New p32/gC1qR Ligands for Targeted Tumor Drug Delivery

• DOI: 10.1002/cbic.201500564
• Publication Date: 2016-02-20T16:08:38Z
• Authors: Lauri Paasonen; Shweta Sharma; Gary B. Braun; Venkata Ramana Ko...; Thomas D. Y. Chung; Zhi‐Gang She; Kazuki N. Sugahara; Marjo Yliperttula; Bainan Wu; Maurizio Pellecchia; Erkki Ruoslahti; Tambet Teesalu
• Keywords: 0301 basic medicine; Aminopyridines; Bioengineering; Antineoplastic Agents; Breast Neoplasms; Ligands; high-throughput screening; Peptides, Cyclic; Cell Line; Mitochondrial Proteins; Medicinal and Biomolecular Chemistry; Mice; 03 medical and health sciences; Drug Delivery Systems; Cell Line, Tumor; Medicinal and biomolecular chemistry; Nanotechnology; cancer; Animals; Humans; Cancer; Cyclic; Tumor; Organic Chemistry; Ethylenediamines; 3. Good health; 5.1 Pharmaceuticals; Biochemistry and cell biology; Chemical Sciences; drug delivery; peptides; Nanoparticles; nanoparticles; Female; Biochemistry and Cell Biology; Development of treatments and therapeutic interventions; Peptides; Carrier Proteins; Biotechnology

AbstractCell surface p32, the target of LyP‐1 homing peptide, is upregulated in tumors and atherosclerotic plaques and has been widely used as a receptor for systemic delivery of payloads. Here, we identified an improved LyP‐1‐mimicking peptide (TT1, CKRGARSTC). We used this peptide in a fluorescence polarization‐based high‐throughput screening of a 50 000‐compound chemical library and identified a panel of compounds that bind p32 with low micromolar affinity. Among the hits identified in the screen, two compounds were shown to specifically bind to p32 in multiple assays. One of these compounds was chosen for an in vivo study. Nanoparticles surface‐functionalized with this compound specifically adhered to surfaces coated with recombinant p32 and, when injected intravenously, homed to p32‐expressing breast tumors in mice. This compound provides a lead for the development of p32‐targeted affinity ligands that circumvent some of the limitations of peptide‐based probes in guided drug delivery.