparticles targeted to the endothelium, serving as a part of the reticuloendothelial system 95%
Similar papers in this journal
- Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI3k delta inhibitor enhances therapeutic benefits of radiotherapy 95%
- Natural killer cell-mimic nanoparticles can actively target and kill acute myeloid leukemia cells 95%
- A synthetic delivery vector for mucosal vaccination 94%
Similar papers in this journal
- {Pi}-{Pi} Interactions Stabilize PeptoMicelle-Based Formulations of Pretomanid Derivatives Leading to Promising Therapy Against Tuberculosis in Zebrafish and Mouse Models 95%
- TLR7 and RIG-I dual-adjuvant loaded nanoparticles drive broadened and synergistic responses in dendritic cells in vitro and generate unique cellular immune responses in influenza vaccination 95%
- Targeting Langerhans cells using a modular mannosylated nucleic acid-based vaccine platform 95%
Similar papers in this journal
- Physicochemical Targeting of Lipid Nanoparticles to the Lungs Induces Clotting: Mechanisms and Solutions 95%
- Truly tiny acoustic biomolecules for ultrasound imaging and therapy 94%
- Hydrogel-based slow release of a receptor-binding domain subunit vaccine elicits neutralizing antibody responses against SARS-CoV-2 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.