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.

CXCL12-PLGA/Pluronic Nanoparticle Internalization Abrogates CXCR4-Mediated Cell Migration

“…We cannot assert that higher CXCR4 expression is the only event increasing CXCL12-NP internalization, but it could contribute to the highest NP chemokine uptake at 2 h in the FBS medium. As already show in our previous work for a different chemokine-decorated particle [ 41 ], we confirmed CXCL12-NP/CXCR4 binding ( Figure S6 ) by inhibition of CXCL12-NP internalization. The THP-1 cells were pretreated with free CXCL12 for 45 min before performing NP internalization.…”

“…In a previous work aimed at developing NPs for specific targeting, we covalently bound an entire chemokine on the surface of SiO 2 NPs [ 41 ], whose structure and steric hindrance can limit the opsonization of other proteins. The CXCL5-SiO 2 NPs’ internalization through the CXCL5 cognate receptor (CXCR2) was increased with regard to the non-chemokine modified particles, even in the presence of serum.…”

Potential Applications of Nanomaterials to Quench the Cytokine Storm in Coronavirus Disease 19

“…Another way to antagonize the action of chemo-attractant cytokines could be obtained by the functionalization of NPs with the same chemokines covalently bound onto the particle surface (Cagliani et al, 2019b ). We synthesized CXCL5-NPs proving that these particles are highly internalized in CXCR2 + cells but not in cells expressing low levels of this receptor.…”

Suppressing MDSC Recruitment to the Tumor Microenvironment by Antagonizing CXCR2 to Enhance the Efficacy of Immunotherapy

“…In addition to these promising pre-clinical studies, CXCR2-transduced autologous tumor-infiltrating lymphocytes are under clinical investigation in patients with metastatic melanoma ( Table 1 ). Additionally, there are ongoing efforts to target CXCR2+ positive cells using CXCL5-modified nanoparticles to deliver drug [ 67 ]. Natural killer (NK) cells are another effector immune cell type that can have direct cytotoxic activities against tumor cells [ 68 ].…”