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Abstract
Background
Cell-targeting peptides or proteins are appealing tools in nanomedicine and innovative medicines because they increase the local drug concentration and reduce potential side effects. CXC chemokine receptor 4 (CXCR4) is a cell surface marker associated with several severe human pathologies, including colorectal cancer, for which intracellular targeting agents are currently missing.
Results
Four different peptides that bind CXCR4 were tested for their ability to internalize a green fluorescent protein-based reporter nanoparticle into CXCR4+ cells. Among them, only the 18 mer peptide T22, an engineered segment derivative of polyphemusin II from the horseshoe crab, efficiently penetrated target cells via a rapid, receptor-specific endosomal route. This resulted in accumulation of the reporter nanoparticle in a fully fluorescent and stable form in the perinuclear region of the target cells, without toxicity either in cell culture or in an in vivo model of metastatic colorectal cancer.
Conclusion
Given the urgent demand for targeting agents in the research, diagnosis, and treatment of CXCR4-linked diseases, including colorectal cancer and human immunodeficiency virus infection, T22 appears to be a promising tag for the intracellular delivery of protein drugs, nanoparticles, and imaging agents.
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Acknowledgments
We appreciate the technical support of Fran Cortés from the Cell Culture Unit of the Servei de Cultius Cellulars, Producció d’Anticossos i Citometria, of the Servei de Microscòpia, and of the Protein Production Platform (CIBER-BBN). We also acknowledge the financial support received for the design and production of artificial viruses for gene therapy to EV, RM, and AV from FIS (PS0900165, PS0900965), MICINN (ACI2009-0919), AGAUR (2009SGR-108), and CIBER de Bioingeniería, Biomateriales y Nanomedicina, an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. UU and JDE have received predoctoral fellowships from ISCIII and MICINN, respectively, and AV has received an Institució Catalana de Recerca i Estudis Avançats Academia award.
Disclosures
UU, EV, NFM, AV, RM, IC, and MVC are cited as inventors in a patent application (EP11382005.4) covering the therapeutic use of T22. All other authors report no conflicts of interest in this work.