Polyamidoamine (PAMAM) dendrimers modified with short oligopeptides for early endosomal escape and enhanced gene delivery

Thủy, Lê Thị Thanh; Mallick, Sudipta; Choi, Joon Sig

doi:10.1016/j.ijpharm.2015.07.017

Cited by 32 publications

(24 citation statements)

References 41 publications

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“…Previous studies have shown that PAMAM-FHR displays a high transfection efficiency and rapid endosomal escape due to its proton sponge effect [18,32]. Therefore, a gene transfection efficiency with this complex was evaluated by a luciferase assay based on a pCN-luc reporter gene system.…”

Section: Resultsmentioning

confidence: 99%

“…PAMAM-FHR was synthesized as reported previously [18]. The overall synthesis scheme is shown in Figure S1.…”

Section: Methodsmentioning

confidence: 99%

“…When the PMAMA-FHR/DNA complexes enter the cells, the polymer peptide bonds are hydrolyzed by peptidases, facilitating DNA release within the cell by virtue of the positive charge density. The subsequent membrane disruption results in rapid endosomal escape into the cytosol and increased effectiveness of the gene delivery carrier [18,19,20]. Moreover, previous reports showed that the influenza virus-inspired polymer carrier, A-C3, undergoes endosomal escape allowing for the release of siRNA via self-catalyzed polymer degradation without external release stimuli inducing pH, light, enzyme degradation, and redox potential [21,22].…”

Section: Introductionmentioning

confidence: 99%

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Polyplexes of Functional PAMAM Dendrimer/Apoptin Gene Induce Apoptosis of Human Primary Glioma Cells In Vitro

et al. 2019

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: Highly efficient and safe gene delivery has become an important aspect of neuronal gene therapy. We evaluated the ability of polyamidoamine (PAMAM) dendrimer grafted with phenylalanine, histidine, and arginine (PAMAM-FHR), a nonviral gene delivery vector, to deliver a therapeutic, tumor cell-specific killer gene, apoptin, into the human primary glioma cell line GBL-14 and human dermal fibroblasts. We performed a transfection assay using plasmids of luciferase and enhanced green fluorescent protein (EGFP) and assessed cell viability. Both cell lines were treated with complexes of PAMAM-FHR and apoptin after which their intracellular uptake and localization were examined by fluorescence-activated cell sorting (FACS)analysis and confocal laser scanning microscopy. Confocal microscopy showed that the PAMAM-FHR escaped from the endo-lysosome into the cytosol. Cell cycle phase distribution analysis, annexin V staining, and a tetramethylrhodamine ethyl ester (TMRE) assay established that apoptin triggered apoptosis in the GBL-14 cell line but not in normal fibroblasts. These results indicated that the PAMAM-FHR/apoptin complex is an effective gene vehicle for cancer therapy in vitro.

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Section: Resultsmentioning

confidence: 99%

“…PAMAM-FHR was synthesized as reported previously [18]. The overall synthesis scheme is shown in Figure S1.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polyplexes of Functional PAMAM Dendrimer/Apoptin Gene Induce Apoptosis of Human Primary Glioma Cells In Vitro

et al. 2019

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“…In recent years, the utilization of nanoparticles in plant biology has been considered because of advantages such as their capability for interaction with DNA and its protection against mechanical and enzymatic shearing (Bande et al, 2015), and also macromolecules' transfer into intact plant cells (Pasupathy et al, 2008;Liu et al, 2009;Naqvi et al, 2012). Dendrimers with different generations and surface groups have been synthesized, characterized, and tested in a wide range of animal cells (Mallick and Choi, 2015;Urbiola et al, 2015). However, there are few reports on the utilization of dendrimers as gene delivery carriers for plant cells (Pasupathy et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-enhanced gene delivery to alfalfa cells by hPAMAM dendrimer nanoparticles

Amani¹,

Zare²,

Asadi³

et al. 2018

Turk J Biol

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Cationic polyamidoamine (PAMAM) dendrimers are highly branched nanoparticles with unique molecular properties, which make them promising nanocarriers for gene delivery into cells. This research evaluated the ability of hyperbranched PAMAM (hPAMAM)-G2 with a diethylenetriamine core to interact with DNA, its protection from ultrasonic damage, and delivery to alfalfa cells. Additionally, the effects of ultrasound on the efficacy of hPAMAM-G2 for the delivery and expression of the gusA gene in the alfalfa cells were investigated. The electrophoresis retardation of plasmid DNA occurred at an N/P ratio (where N is the number of hPAMAM nitrogen atoms and P is the number of DNA phosphorus atoms) of 3 and above, and hPAMAM-G2 dendrimers completely immobilized the DNA at an N/P ratio of 4. The analysis of the DNA dissociated from the dendriplexes revealed a partial protection of the DNA from ultrasound damage at N/P ratios lower than 2, and with increasing N/P ratios, the DNA was better protected. Sonication of the alfalfa cells in the presence of ssDNA-FITC-hPAMAM increased the ssDNA delivery efficiency to 36%, which was significantly higher than that of ssDNA-FITC-hPAMAM without sonication. Additionally, the efficiency of transfection and the expression of the gusA gene were dependent on the N/P ratio and the highest efficiency (1.4%) was achieved at an N/P ratio of 10. The combination of 120 s of ultrasound and hPAMAM-DNA increased the gusA gene transfection and expression to 3.86%.

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“…6, the blends showed a clearly timedependent DOX accumulation in the nucleus, as observed by the red uorescence localized in endosome/lysosome compartments aer 4 h incubation and following colocalization of red uorescence with that from DAPI aer 12 and 24 h incubation. 39 The endosomal/lysosomal escape was probably attributed to the proton sponge effect caused by the PHIS block protonation in the acidic compartments of endosome or lysosome, leading to the endosome osmotic swelling, disruption of the endosomal/lysosomal membrane and cytoplasmic release of incorporated drug. 7.…”

Section: Cellular Uptakementioning

confidence: 99%

Doxorubicin-loaded pH-sensitive polymeric blends for synergistic cancer treatment

Wang

Zhang

et al. 2016

RSC Adv.

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An intelligentized system that can transport chemotherapeutics to targets in tumors is an attractive strategy to reverse drug resistance in tumor cells. In this work, a doxorubicin (DOX) delivery system composed of PEGylated resveratrol (PEG-GLY-RES) and poly(histidine)-PEG (PEG-PHIS) was prepared, characterized and evaluated for synergistic cancer therapy. RES was chemically linked with PEG as a component and DOX was loaded into the polymeric blends. This system had an average size of 80 nm, and showed the desired pH-dependent drug release properties, with much faster drug release at pH 5.5, mimicking the tumoral microenvironment. The MTT assay showed the drug loaded blends had higher cytotoxicity than free DOX in all doses. Confocal laser scanning microscopy observation and flow cytometry analyses indicated that the blends were efficiently internalized into HeLa cells, released DOX into the cytoplasm, and entered the nuclei. Endocytosis inhibition results proved that the blends entered the HeLa cells mainly through clathrin-mediated endocytosis and macropinocytosis. It has been shown that such co-delivery of RES and DOX is promising for improvement of anti-cancer efficacy.Scheme 1 Drug loaded polymeric blends as emerging controlled drug release systems.31168 | RSC Adv., 2016, 6, 31167-31176This journal is

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Polyamidoamine (PAMAM) dendrimers modified with short oligopeptides for early endosomal escape and enhanced gene delivery

Cited by 32 publications

References 41 publications

Polyplexes of Functional PAMAM Dendrimer/Apoptin Gene Induce Apoptosis of Human Primary Glioma Cells In Vitro

Polyplexes of Functional PAMAM Dendrimer/Apoptin Gene Induce Apoptosis of Human Primary Glioma Cells In Vitro

Ultrasound-enhanced gene delivery to alfalfa cells by hPAMAM dendrimer nanoparticles

Doxorubicin-loaded pH-sensitive polymeric blends for synergistic cancer treatment

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