Multifunctional Peptide-Based Biohybrid for Targeted Reduction of Metastatic Breast Carcinoma-Associated Osteolysis
Source abstract
Abstract
Metastatic breast carcinoma (BC) cells are prone to spreading in the bone microenvironment, leading to a vicious cycle between local osteoclast-mediated osteolysis and tumor progression. Therefore, the targeted pharmacological down-modulation of BC cell proliferation as well as osteoclast differentiation and hyperactivity might represent a promising treatment option. We developed a multifunctional peptide nanocarrier combining bioactive EPI-X4 peptides and the Rho-inhibiting C3bot enzyme from Clostridium botulinum. C3bot is preferentially internalized into the cytosol of monocytic cells, including osteoclasts, where it inhibits Rho-mediated signal transduction. However, Rho-mediated cellular processes like migration and cell division can also be inhibited in non-monocytic cells if C3bot is delivered into their cytosol by a nanocarrier. To accomplish this, we designed a supramolecular transporter where one molecule of biotinylated C3bot and three biotinylated entities of the human EPI-X4 peptide-derived CXCR4 antagonist JM173 are assembled on avidin as a central platform. This modular transport system (JM173)3-Avi-C3 down-modulated osteoclast formation and hyperactivity and delivered the therapeutic cargo C3bot successfully into the cytosol of breast cancer cells, where it inhibited Rho.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Bone Metabolism and Diseases · Bone health and treatments · Supramolecular Self-Assembly in Materials
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, University of Ulm Medical Center, Albert-Einstein-Allee 11, 89081 Ulm, Germany
Max-Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research, Ulm University Medical Center, Helmholtzstraße 14, 89081 Ulm, Germany
Institute of Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
Funding
German Research Foundation (DFG) CRC 1279 · CRC 1149
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