CXCL12-PLGA/Pluronic Nanoparticle Internalization Abrogates CXCR4-Mediated Cell Migration.
Anissa PisaniRoberto DonnoArianna GennariGiulia CibecchiniFederico CatalanoRoberto MarottaPier Paolo PompaNicola TirelliGiuseppe BardiPublished in: Nanomaterials (Basel, Switzerland) (2020)
Chemokine-induced chemotaxis mediates physiological and pathological immune cell trafficking, as well as several processes involving cell migration. Among them, the role of CXCL12/CXCR4 signaling in cancer and metastasis is well known, and CXCR4 has been often targeted with small molecule-antagonists or short CXCL12-derived peptides to limit the pathological processes of cell migration and invasion. To reduce CXCR4-mediated chemotaxis, we adopted a different approach. We manufactured poly(lactic acid-co-glycolic acid) (PLGA)/Pluronic F127 nanoparticles through microfluidics-assisted nanoprecipitation and functionalized them with streptavidin to docking a biotinylated CXCL12 to be exposed on the nanoparticle surface. Our results show that CXCL12-decorated nanoparticles are non-toxic and do not induce inflammatory cytokine release in THP-1 monocytes cultured in fetal bovine and human serum-supplemented media. The cell internalization of our chemokine receptor-targeting particles increases in accordance with CXCR4 expression in FBS/medium. We demonstrated that CXCL12-decorated nanoparticles do not induce cell migration on their own, but their pre-incubation with THP-1 significantly decreases CXCR4+-cell migration, thereby antagonizing the chemotactic action of CXCL12. The use of biodegradable and immune-compatible chemokine-mimetic nanoparticles to reduce cell migration opens the way to novel antagonists with potential application in cancer treatments and inflammation.
Keyphrases
- cell migration
- small molecule
- drug delivery
- papillary thyroid
- oxidative stress
- quantum dots
- single cell
- lactic acid
- cancer therapy
- poor prognosis
- dendritic cells
- immune response
- mesenchymal stem cells
- bone marrow
- molecular dynamics simulations
- high resolution
- binding protein
- climate change
- drug induced
- childhood cancer
- reduced graphene oxide
- amino acid