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CXCL5 Modified Nanoparticle Surface Improves CXCR2+ Cell Selective Internalization.

ABSTRACT: Driving nanomaterials to specific cell populations is still a major challenge for different biomedical applications. Several strategies to improve cell binding and uptake have been tried thus far by intrinsic material modifications or decoration with active molecules onto their surface. In the present work, we covalently bound the chemokine CXCL5 on fluorescently labeled amino-functionalized SiO2 nanoparticles to precisely targeting CXCR2+ immune cells. We synthesized and precisely characterized the physicochemical features of the modified particles. The presence of CXCL5 on the surface was detected by z-potential variation and CXCL5-specific electron microscopy immunogold labeling. CXCL5-amino SiO2 nanoparticle cell binding and internalization performances were analyzed in CXCR2+ THP-1 cells by flow cytometry and confocal microscopy. We showed improved internalization of the chemokine modified particles in the absence or the presence of serum. This internalization was reduced by cell pre-treatment with free CXCL5. Furthermore, we demonstrated CXCR2+ cell preferential targeting by comparing particle uptake in THP-1 vs. low-CXCR2 expressing HeLa cells. Our results provide the proof of principle that chemokine decorated nanomaterials enhance uptake and allow precise cell subset localization. The possibility to aim at selective chemokine receptor-expressing cells can be beneficial for the diverse pathological conditions involving immune reactions.

SUBMITTER: Cagliani R

PROVIDER: S-EPMC7016632 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Project description:BackgroundAdvances in Molecular Therapy have made gene editing through systemic or topical administration of reagents a feasible strategy to treat genetic diseases in a rational manner. Encapsulation of therapeutic agents in nanoparticles can improve intracellular delivery of therapeutic agents, provided that the nanoparticles are efficiently taken up within the target cells. In prior work we had established proof-of-principle that nanoparticles carrying gene editing reagents can mediate site-specific gene editing in fetal and adult animals in vivo that results in functional disease improvement in rodent models of β-thalassemia and cystic fibrosis. Modification of the surface of nanoparticles to include targeting molecules (e.g. antibodies) holds the promise of improving cellular uptake and specific cellular binding.Methods and findingsTo improve particle uptake for diseases of the airway, like cystic fibrosis, our group tested the impact of nanoparticle surface modification with cell surface marker antibodies on uptake in human bronchial epithelial cells in vitro. Binding kinetics of antibodies (Podoplanin, Muc 1, Surfactant Protein C, and Intracellular Adhesion Molecule-1 (ICAM)) were determined to select appropriate antibodies for cellular targeting. The best target-specific antibody among those screened was ICAM antibody. Surface conjugation of nanoparticles with antibodies against ICAM improved cellular uptake in bronchial epithelial cells up to 24-fold.ConclusionsThis is a first demonstration of improved nanoparticle uptake in epithelial cells using conjugation of target specific antibodies. Improved binding, uptake or specificity of particles delivered systemically or to the luminal surface of the airway would potentially improve efficacy, reduce the necessary dose and thus safety of administered therapeutic agents. Incremental improvement in the efficacy and safety of particle-based therapeutic strategies may allow genetic diseases such as cystic fibrosis to be cured on a fundamental genetic level before birth or shortly after birth.

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CXCL5 Modified Nanoparticle Surface Improves CXCR2+ Cell Selective Internalization.

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