Polyvinylamine with moderate binding affinity as a highly effective vehicle for RNA delivery

Zhao, Yipu; Chen, Yin; Tan, Shenxing; Wang, Xue; Yang, Chaofei; Zhang, Tuo-Di; Zhang, Xi; Ye, Fei; Xu, Jing; Wu, Xuesong; Ding, Li; Zhang, Jie; Pei, Jiawei; Wang, Xueting; Zhang, Rui Xue; Xu, Jianrong; Wang, Weisi; Filipe, Carlos D. M.; Hoare, Todd; Yin, Da‐Chuan; Qian, Airong; Deng, Xudong

doi:10.1016/j.jconrel.2022.03.003

Cited by 26 publications

(22 citation statements)

References 62 publications

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“…For instance, polyethylene glycol (PEG)-grafted PEI formulation condensing mRNA shows remarkable transgene expression levels in pulmonary immune cells following systemic administration [54], and chemically modified PEI with chondrocyteaffinity peptides [55] or cyclodextrin-PEI conjugates [56] have been demonstrated to be potent and feasible gene carriers in vivo. Hence, PEI still continues to be considered the "gold standard" in non-viral gene therapy drug delivery, owing to its good transfection efficiency, which may be further improved through functionalization with a wide diversity of biomolecules/compounds [57,58], and the high interest of PEI as a non-viral vector in the transient gene expression of mammalian cells in vitro and in vivo is reflected in numerous research studies reported in the literature, some of them being under different phases of clinical investigation (Table 2). However, to address the concerns of efficiency and toxicity associated with PEI and PLL, other polymers have been preclinically investigated as gene therapy drug delivery carriers, including poly(β-amino ester)s (PBAE) and various dendrimers (Figure 1).…”

Section: Opportunitiesmentioning

confidence: 99%

Electrospun-Fibrous-Architecture-Mediated Non-Viral Gene Therapy Drug Delivery in Regenerative Medicine

2022

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Gene-based therapy represents the latest advancement in medical biotechnology. The principle behind this innovative approach is to introduce genetic material into specific cells and tissues to stimulate or inhibit key signaling pathways. Although enormous progress has been achieved in the field of gene-based therapy, challenges connected to some physiological impediments (e.g., low stability or the inability to pass the cell membrane and to transport to the desired intracellular compartments) still obstruct the exploitation of its full potential in clinical practices. The integration of gene delivery technologies with electrospun fibrous architectures represents a potent strategy that may tackle the problems of stability and local gene delivery, being capable to promote a controlled and proficient release and expression of therapeutic genes in the targeted cells, improving the therapeutic outcomes. This review aims to outline the impact of electrospun-fibrous-architecture-mediated gene therapy drug delivery, and it emphatically discusses the latest advancements in their formulation and the therapeutic outcomes of these systems in different fields of regenerative medicine, along with the main challenges faced towards the translation of promising academic results into tangible products with clinical application.

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Section: Opportunitiesmentioning

confidence: 99%

Electrospun-Fibrous-Architecture-Mediated Non-Viral Gene Therapy Drug Delivery in Regenerative Medicine

2022

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“…This proton sponge property results in an influx of negative ions into the vesicle, leading to an increase in vesicle osmotic pressure, which eventually leads to membrane rupture and the release of RNA into the cytoplasm, successfully achieving endosomal escape [ 55 , 56 ]. Among cationic polymers, PEI as a commonly used synthetic polymer gene carrier has been proven to be an effective transfection agent for delivering RNA to a variety of normal, tumor, or stem cells to facilitate in vitro and in vivo RNA delivery and gene therapy [ 57 , 58 , 59 , 60 ]. Polyethyleneimine, as a well-known polymer, mainly has two forms: linear chain and branched chain.…”

Section: Classification Of Rna Drug Carriermentioning

confidence: 99%

Broadening the Horizons of RNA Delivery Strategies in Cancer Therapy

Liu

Bai

et al. 2022

Bioengineering

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RNA-based therapy is a promising and innovative strategy for cancer treatment. However, poor stability, immunogenicity, low cellular uptake rate, and difficulty in endosomal escape are considered the major obstacles in the cancer therapy process, severely limiting the development of clinical translation and application. For efficient and safe transport of RNA into cancer cells, it usually needs to be packaged in appropriate carriers so that it can be taken up by the target cells and then be released to the specific location to perform its function. In this review, we will focus on up-to-date insights of the RNA-based delivery carrier and comprehensively describe its application in cancer therapy. We briefly discuss delivery obstacles in RNA-mediated cancer therapy and summarize the advantages and disadvantages of different carriers (cationic polymers, inorganic nanoparticles, lipids, etc.). In addition, we further summarize and discuss the current RNA therapeutic strategies approved for clinical use. A comprehensive overview of various carriers and emerging delivery strategies for RNA delivery, as well as the current status of clinical applications and practice of RNA medicines are classified and integrated to inspire fresh ideas and breakthroughs.

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“…Recently, Tian et al have demonstrated that both the transfection efficiency and cytotoxicity of PVAm are more favorable compared to those of polyethylenimine (PEI), the "gold standard" for polymerbased carriers. 11 The designed novel stimuli-responsive block copolymer (PAA-b-PVAm) may be a nontoxic carrier candidate for next-generation cancer therapy or RNA delivery. Furthermore, following decoration with Ag NPs (AgNPs@ PAA-b-PVAm), the bare and NP-containing copolymers were examined for their potential in bacterial signal molecule inhibition against a model strain, Chromobacterium violaceum, and their cytotoxicity in L929 fibroblast as a control group and MCF-7 breast cancer cell lines.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Thus, the widespread use of this superior polymer dates back to the 2000s after the commercialization of N -vinylformamide (NVF), a precursor monomer to obtain PVAm by hydrolysis . Recently, PVAm has been of great interest as a cationic polymer delivery vehicle, particularly due to the aptitude of drug molecules, oligomers, or nucleic acids to conjugate to the primary amines, greatly increasing the application space. − Herein, we incorporated a precursor PNVF block into PAA structure by chain extension, which was then reduced to give a PVAm block, that is, to yield the PAA- b -PVAm DHBC structure.…”

Section: Introductionmentioning

confidence: 99%

“…Apart from the stimuli-responsive feature that the PAA block offers to the structure, the PVAm block is a certain candidate to be an efficient delivery vehicle. Recently, Tian et al have demonstrated that both the transfection efficiency and cytotoxicity of PVAm are more favorable compared to those of polyethylenimine (PEI), the “gold standard” for polymer-based carriers . The designed novel stimuli-responsive block copolymer (PAA- b -PVAm) may be a nontoxic carrier candidate for next-generation cancer therapy or RNA delivery.…”

Section: Introductionmentioning

confidence: 99%

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Poly(acrylic acid)-b-Poly(vinylamine) Copolymer: Decoration with Silver Nanoparticles, Antibacterial Properties, Quorum Sensing Activity, and Cytotoxicity on Breast Cancer and Fibroblast Cell Lines

Ghaffarlou

Sütekin

Hammamchi

et al. 2022

ACS Appl. Polym. Mater.

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An elegant integration of primary amine-bearing segments into the acrylic acid-containing blocks and the subsequent addition of silver nanoparticles (Ag NPs) to this double hydrophilic block copolymer endowed the resulting well-defined self-assembled construct with promising antimicrobial and anti-quorum-sensing activity and high cytotoxicity against breast cancer cells. Poly(N-vinylformamide) (PNVF), precursor of amphoteric poly(vinyl amine) (PVAm), was chain-extended from pH-responsive poly(acrylic acid) (PAA) macro-chain-transfer agent synthesized via reversible addition–fragmentation chain transfer polymerization by the interchange of xanthates (RAFT/MADIX). PAA-b-PNVF block copolymers with molecular weights in the range of 12500–21800 Da and dispersities between 1.29 and 1.44 were characterized by FTIR, elemental analysis, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, and size exclusion chromatography (SEC). PAA-b-PVAm copolymer was obtained by hydrolysis of the PNVF block. The decoration of PAA-b-PVAm with monodisperse Ag NPs to yield AgNPs@PAA-b-PVAm proceeded through a simple and green approach by amine-induced reduction of Ag ions in aqueous media. The formation of AgNPs@PAA-b-PVAm was characterized by UV/vis spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM). AgNPs@PAA-b-PVAm displayed superior antimicrobial and anti-QS activity. The cell proliferation was tested with an MTT assay on L929 and MCF-7 cell lines. Both the AgNP-decorated and the bare copolymer showed significantly higher cytotoxicity on cancer cells compared to healthy ones.

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Polyvinylamine with moderate binding affinity as a highly effective vehicle for RNA delivery

Cited by 26 publications

References 62 publications

Electrospun-Fibrous-Architecture-Mediated Non-Viral Gene Therapy Drug Delivery in Regenerative Medicine

Electrospun-Fibrous-Architecture-Mediated Non-Viral Gene Therapy Drug Delivery in Regenerative Medicine

Broadening the Horizons of RNA Delivery Strategies in Cancer Therapy

Poly(acrylic acid)-b-Poly(vinylamine) Copolymer: Decoration with Silver Nanoparticles, Antibacterial Properties, Quorum Sensing Activity, and Cytotoxicity on Breast Cancer and Fibroblast Cell Lines

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