CAGW Modified Polymeric Micelles with Different Hydrophobic Cores for Efficient Gene Delivery and Capillary-like Tube Formation

Abstract

Recently, polymeric micelles with different biodegradable hydrophobic cores, such as poly­(lactide-co-glycolide) (PLGA) and poly­(lactide-co-3­(S)-methyl-morpholine-2,5-dione) (PLMD), have been used for gene delivery. The biodegradable hydrophobic cores should play an important role in gene delivery. However, little research has focused on selectively promoting proliferation and migration of endothelial cells (ECs) as well as vascularization by altering hydrophobic cores of polymeric micelles. Herein, we prepared two kinds of CAGW peptide (selective adhesion for ECs) modified micelles with PLGA and PLMD as hydrophobic cores, respectively, and poly­(ethylene glycol) (PEG) and polyethylenimine (PEI) as mixed hydrophilic shell. Their ability of condensing pEGFP-ZNF580 (pZNF580) to form gene complexes was proved by agarose gel electrophoresis assay. MTT results showed that the relative cell viability of the micelles with PLMD cores was higher than control groups and the micelles with PLGA cores. The cellular uptake ability of these CAGW modified gene complexes was higher than the complexes without CAGW target function. A similar trend was also found in transfection tests in vitro, which further demonstrated the effect of CAGW peptide and different hydrophobic cores on gene delivery. The number of migrated cells treated by the gene complexes with PLGA cores was 82 (nontarget group) and 115 (target group), whereas the complexes with PLMD cores was 88 (nontarget group) and 120 (target group). Capillary-like tube formation of CAGW peptide modified complexes with PLMD core group was much higher (about 6 times) than the PEI­(10 kDa)/pZNF580 group. These results demonstrated that transfection efficiency, cell proliferation, migration, and vascularization could be promoted by altering hydrophobic cores and CAGW modification.

Composite Tissue Adhesive Containing Catechol-Modified Hyaluronic Acid and Poly-l-lysine

“…The tube numbers of the CLSs formed on the hydrogels obtained from 0.1% PLL/2% HACA0.47 or 0.05% PLL/2% HACA0.47 were both ∼15 per field, which was similar to those previously reported with a mean tube number between 10 and 15 per observation field. 48 The results above indicate that PLL significantly improves cell adhesion and CLS formation on HACA as tested using HUV-EC-Cs as a model cell line. The formation of blood vessels is important to sustain cell metabolism at the sites of wounds or implants by providing oxygen and nutrients.…”

“…As shown in Figure 6B, the cells formed CLSs with a mean tube length of ∼130 μm on the hydrogels obtained from 0.1% PLL/2% HACA0.47, which was similar to those observed on Matrigel and HA-gelatin hydrogel. 48,49 However, the tube length of the CLSs on the hydrogels obtained from 0.05% PLL/2% HACA0.47 was only ∼74 μm (Figure 6C). The tube numbers of the CLSs formed on the hydrogels obtained from 0.1% PLL/2% HACA0.47 or 0.05% PLL/2% HACA0.47 were both ∼15 per field, which was similar to those previously reported with a mean tube number between 10 and 15 per observation field.…”

Phenylboronic ester-modified anionic micelles for ROS-stimuli response in HeLa cell

“…Each experiment was repeated three times in sextuplicate. The cell viability was calculated according to following formula (Hao et al, 2018):…”

Bioreducible cationic random copolymer for gene delivery

“…Various studies have proved the advantages and potential application of pZNF580 in the transfection of ECs 17,23 . Different cationic polymers have been used to carry pZNF580 to ECs 16,21,23‐31 . These cationic polymers can form positive charge complexes (polyplexes) with DNA due to the electrostatic interaction between the positively charged polymers and negatively charged DNA.…”