Phage display identified peptide with selectivity for human osteoarthritic chondrocytes

Osteoarthritis (OA) is one of the most common joint disorders in western populations, affecting millions of people worldwide and with a rising incidence as life expectancy continues to increase. Current therapies for OA management fail to halt the progressive degradation of articular cartilage, urging the need for more effective therapies to improve cartilage function and enhance patient's quality of life. Through phage display technology, biopanning on a population of heterogenous chondrocyte cells isolated from six different OA donors, and using a random 12-amino acid peptide phage library, a peptide selective for human OA chondrocytes (GFQMISNNVYMR) is identified. A twofold increase in fluorescence intensity is observed for OA chondrocytes, compared to normal chondrocytes, when cells are incubated with the identified peptide conjugated to a fluorescent label, being selectively internalized by OA cells. The identified peptide can be further modified and exploited for developing early diagnostic of OA and/or improve drug delivery to target cells through peptide-drug conjugates.

This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the project PTDC/EBBBIO/114523/2009 and the strategic funding of UIDB/04469/2020 unit, by the European Regional Development Fund (ERDF) through the Operational Competitiveness Programme “COMPETE” (FCOMP-01-0124- FEDER-014758). The authors thank FCT the strategic funding of UID/BIO/04469/2013 unit and RECI/BBB-EBI/0179/2012 (FCOMP-01- 0124-FEDER-027462). R.F.C. and J.M.O. are also thankful to FCT, Fundo Europeu de Desenvolvimento Regional (FEDER), and Programa Operacional Competitividade e Internacionalização (POCI) for funding the BLiver Project (PTDC/EMD-EMD/29139/2017). R.F.C. and J.M.O. thank the financial support provided under the project “HEALTH-UNORTE: Settingup biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological, and infectious diseases,” reference NORTE-01-0145-FEDER-000039, funded by the Norte Portugal Regional Coordination and Development Commission (CCDR-N), under the NORTE2020 Program. H.S.A. thanks the MOBILIsE project funded by the European Union’s Horizon 2020 research and innovation programme under Grant Agreement no. 951723.