Folate-PEG-Appended Dendrimer Conjugate with α-Cyclodextrin as a Novel Cancer Cell-Selective siRNA Delivery Carrier

Arima, Hisatomi; Yoshimatsu, Ayumi; Ikeda, Haruna; Ohyama, Ayumu; Motoyama, Keiichi; Higashi, Taishi; Tsuchiya, Akira; Niidome, Takuro; Katayama, Yoshiki; Hattori, Kiyohiko; Takeuchi, Tomoko

doi:10.1021/mp300188f

Cited by 90 publications

(103 citation statements)

References 38 publications

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“…Folate-PEG-appended α-CDE as Tumor-Selective siRNA Carriers Arima et al 46,47) prepared folate-PEGappended α-CDE (G3) (Fol-PαC (G3)) as cancer cell-selective gene and siRNA carriers (Fig. 6).…”

Section: Lactose-peg-appended α-Cde As Hepatocyteselective Gene and Smentioning

confidence: 99%

“…Additionally, the siRNA/Fol-PαC (G3) complex indicated in vivo RNAi effects following systemic injection in tumor cells-bear- ing mice. 47) However, little RNAi effect was observed. Thus, Ohyama et al 48) prepared Fol-PαC (G4) to increase the in vivo siRNA delivery efficiency of Fol-PαC (G3).…”

Section: Lactose-peg-appended α-Cde As Hepatocyteselective Gene and Smentioning

confidence: 99%

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Potential Use of Cyclodextrins as Drug Carriers and Active Pharmaceutical Ingredients

2017

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Cyclodextrins (CyDs) are extensively used in various fields, and especially have been widely utilized as pharmaceutical excipients and drug carriers in the pharmaceutical field. Owing to the multi-functional and biocompatible characteristics, CyDs can improve the undesirable properties of drug molecules. This review outlines the current application of CyDs in pharmaceutical formulations, focusing on their use as CyD-based drug carriers for several kinds of drugs. Additionally, CyDs have great potential as active pharmaceutical ingredients against various diseases with few side effects.

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Section: Lactose-peg-appended α-Cde As Hepatocyteselective Gene and Smentioning

confidence: 99%

Section: Lactose-peg-appended α-Cde As Hepatocyteselective Gene and Smentioning

confidence: 99%

Potential Use of Cyclodextrins as Drug Carriers and Active Pharmaceutical Ingredients

2017

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“…PME with a PAMAM G2.5 core and PEI 423 outer layers (G2.5−PEI 423) was synthesized according to our previous report. 37 The conjugation of COOH-PEG 3.4k -FA 1 or COOH-PEG 3.4k -FA 2 to PME was performed using the method reported by Arima et al 41 In brief, 6.6 μmol (2 equiv to PME) of COOH-PEG 3.4k -FA 1 , COOH-PEG 3.4k -FA 2 or COOH-PEG 3.5k -OH was dissolved in 0.2 M borate buffer containing EDC and NHS and stirred at room temperature for 2 h in the dark. Then, they were added to PME solution (0.05 g, 3.3 μmol) and reacted for 48 h, respectively.…”

Section: ■ Introductionmentioning

confidence: 99%

Divalent Folate Modification on PEG: An Effective Strategy for Improving the Cellular Uptake and Targetability of PEGylated Polyamidoamine–Polyethylenimine Copolymer

et al. 2014

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The stability and targeting ability of nanocarrier gene delivery systems are necessary conditions to ensure the good therapeutic effect and low nonspecific toxicity of cancer treatment. Poly(ethylene glycol) (PEG) has been widely applied for improving stability and as a spacer for linking ligands and nanocarriers to improve targetability. However, the cellular uptake and endosomal escape capacity of nanocarriers has been seriously harmed due to the introduction of PEG. In the present study, we synthesized a new gene delivery vector by coupling divalent folate-PEG (PEG3.4k-FA2) onto polyamidoamine-polyethylenimine (PME) copolymer (PME-(PEG3.4k-FA2)1.72). Both PEG and monovalent folate-PEG (PEG3.4k-FA1) modified PME were prepared as control polymers, which were named as PME-(PEG3.5k)1.69 and PME-(PEG3.4k-FA1)1.66, respectively. PME-(PEG3.4k-FA2)1.72 exhibited strong DNA condensation capacity like parent polymer PME which was not significantly influenced by PEG. PME-(PEG3.4k-FA2)1.72/DNA complexes at N/P = 10 had a diameter ∼143 nm and zeta potential ∼13 mV and showed the lowest cytotoxicity and hemolysis and the highest transfection efficiency among all tested polymers. In folate receptor positive (FR-positive) cells, the cellular uptake and transfection efficiency were increased with the increase in the number of folates coupled on PEG; the order was PME-(PEG3.4k-FA2)1.72 > PME-(PEG3.4k-FA1)1.66 > PME-(PEG3.5k)1.69. Folate competition assays showed that PME-(PEG3.4k-FA2)1.72 complexes had stronger targeting ability than PME-(PEG3.5k)1.69 and PME-(PEG3.4k-FA1)1.66 complexes due to their higher folate density per PEG molecule. Cellular uptake mechanism study showed that the folate density on PEG could change the endocytosis pathway of PME-(PEG3.5k)1.69 from clathrin-mediated endocytosis to caveolae-mediated endocytosis, leading to less lysosomal degradation. Distribution and uptake in 3D multicellular spheroid assays showed that divalent folate could offer PME-(PEG3.4k-FA2)1.72 complexes stronger penetrating ability and higher cellular uptake. With these advantages, PME-(PEG3.4k-FA2)1.72 may be a promising nonviral vector candidate for efficient gene delivery. This study also indicates that divalent folate modification on PEG can serve as an efficient strategy to improve the cellular uptake and targeting ability of PEGylated cationic polymers for gene delivery.

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“…They are considered to be non-immunogenic and non-genotoxic and show low toxicity toward cells. PAMAMs are thought to be useful as transfection vehicles for plasmid DNA (Santos et al, 2010), particularly for siRNA (Ofek et al, 2010;Liu et al, 2011;Arima et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Efficient delivery of connective tissue growth factor shRNA using PAMAM nanoparticles

Huang¹,

Yi²,

Yuan³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to detect the anti-fibrosis activity of connective tissue growth factor (CTGF) small hairpin RNA (shRNA) mediated by polyamidoamine dendrimer nanoparticles in rat myocardial cell lines and myocardium. CTGF shRNAs were constructed from inverted oligonucleotides and a polyamidoamine nanoparticle vector was used to transfer shRNA into H9c2 myocardial cells and spontaneously hypertensive rats. The expression of CTGF, transforming growth factor-b 1 , and laminin were measured by semi-quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. pCTGF-shRNA significantly reduced CTGF upregulation induced by angiotensin II in H9c2 myocardial cells. The mRNA and protein expression of CTGF and laminin in pCTGF-shRNAtransferred spontaneously hypertensive rats decreased significantly compared to the control group and pHK-shRNA group (P < 0.05). The expression of transforming growth factor-b 1 showed no significant difference among the 3 groups (P > 0.05). pCTGF-shRNA mediated by polyamidoamine can be used to successfully reduce myocardial CTGF and laminin expression, suggesting that this system can be used to improve myocardial fibrosis therapy.

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Folate-PEG-Appended Dendrimer Conjugate with α-Cyclodextrin as a Novel Cancer Cell-Selective siRNA Delivery Carrier

Cited by 90 publications

References 38 publications

Potential Use of Cyclodextrins as Drug Carriers and Active Pharmaceutical Ingredients

Potential Use of Cyclodextrins as Drug Carriers and Active Pharmaceutical Ingredients

Divalent Folate Modification on PEG: An Effective Strategy for Improving the Cellular Uptake and Targetability of PEGylated Polyamidoamine–Polyethylenimine Copolymer

Efficient delivery of connective tissue growth factor shRNA using PAMAM nanoparticles

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