PAMAM dendrimer roles in gene delivery methods and stem cell research

Daneshvar, Nasibeh; Abdullah, Rasedee; Shamsabadi, Fatemeh T.; How, Chee Wun; Mh, Malim; Mehrbod, Parvaneh

doi:10.1002/cbin.10051

Cited by 24 publications

(7 citation statements)

References 51 publications

(50 reference statements)

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“…34 Several modifications have been made on PAMAM to improve its physicochemical and biological properties as a gene carrier into MSCs, including using RGD peptide and hyaluronic acid. 35,36 In a recent report, PAMAM G5 was conjugated to lauric, myristic, and palmitic fatty acids to evaluate their effects on the gene delivery activity of PAMAM in MSCs. The highest efficiency was obtained by the vectors containing the smallest hydrophobic chains.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of efficient gene delivery systems by grafting pegylated alkylcarboxylate chains to PAMAM dendrimers: Evaluation of transfection efficiency and cytotoxicity in cancerous and mesenchymal stem cells

et al. 2015

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The applications of polyamidoamine (PAMAM) dendrimers have attracted much attention in biomedicine specially non-viral gene delivery because of thier unique characteristics including hyperbranching, multivalency, and well-defined uniform globular three-dimensional structures. In the current study, in order to enhance the transfection efficiency and reduce the cytotoxicity of PAMAMs, bromoalkylcarboxylates with different chain length (2-bromoacetic, 6-bromohexanoic, 10-bromodecanoic and 16-bromohexadecanoic acids) were covalently conjugated with 10% and 30% of primary amines of generation 4 and 5 (G4 and G5) of PAMAM dendrimers to increase the hydrophobicity of the carrier. At the next stage, the alkylcarboxylate-PAMAMs were pegylaed to further modify the PAMAM structures for biological applications. Obtained results demonstrated that the prepared PAMAM derivatives had particle size around 140 nm with net-positive surface charge. None of the prepared PAMAM-based non-viral vactors exhibited significant hemolytic activity and also cytotoxicity. Meanwhile decahexanoate-PAMAM G4 [G4(16C-10%)] and decanoate-PAMAM G4 conjugated to polyethylene glycol (PEG) (G4[(10C-30%)(10C-PEG)]) showed highest transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, interestingly only the latter had improved transfection efficiency in mesenchymal stem cells (MSCs). This study proved the potential utility of alkylcarboxylate-grafted PAMAM dendrimers (G4 and G5) with or without PEG modification for efficient gene transfer into cancerous cells as well as MSCs.

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Section: Discussionmentioning

confidence: 99%

Synthesis of efficient gene delivery systems by grafting pegylated alkylcarboxylate chains to PAMAM dendrimers: Evaluation of transfection efficiency and cytotoxicity in cancerous and mesenchymal stem cells

et al. 2015

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“…However, the use of viral vectors in human clinical trials raises significant safety issues, such as potential immunogenicity and reversion to pathogenicity 6 7 . This has encouraged the development of non-viral vectors with better biosafety profiles, including nanocomplexes based on dendrimers 8 , lipids, 9 or polysaccharides 10 .…”

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confidence: 99%

Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells

Santos-Carballal

Aaldering

Ritzefeld

et al. 2015

Sci Rep

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Cancer gene therapy requires the design of non-viral vectors that carry genetic material and selectively deliver it with minimal toxicity. Non-viral vectors based on cationic natural polymers can form electrostatic complexes with negatively-charged polynucleotides such as microRNAs (miRNAs). Here we investigated the physicochemical/biophysical properties of chitosan–hsa-miRNA-145 (CS–miRNA) nanocomplexes and the biological responses of MCF-7 breast cancer cells cultured in vitro. Self-assembled CS–miRNA nanocomplexes were produced with a range of (+/−) charge ratios (from 0.6 to 8) using chitosans with various degrees of acetylation and molecular weight. The Z-average particle diameter of the complexes was <200 nm. The surface charge increased with increasing amount of chitosan. We observed that chitosan induces the base-stacking of miRNA in a concentration dependent manner. Surface plasmon resonance spectroscopy shows that complexes formed by low degree of acetylation chitosans are highly stable, regardless of the molecular weight. We found no evidence that these complexes were cytotoxic towards MCF-7 cells. Furthermore, CS–miRNA nanocomplexes with degree of acetylation 12% and 29% were biologically active, showing successful downregulation of target mRNA expression in MCF-7 cells. Our data, therefore, shows that CS–miRNA complexes offer a promising non-viral platform for breast cancer gene therapy.

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“…To circumvent this problem, neutrally charged particles or negative charged naked pDNA or RNA itself have been explored. Proton-sponge polymers, including PAMAM and PEI exhibit pKa values between physiological and lysosomal pH, causing osmotic swelling and rupture of the endosome membrane, which releases of the polyplexes into the cytosol [40,64]. And, the application of dendrimer reported the higher attachment and prolonged retention of therapeutics in the ECM.…”

Section: Discussionmentioning

confidence: 99%

Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats

Lee

Choi

et al. 2016

Biomaterials

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In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM.

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PAMAM dendrimer roles in gene delivery methods and stem cell research

Cited by 24 publications

References 51 publications

Synthesis of efficient gene delivery systems by grafting pegylated alkylcarboxylate chains to PAMAM dendrimers: Evaluation of transfection efficiency and cytotoxicity in cancerous and mesenchymal stem cells

Synthesis of efficient gene delivery systems by grafting pegylated alkylcarboxylate chains to PAMAM dendrimers: Evaluation of transfection efficiency and cytotoxicity in cancerous and mesenchymal stem cells

Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells

Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats

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