Gene delivery efficiency and cytotoxicity of heterocyclic amine-modified PAMAM and PPI dendrimers

Hashemi, Maryam; Tabatabai, Seyed Meghdad; Parhiz, Hamideh; Milanizadeh, Soroush; Farzad, Sara Amel; Abnous, Khalil; Ramezani, Mohammad

doi:10.1016/j.msec.2016.01.023

Cited by 30 publications

(17 citation statements)

References 43 publications

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“…PAMAM has been extensively used in vitro due to its low cytotoxicity (Eichman et al, 2000). To increase gene transfer efficiency and biocompatibility, many functionalizations of PAMAM have been performed; these functionalizations include the substitution of positive charges with arginine groups (Choi et al, 2004), PEG (Luo and Saltzman, 2006; Wang et al, 2009), and pyridine/histidine (Hashemi et al, 2016) and the addition of hydrophobic chains, including lauroyl (Santos et al, 2010). Nevertheless, as a positively charged hydrophilic molecule, PAMAM cannot cross the BBB in vivo .…”

Section: Chemical Methods For Transfectionmentioning

confidence: 99%

In vivo methods for acute modulation of gene expression in the central nervous system

Cwetsch

Pinto

Savardi

et al. 2018

Progress in Neurobiology

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Accurate and timely expression of specific genes guarantees the healthy development and function of the brain. Indeed, variations in the correct amount or timing of gene expression lead to improper development and/or pathological conditions. Almost forty years after the first successful gene transfection in in vitro cell cultures, it is currently possible to regulate gene expression in an area-specific manner at any step of central nervous system development and in adulthood in experimental animals in vivo, even overcoming the very poor accessibility of the brain. Here, we will review the diverse approaches for acute gene transfer in vivo, highlighting their advantages and disadvantages with respect to the efficiency and specificity of transfection as well as to brain accessibility. In particular, we will present well-established chemical, physical and virus-based approaches suitable for different animal models, pointing out their current and future possible applications in basic and translational research as well as in gene therapy.

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Section: Chemical Methods For Transfectionmentioning

confidence: 99%

In vivo methods for acute modulation of gene expression in the central nervous system

Cwetsch

Pinto

Savardi

et al. 2018

Progress in Neurobiology

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“…The coupling of amino acids arginine, leucine or lysine strongly enhanced gene expression efficiencies of G3 PPI-based complexes and even of the very small G2 PPI [43,44]. Similarly, the modification of the larger G4/G5 PPIs with heterocyclic amines (histidine, piperazine-2-carboxyilic acid and 3-pyridyl acetic acid) reduced cytotoxicity, while leading to higher gene expression levels [45].…”

Section: Introductionmentioning

confidence: 99%

Tyrosine-Modification of Polypropylenimine (PPI) and Polyethylenimine (PEI) Strongly Improves Efficacy of siRNA-Mediated Gene Knockdown

et al. 2020

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The delivery of small interfering RNAs (siRNA) is an efficient method for gene silencing through the induction of RNA interference (RNAi). It critically relies, however, on efficient vehicles for siRNA formulation, for transfection in vitro as well as for their potential use in vivo. While polyethylenimines (PEIs) are among the most studied cationic polymers for nucleic acid delivery including small RNA molecules, polypropylenimines (PPIs) have been explored to a lesser extent. Previous studies have shown the benefit of the modification of small PEIs by tyrosine grafting which are featured in this paper. Additionally, we have now extended this approach towards PPIs, presenting tyrosine-modified PPIs (named PPI-Y) for the first time. In this study, we describe the marked improvement of PPI upon its tyrosine modification, leading to enhanced siRNA complexation, complex stability, siRNA delivery, knockdown efficacy and biocompatibility. Results of PPI-Y/siRNA complexes are also compared with data based on tyrosine-modified linear or branched PEIs (LPxY or PxY). Taken together, this establishes tyrosine-modified PPIs or PEIs as particularly promising polymeric systems for siRNA formulation and delivery.

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“…In order to achieve the coadministration of hydrophobic PTX and Nur77 gene, we have designed a cationic micelle nanosystem based on the amphiphilic triblock poly[(R)‐3‐hydroxybutyrate]‐poly(2‐(dimethylamino)ethyl methacrylate) (PHB‐ b ‐PDMAEMA) copolymer, as shown in Scheme 1 . Over the years, various organic and inorganic nonviral vectors have been investigated for gene delivery applications, while many researchers have further explored the drug and gene codelivery nanosystems for enhanced cancer therapy . As a typical example, Xu and co‐workers designed a series of next generation ethanolamine functionalized poly(glycidyl methacrylate) as well as their derivative cationic polymers, for enhanced stability or gene transfection efficiency as well as drug/gene codelivery .…”

Section: Introductionmentioning

confidence: 99%

Codelivery for Paclitaxel and Bcl‐2 Conversion Gene by PHB‐PDMAEMA Amphiphilic Cationic Copolymer for Effective Drug Resistant Cancer Therapy

Wang

Liow

et al. 2017

Macromolecular Bioscience

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Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydrophobic PHB segment. This copolymer shows less toxicity but similar gene transfection efficiency to polyethyenimine (25k). More importantly, this codelivery approach by PHB-PDMAEMA leads to increased drug resistant HepG2/Bcl-2 cancer cell death, by increased expression of Nur77 proteins in the Bcl-2 present intracellular mitochondria. This work signifies for the first time that cationic amphiphilic PHB-b-PDMAEMA copolymers can be utilized for the drug and gene codelivery to drug resistant cancer cells with high expression of antiapoptosis Bcl-2 protein and the positive results are encouraging for the further design of codelivery platforms for combating drug resistant cancer cells.

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Gene delivery efficiency and cytotoxicity of heterocyclic amine-modified PAMAM and PPI dendrimers

Cited by 30 publications

References 43 publications

In vivo methods for acute modulation of gene expression in the central nervous system

In vivo methods for acute modulation of gene expression in the central nervous system

Tyrosine-Modification of Polypropylenimine (PPI) and Polyethylenimine (PEI) Strongly Improves Efficacy of siRNA-Mediated Gene Knockdown

Codelivery for Paclitaxel and Bcl‐2 Conversion Gene by PHB‐PDMAEMA Amphiphilic Cationic Copolymer for Effective Drug Resistant Cancer Therapy

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