TITLE:
Chemotactic Activity of Site-Specific Multivalent Conjugates of Stromal Cell-Derived Factor 1α on Branched Nanoparticles
AUTHORS:
Yu-Fang Hsieh, Fang Huang, Shyam Patel, Song Li
KEYWORDS:
SDF1α Delivery, Cell Recruitment, Site-Specific Protein Ligation, Multivalent Protein Conjugates
JOURNAL NAME:
Journal of Biomaterials and Nanobiotechnology,
Vol.9 No.1,
January
11,
2018
ABSTRACT: Stromal cell-derived factor 1α (SDF1α) 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-SDF1α (cysSDF1α) 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 chemotactic
activity of the conjugates, and determined how the molecular weight (MW) of
MA-PEG and HA affected the chemotactic activity. CysSDF1α had similar efficiency to wild-type SDF1α in cell recruitment. Multivalent conjugation of cysSDF1α to low MW MA-PEG (~18 nm) did not
significantly affect the chemotactic activity, while the conjugation of cysSDF1α to high MW MA-PEG (~72 nm) lowered the
efficiency, possibly due to the larger spacing between conjugated SDF1α molecules. HA has a linear backbone and a high density of multivalent binding sites; however, the
chemotactic activity of HA-linked cys-SDF1α 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 activity of cysSDF1α, suggesting that high
MW HA might exert steric hindrance for SDF1α binding to its receptors on cell surface and that
HA could be used as a depot for SDF1α storage and release. These results
demonstrate that multivalent conjugates of SDF1α to nanoparticles may be used to engineer SDF1α delivery for
cell recruitment and tissue regeneration.