1 research outputs found
Multitargeting Peptide-Functionalized Star-Shaped Copolymers with Comblike Structure and a POSS-Core To Effectively Transfect Endothelial Cells
Gene
therapy meets one serious bottleneck in clinical application,
namely, lack of safe and efficient gene delivery systems. In order
to solve this problem, we designed a lowly cytotoxic and highly efficient
gene delivery system for the transfection of endothelial cells. Octa(3-ammoniumpropyl)octasilsesquioxane
octachloride reacted with 2-bromoisobutyryl bromide under alkaline
condition, and sequentially initiated 2-(dimethylamino)ethyl methacrylate
(DMAEMA) and poly(ethylene glycol) monomethacrylate (PEGMA) via atom
transfer radical polymerization (ATRP) to prepare the eight-arm copolymer
with a biocompatible polyhedral oligomericsilsesquioxane (POSS). The
side chain ends of the comblike PPEGMA were double-bonded to facilitate
the attachment of CAGW or CAG-TAT-NLS functional peptide, thereby
enabling the star-shaped copolymers with multifunction. The peptide-functionalized
star-shaped copolymers were self-assembled into nanoparticles (NPs)
and used to condense pEGFP-ZNF580 (pDNA) to prepare the NPs/pDNA complexes.
These complexes had low toxicity as confirmed by MTT. The results
of fluorescence microscopy and flow cytometry showed that these multitargeting
functionalized gene complexes could effectively transfect endothelial
cells. Their transfection efficiency is higher than the positive control
PEI 25 kDa group. Moreover, the Western blot test, wound healing assay,
and in vitro tube formation assay also demonstrated that the transfected
cells showed high migration and enhanced angiogenesis. The pDNA was
effective delivered and expressed in endothelial cells by these multitargeting
functionalized gene complexes, and promoted cell migration and tube
formation. These star-shaped copolymers with comblike structure and
a POSS core are a potential gene carrier for gene therapy