Reducible chimeric polypeptide consisting of octa-d-arginine and tetra-l-histidine peptides as an efficient gene delivery vector

Wang, Xiaoyu; Tai, Zongguang; Tian, Jing; Zhang, Wei; Yan, Chong; Zhang, Lijuan; Gao, Yuan; Gao, Jing; Gao, Shaopeng

doi:10.2147/ijn.s83507

Cited by 8 publications

(3 citation statements)

References 34 publications

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“…The Smad7 gene needs the help of a gene vector with high biocompatibility and good targeting property to enter into the cells. Exosomes are small vesicles with a diameter of 30-150 nm naturally secreted by cells [ 33 ], and they can be used as potential carriers to deliver drugs, therapeutic genes or proteins in clinical treatment due to their stability and high biocompatibility [ 34 – 37 ]. In current study, the exosomes produced from mouse aortic endothelial cells were selected as vehicles of gene therapy as it mirror the marker molecules of parent cells and was associated with many physiological progresses such as anti-inflammation, anti-oxidation and the inhibition of endothelial-to-mesenchymal transition (EndMT) [ 12 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

Wei

Yang

Hsu

et al. 2021

BMC Musculoskelet Disord

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Background Heterotopic ossification (HO) can limit joint activity, causes ankylosis and impairs the function and rehabilitation of patients. Endothelial to mesenchymal transition (EndMT) plays an important role in the pathogenesis of HO, and high expression of SMAD7(Mothers Against Decapentaplegic Homolog 7) in endothelial cells can effectively reverse the TGF-β1 mediated EndMT. This article studied an appropriately engineered exosome with high biocompatibility and good targeting property to administrate SMAD7 gene therapy to inhibit the EndMT. Methods Exosomes from mouse aortic endothelial cells were cultured and harvested. DSPE-PEG and antibody CD34 were combined to exosomes to synthesize the endothelial cell targeting exosome vector (Exosome-DSPE-PEG-AbCD34). The biocompatibility, stability, targeting and cell internalization of exosome vector were tested, then the Exosome-DSPE-PEG-AbCD34 was loaded with Smad7 plasmid and administrated to MAECs to examine its therapeutic effect on EndMT of MAEC mediated by TGF-β1. Results The Exosome-DSPE-PEG-AbCD34 has no impact on MAEC cell viability at high concentration, and exosome-DSPE-PEG-AbCD34 could be stably stored at 4°C and 37°C for at least 8 days. Exosome-DSPE-PEG-AbCD34 has better targeting property to MAEC cells and can enter into the cells more effectively. The Exosome-DSPE-PEG-AbCD34-Smad7 could significantly increase the level of SMAD7, decrease the expression of TGF-β1, and effectively reverse the EndMT of MAEC mediated by TGF- β1 in MAEC cells. Conclusions The synthesized Exosome-DSPE-PEG-AbCD34-Smad7 has good biological properties and can effectively reverse the EndMT of MAEC mediated by TGF-β1. Thus, Exosome-DSPE-PEG-AbCD34-Smad7 may has the potential for the prevention and treatment of HO.

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Section: Discussionmentioning

confidence: 99%

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

Wei

Yang

Hsu

et al. 2021

BMC Musculoskelet Disord

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“…TRAIL delivered by reducible chimeric polypeptides considerably inhibited tumour growth formation in mice xenografted with HeLa cells [ 83 ].…”

Section: Trail Gene Delivery Systemmentioning

confidence: 99%

Role of nanotechnology and gene delivery systems in TRAIL based therapies

Naoum¹,

Tawadros²,

Farooqı³

et al. 2016

ecancer

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Since its identification as a member of the tumour necrosis factor (TNF) family, TRAIL (TNF-related apoptosis-inducing ligand) has emerged as a new avenue in apoptosis-inducing cancer therapies. Its ability to circumvent the chemoresistance of conventional therapeutics and to interact with cancer stem cells (CSCs) self-renewal pathways, amplified its potential as a cancer apoptotic agent. Many recombinant preparations of this death ligand and monoclonal antibodies targeting its death receptors have been tested in monotherapy and combinational clinical trials. Gene therapy is a new approach for cancer treatment which implies viral or non-viral functional transgene induction of apoptosis in cancer cells or repair of the underlying genetic abnormality on a molecular level. The role of this approach in overcoming the traditional barriers of radiation and chemotherapeutics systemic toxicity, risk of recurrence, and metastasis made it a promising platform for cancer treatment. The recent first Food Drug Administration (FDA) approved oncolytic herpes virus for melanoma treatment brings forth the potency of the cancer gene therapy approach in the future. Many gene delivery systems have been studied for intratumoural TRAIL gene delivery alone or in combination with chemotherapeutic agents to produce synergistic cancer cytotoxicity. However, there still remain many obstacles to be conquered for this different gene delivery systems. Nanomedicine on the other hand offers a new frontier for clinical trials and biomedical research. The FDA approved nanodrugs motivates horizon exploration for other nanoscale designed particles’ implications in gene delivery. In this review we aim to highlight the molecular role of TRAIL in apoptosis and interaction with cancer stem cells (CSCs) self-renewal pathways. Finally, we also aim to discuss the different roles of gene delivery systems, mesenchymal cells, and nanotechnology designs in TRAIL gene delivery.

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“…34,35 Disulfides-containing polymers are rapidly degraded under the stimulation of tumor cells and are stable in the extracellular environment. 34,36,37 Selenium, a necessary nutrient, has great potential value in biomaterials due to its high sensitivity for GSH and H 2 O 2 . 28,[38][39][40] The similarity between selenium and sulfur is manifested in atomic size, electronegativity and accessible oxidation state.…”

Section: Introductionmentioning

confidence: 99%

<p>Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression</p>

Fang

Lin

Jin

et al. 2020

IJN

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Background PEI is currently the most used non-viral gene carrier and the transfection efficiency is closely related to the molecular weight; however, the prominent problem is that the cytotoxicity increased with the molecular weight. Methods A novel redox responsive biodegradable diselenide cross-linked polymer (dPSP) was designed to enhance gene expression. ICG-pEGFP-TRAIL/dPSP nanoparticles with high drug loading are prepared, which have redox sensitivity and plasmid protection. The transfection efficiency of dPSP nanoparticle was evaluated in vitro. Results The plasmid was compressed by 100% at the N/P ratio of 16, and the particle size was less than 100 nm. When explored onto high concentrations of GSH/H 2 O 2 , dPSP4 degraded into small molecular weight cationic substances with low cytotoxicity rapidly. Singlet oxygen ( 1 O 2 ) was produced when indocyanine green (ICG) was irradiated by near-infrared laser irradiation (NIR) to promote oxidative degradation of dPSP4 nanoparticles. Under the stimulation of NIR 808 and redox agent, the particle size and PDI of ICG-pDNA/dPSP nanoparticle increased significantly. Conclusion Compared with gene therapy alone, co-transportation of dPSP4 nanoparticle with ICG and pEGFP-TRAIL had better antitumor effect. Diselenide-crosslinked polyspermine had a promising prospect on gene delivery and preparation of multifunctional anti-tumor carrier.

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Reducible chimeric polypeptide consisting of octa-d-arginine and tetra-l-histidine peptides as an efficient gene delivery vector

Cited by 8 publications

References 34 publications

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

Role of nanotechnology and gene delivery systems in TRAIL based therapies

<p>Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression</p>

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