Chemotactic Activity of Site-Specific Multivalent Conjugates of Stromal Cell-Derived Factor 1<i>α</i> on Branched Nanoparticles — Oak Academic Publishing
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Chemotactic Activity of Site-Specific Multivalent Conjugates of Stromal Cell-Derived Factor 1<i>α</i> on Branched Nanoparticles
Department of Bioengineering and Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
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Department of Bioengineering and Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
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Department of Bioengineering and Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
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Department of Bioengineering and Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
1 Department of Bioengineering and Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
2 Department of Bioengineering and Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
3 Department of Bioengineering and Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
4 Department of Bioengineering and Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Stromal cell-derived factor 1 α (SDF1 α ) is a potent chemokine for the recruitment of stem cells. A challenge is to maintain its activity and control its release. In this study, we engineered a recombinant cysteine-SDF1 α (cysSDF1 α ) protein, and performed multivalent conjugation of cysSDF1 through the maleimide functional group to two forms of branched nanoparticles: multi-arm poly (ethylene glycol) (MA-PEG) and hyaluronic acid (HA). We characterized the ch emotactic activity of the conjugates, and determined how the molecular weight (MW) of MA-PEG and HA affected the chemotactic activity. CysSDF1 α had similar efficiency to wild-type SDF1 α in cell recruitment. Multivalent conjugation of cysSDF1 α to low MW MA-PEG (~18 nm) did not significantly affect the chemotactic activity, while the conjugation of cysSDF1 α to high MW MA-PEG (~72 nm) lowered the efficiency, possibly due to the larger spacing between conjugated SDF1 α molecules. HA has a linear backbone and a high den sity of multivalent binding sites; however, the chemotactic activity of HA-linked cys-SDF1 α was much lower, which further decreased with the increase of HA MW from 200 kDa (~0.78 μm) to 700 kDa (~2.7 μm). Digestion of HA into smaller fragments using hyaluronidase partially recovered the chemotactic ac tivity of cysSDF1 α , suggesting that high MW HA might exert steric hindrance for SDF1 α binding to its receptors on cell surface and that HA could be used as a depot for SDF1 α storage and release. These results demonstrate that multivalent conjugates of SDF1 α to nanoparticles may be used to engineer SDF1 α delivery for cell recruitment and tissue regeneration.
KeywordsSDF1<i>α</i>DeliveryCell RecruitmentSite-Specific Protein LigationMultivalent Protein Conjugates
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