Co-self-assembly of cationic microparticles to deliver pEGFP-ZNF580 for promoting the transfection and migration of endothelial cells

Feng, Yakai; Guo, Mengyang; Li, Wen; Hao, Xiao‐Jiang; Lü, Wei; Ren, Xiang‐Kui; Shi, Changcan; Zhang, Wencheng

doi:10.2147/ijn.s107593

Cited by 13 publications

(9 citation statements)

References 49 publications

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“…Besides linear polymer carriers, star-shaped multiarm polymers have been developed and used as gene carriers. ,, In present study, PEI was grafted onto the star-shape copolymer sorbitol-PLGA-COOH with different lengths of PLGA hydrophobic chains (2, 4, 6, 8, and 10 kDa) to obtain sorbitol-PLGA- g -PEI. Then, the diblock copolymer of mPEG-PLGA was mixed with sorbitol-PLGA- g -PEI grafting copolymer to form complex micelles by self-assembly at a weight ratio of 1:3.…”

Section: Discussionmentioning

confidence: 99%

Core/Shell Gene Carriers with Different Lengths of PLGA Chains to Transfect Endothelial Cells

Duo

Wang

et al. 2017

Langmuir

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In order to improve the transfection efficiency and reduce the cytotoxicity of gene carriers, many strategies have been used to develop novel gene carriers. In this study, five complex micelles (MSP(2 k), MSP(4 k), MSP(6 k), MSP(8 k), and MSP(10 k)) were prepared from methoxy-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (mPEG-b-PLGA) and sorbitol-poly(d,l-lactide-co-glycolide)-graft-PEI (sorbitol-PLGA-g-PEI, where the designed molecular weights of PLGA chains were 2 kDa, 4 kDa, 6 kDa, 8 kDa, and 10 kDa, respectively) copolymers by a self-assembly method, and the mass ratio of mPEG-b-PLGA to sorbitol-PLGA-g-PEI was 1/3. These complex micelles and their gene complexes had appropriate sizes and zeta potentials, and pEGFP-ZNF580 (pDNA) could be efficiently internalized into EA.hy926 cells by their gene complexes (MSP(2 k)/pDNA, MSP(4 k)/pDNA, MSP(6 k)/pDNA, MSP(8 k)/pDNA, and MSP(10 k)/pDNA). The MTT assay results demonstrated that the gene complexes had low cytotoxicity in vitro. When the hydrophobic PLGA chain increased above 6 kDa, the gene complexes showed higher performance than that prepared from short hydrophobic chains. Moreover, the relative ZNF580 protein expression levels in MSP(6 k)/pDNA, MSP(8 k)/pDNA, and MSP(10 k)/pDNA) groups were 79.6%, 71.2%, and 73%, respectively. These gene complexes could promote the transfection of endothelial cells, while providing important information and insight for the design of new and effective gene carriers to promote the proliferation and migration of endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Core/Shell Gene Carriers with Different Lengths of PLGA Chains to Transfect Endothelial Cells

Duo

Wang

et al. 2017

Langmuir

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“…PEI-based transfection reagents have shown improved transfection efficiency albeit with some cytotoxicity depending on the cell type and type and size of cargo (siRNA, ribozymes, oligonucleotides, plasmid DNA) [ 85 , 86 ]. PEIs have been used as a non-viral gene delivery system in vascular cells extensively [ 87 , 88 , 89 , 90 , 91 , 92 ]. Various architectures and formulations of PEI strongly impact the physical-chemical properties of PEI/NA complexes and transfection effectiveness in vitro [ 86 ].…”

Section: Gene‑delivery Approaches and Gene Therapymentioning

confidence: 99%

Genetic Delivery and Gene Therapy in Pulmonary Hypertension

Rai

Shihan

Seeger

et al. 2021

IJMS

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Pulmonary hypertension (PH) is a progressive complex fatal disease of multiple etiologies. Hyperproliferation and resistance to apoptosis of vascular cells of intimal, medial, and adventitial layers of pulmonary vessels trigger excessive pulmonary vascular remodeling and vasoconstriction in the course of pulmonary arterial hypertension (PAH), a subgroup of PH. Multiple gene mutation/s or dysregulated gene expression contribute to the pathogenesis of PAH by endorsing the proliferation and promoting the resistance to apoptosis of pulmonary vascular cells. Given the vital role of these cells in PAH progression, the development of safe and efficient-gene therapeutic approaches that lead to restoration or down-regulation of gene expression, generally involved in the etiology of the disease is the need of the hour. Currently, none of the FDA-approved drugs provides a cure against PH, hence innovative tools may offer a novel treatment paradigm for this progressive and lethal disorder by silencing pathological genes, expressing therapeutic proteins, or through gene-editing applications. Here, we review the effectiveness and limitations of the presently available gene therapy approaches for PH. We provide a brief survey of commonly existing and currently applicable gene transfer methods for pulmonary vascular cells in vitro and describe some more recent developments for gene delivery existing in the field of PH in vivo.

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“…To obtain high transfection efficiency and good treatment effect, different gene carriers based on cationic polymers have been prepared because of their specific characteristics, such as multifunctionality for convenient modification and intelligent design, and their convertible surface properties by altering the ratio of polymers and DNA. − Moreover, amphiphilic copolymers are one of the most widely developed carriers due to their stability, high cellular uptake, and endosome escape. − Kataoka et al prepared amphiphilic catiomer of poly(ethylene glycol)- b -poly{N′-[N-(2-aminoethyl)-2-aminoehtyl] aspartamide}-cholesteryl and developed a strategy of cyclic (Arg-Gly-Asp) (cRGD) peptide ligand conjugation at the α-terminus for specific affinity to the targeted cells. Their results showed that the cRGD conjugated carriers achieved potent tumor growth suppression by efficient gene expression of antiangiogenic protein (sFlt-1) at the tumor site in an intractable pancreatic cancer mice model .…”

Section: Introductionmentioning

confidence: 99%

“…In our previous studies, polyethylenimine (PEI) was grafted onto hydrophobic biodegradable polymers as gene carriers for EC transfection. ,− These amphiphilic copolymers with different biodegradable hydrophobic and hydrophilic segments exhibited low cytotoxicity and high gene delivery efficiency. REDV and CAG peptides were immobilized on gene carriers to improve the efficiency of gene delivery and the vascularization ability via selective adhesion to the targeted ECs relative to smooth muscle cells (SMCs).…”

Section: Introductionmentioning

confidence: 99%

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

Hao

Wang

et al. 2018

ACS Biomater. Sci. Eng.

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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.

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Co-self-assembly of cationic microparticles to deliver pEGFP-ZNF580 for promoting the transfection and migration of endothelial cells

Cited by 13 publications

References 49 publications

Core/Shell Gene Carriers with Different Lengths of PLGA Chains to Transfect Endothelial Cells

Core/Shell Gene Carriers with Different Lengths of PLGA Chains to Transfect Endothelial Cells

Genetic Delivery and Gene Therapy in Pulmonary Hypertension

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

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