New Polymer of lactic-co-glycolic acid-modified Polyethylenimine for Nucleic Acid Delivery

Lü, Jian; Liang, Zhibin; Wang, Xiaoxiao; Gu, Jianhua; Yao, Qizhi; Chen, Changyi

doi:10.2217/nnm-2016-0128

Cited by 13 publications

(15 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with our findings, these studies reported improved delivery and/or decreased cytotoxicity compared to PLGA-NPs or PEI alone. [20][21][22][23] Our investigations provide further novelty with the application of arginine-modified PEI, which are not only significantly more biocompatible than unmodified PEI but also augment NP uptake and subsequent gene expression. 14,15 Thus, the arginine additions of A 5 P 10 could be a fundamental factor increasing cell entry of PLGA/pDNA-NPs during cotransfection.…”

Section: Discussionmentioning

confidence: 81%

<p>Arginine-Modified Polymers Facilitate Poly (Lactide-Co-Glycolide)-Based Nanoparticle Gene Delivery to Primary Human Astrocytes</p>

Proulx¹,

Joshi²,

Vijayaraghavalu³

et al. 2020

IJN

View full text Add to dashboard Cite

Purpose: Astrocyte dysfunction is a hallmark of central nervous system injury or infection. As a primary contributor to neurodegeneration, astrocytes are an ideal therapeutic target to combat neurodegenerative conditions. Gene therapy has arisen as an innovative technique that provides excellent prospect for disease intervention. Poly (lactide-co-glycolide) (PLGA) and polyethylenimine (PEI) are polymeric nanoparticles commonly used in gene delivery, each manifesting their own set of advantages and disadvantages. As a clinically approved polymer by the Federal Drug Administration, well characterized for its biodegradability and biocompatibility, PLGA-based nanoparticles (PLGA-NPs) are appealing for translational gene delivery systems. However, our investigations revealed PLGA-NPs were ineffective at facilitating exogenous gene expression in primary human astrocytes, despite their success in other cell lines. Furthermore, PEI polymers illustrate high delivery efficiency but induce cytotoxicity. The purpose of this study is to develop viable and biocompatible NPsystem for astrocyte-targeted gene therapy. Materials and Methods: Successful gene expression by PLGA-NPs alone or in combination with arginine-modified PEI polymers (A n P n ) was assessed by a luciferase reporter gene encapsulated in PLGA-NPs. Cytoplasmic release and nuclear localization of DNA were investigated using fluorescent confocal imaging with YOYO-labeled plasmid DNA (pDNA). NP-mediated cytotoxicity was assessed via lactate dehydrogenase in primary human astrocytes and neurons. Results: Confocal imaging of YOYO-labeled pDNA confirmed PLGA-NPs delivered pDNA to the cytoplasm in a dose and time-dependent manner. However, co-staining revealed pDNA delivered by PLGA-NPs did not localize to the nucleus. The addition of A n P n significantly improved nuclear localization of pDNA and successfully achieved gene expression in primary human astrocytes. Moreover, these formulations were biocompatible with both astrocytes and neurons. Conclusion: By co-transfecting two polymeric NPs, we developed an improved system for gene delivery and expression in primary human astrocytes. These findings provide a basis for a biocompatible and clinically translatable method to regulate astrocyte function during neurodegenerative diseases and disorders.

show abstract

Section: Discussionmentioning

confidence: 81%

<p>Arginine-Modified Polymers Facilitate Poly (Lactide-Co-Glycolide)-Based Nanoparticle Gene Delivery to Primary Human Astrocytes</p>

Proulx¹,

Joshi²,

Vijayaraghavalu³

et al. 2020

IJN

View full text Add to dashboard Cite

show abstract

“…Another study demonstrated that gold nanoparticles were attractive platforms for anti-miR-21 delivery to OvCa cells as they efficiently silenced endogenous miR-21 and disrupted cell colony formation [ 108 ]. Lactic-co-glycolic acid-modified polyethylenimine (LGA-PEI) could successfully transfer miR-520h mimics into ovarian xenograft tumors [ 150 ]. Along the same line, miR-155 loaded-PEI nanocomplexes were used for OvCa immunotherapy.…”

Section: Application Of Mirna-based Therapeutics In Selected Cancersmentioning

confidence: 99%

MicroRNA Therapeutics in Cancer: Current Advances and Challenges

Sayed

Cristante

Guyon

et al. 2021

Cancers

110

View full text Add to dashboard Cite

The discovery of microRNAs (miRNAs) in 1993 has challenged the dogma of gene expression regulation. MiRNAs affect most of cellular processes from metabolism, through cell proliferation and differentiation, to cell death. In cancer, deregulated miRNA expression leads to tumor development and progression by promoting acquisition of cancer hallmark traits. The multi-target action of miRNAs, which enable regulation of entire signaling networks, makes them attractive tools for the development of anti-cancer therapies. Hence, supplementing downregulated miRNA by synthetic oligonucleotides or silencing overexpressed miRNAs through artificial antagonists became a common strategy in cancer research. However, the ultimate success of miRNA therapeutics will depend on solving pharmacokinetic and targeted delivery issues. The development of a number of nanocarrier-based platforms holds significant promises to enhance the cell specific controlled delivery and safety profile of miRNA-based therapies. In this review, we provide among the most comprehensive assessments to date of promising nanomedicine platforms that have been tested preclinically, pertaining to the treatment of selected solid tumors including lung, liver, breast, and glioblastoma tumors as well as endocrine malignancies. The future challenges and potential applications in clinical oncology are discussed.

show abstract

“…The utilisation of polymer-based nanoparticles for enabling the delivery of a spectrum of drugs, including miRNAs, is becoming evermore commonplace with versatile and non-immunogenic polymers such as polyethylenimine and polyethylene glycol being utilised as nanoparticle backbones [121][122][123][124][125]. Typical advantages of the use of polymers for nanoparticle drug delivery systems include a highly flexible drug release kinetic profile on response to acid exposure [93].…”

Section: Non-viral-based Delivery Systems (A) Polymer Nanoparticlesmentioning

confidence: 99%

An Analysis of Mechanisms for Cellular Uptake of miRNAs to Enhance Drug Delivery and Efficacy in Cancer Chemoresistance

Grixti

Ayers

Day

2021

ncRNA

View full text Add to dashboard Cite

Up until recently, it was believed that pharmaceutical drugs and their metabolites enter into the cell to gain access to their targets via simple diffusion across the hydrophobic lipid cellular membrane, at a rate which is based on their lipophilicity. An increasing amount of evidence indicates that the phospholipid bilayer-mediated drug diffusion is in fact negligible, and that drugs pass through cell membranes via proteinaceous membrane transporters or carriers which are normally used for the transportation of nutrients and intermediate metabolites. Drugs can be targeted to specific cells and tissues which express the relevant transporters, leading to the design of safe and efficacious treatments. Furthermore, transporter expression levels can be manipulated, systematically and in a high-throughput manner, allowing for considerable progress in determining which transporters are used by specific drugs. The ever-expanding field of miRNA therapeutics is not without its challenges, with the most notable one being the safe and effective delivery of the miRNA mimic/antagonist safely to the target cell cytoplasm for attaining the desired clinical outcome, particularly in miRNA-based cancer therapeutics, due to the poor efficiency of neo-vascular systems revolting around the tumour site, brought about by tumour-induced angiogenesis. This acquisition of resistance to several types of anticancer drugs can be as a result of an upregulation of efflux transporters expression, which eject drugs from cells, hence lowering drug efficacy, resulting in multidrug resistance. In this article, the latest available data on human microRNAs has been reviewed, together with the most recently described mechanisms for miRNA uptake in cells, for future therapeutic enhancements against cancer chemoresistance.

show abstract

New Polymer of lactic-co-glycolic acid-modified Polyethylenimine for Nucleic Acid Delivery

Cited by 13 publications

References 69 publications

<p>Arginine-Modified Polymers Facilitate Poly (Lactide-Co-Glycolide)-Based Nanoparticle Gene Delivery to Primary Human Astrocytes</p>

<p>Arginine-Modified Polymers Facilitate Poly (Lactide-Co-Glycolide)-Based Nanoparticle Gene Delivery to Primary Human Astrocytes</p>

MicroRNA Therapeutics in Cancer: Current Advances and Challenges

An Analysis of Mechanisms for Cellular Uptake of miRNAs to Enhance Drug Delivery and Efficacy in Cancer Chemoresistance

Contact Info

Product

Resources

About