Cyclodextrin-Modified Polyethylenimine Polymers for Gene Delivery

Pun, Suzie H.; Bellocq, Nathalie C.; Liu, Aijie; Greg, Jensen; Machemer, Todd; Quijano, Erlinda; Schluep, Thomas; Wen, Shu-Fen; Engler, Heidrun; Heidel, Jeremy D.; Davis, Mark E.

doi:10.1021/bc049891g

Cited by 291 publications

(240 citation statements)

References 30 publications

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“…Such a compound had been used in pDNA delivery with good results. 19,23 Tang et al used PEI-cyclodextrin as a novel multifunctional prodrug for codelivery of a conjugated chemotherapeutic agent, tegafur, and enhanced green fluorescent protein reporter plasmid DNA. 24 Similarly, Pack et al found that cyclodextrin-PEI was less toxic to HEK293 cells than PEI.…”

Section: Introductionmentioning

confidence: 99%

Low-weight polyethylenimine cross-linked 2-hydroxypopyl-ß-cyclodextrin and folic acid as an efficient and nontoxic siRNA carrier for gene silencing and tumor inhibition by VEGF siRNA

Li¹,

Wang²,

Zhang³

et al. 2013

IJN

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Background: Targeted delivery of small interfering RNA (siRNA) has been regarded as one of the most important technologies for the development of siRNA therapeutics. However, the need for safe and efficient delivery systems is a barrier to further development of RNA interference therapeutics. In this work, a nontoxic and efficient siRNA carrier delivery system of low molecular weight polyethyleneimine (PEI-600 Da) cross-linked with 2-hydroxypopyl-β-cyclodextrin (HP-β-CD) and folic acid (FA) was synthesized for biomedical application. Methods: The siRNA carrier was prepared using a simple method and characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. The siRNA carrier nanoparticles were characterized in terms of morphology, size and zeta potential, stability, efficiency of delivery, and gene silencing efficiency in vitro and in vivo. Results: The siRNA carrier was synthesized successfully. It showed good siRNA binding capacity and ability to protect siRNA. Further, the toxicity of the carrier measured in vitro and in vivo appeared to be negligible, probably because of degradation of the low molecular weight PEI and HP-β-CD in the cytosol. Flow cytometry and confocal microscopy confirmed that the FA receptor-mediated endocytosis of the FA-HP-β-CD-PEI/siRNA complexes was greater than that of the HP-β-CD-PEI/siRNA complexes in FA receptor-enriched HeLa cells. The FA-HP-β-CD-PEI/siRNA complexes also demonstrated excellent gene silencing efficiency in vitro (in the range of 90%), and reduced vascular endothelial growth factor (VEGF) protein expression in the presence of 20% serum. FA-HP-β-CD-PEI/siRNA complexes administered via tail vein injection resulted in marked inhibition of tumor growth and reduced VEGF protein expression in the tumors. Conclusion: Our results suggest that the FA-HP-β-CD-PEI complex is a nontoxic and highly efficient gene carrier with the potential to deliver siRNA for cancer gene therapy effectively in vitro and in vivo.

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Section: Introductionmentioning

confidence: 99%

Low-weight polyethylenimine cross-linked 2-hydroxypopyl-ß-cyclodextrin and folic acid as an efficient and nontoxic siRNA carrier for gene silencing and tumor inhibition by VEGF siRNA

Li¹,

Wang²,

Zhang³

et al. 2013

IJN

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“…Currently, there are several methods to deliver siRNA in vivo. These can be divided into physical and mechanical methods (hydrodynamic tail vein injections in mice 4,5,6 , electroporation 7,8,9 , ultrasound 10 , and the gene gun 11 ); local administration 3 (intravenous injection 12 , intraperitoneal injection, subcutaneous injection); and chemical methods (cationic lipids 13,14 , polymers 15,16,17,18,19,20 , and peptides 21,22,23,24 ). However, the delivery efficiency (desired dose), uncontrollable biodistribution and delivery-related toxicitities must be carefully analyzed.…”

Section: Discussionmentioning

confidence: 99%

Novel Cell type-specific aptamer-siRNA delivery system for HIV-1 therapy

Zhou

et al. 2007

Nat Prec

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SummaryThe successful use of small interfering RNAs (siRNAs) for therapeutic purposes requires safe and efficient delivery to specific cells and tissues. Here we demonstrate cell type-specific delivery of anti-HIV siRNAs via fusion to an anti-gp120 aptamer. The envelope glycoprotein is expressed on the surface of HIV-1 infected cells, allowing binding and interalization of the aptamer-siRNA chimeric molecules. We demonstrate that the anti-gp120 aptamer-siRNA chimera is specifically taken up by cells expressing HIV-1 gp120, and the appended siRNA is processed by Dicer, releasing an anti-tat/rev siRNA which in turn inhibits HIV replication. We show for the first time a dual functioning aptamer-siRNA chimera in which both the aptamer and the siRNA portions have potent anti-HIV activities and that gp120 expressed on the surface of HIV infected cells can be used for aptamer mediated delivery of anti-HIV siRNAs.RNA interference (RNAi) is a process of sequence-specific post-transcriptional gene silencing triggered by small interfering RNAs (siRNA). The silencing is sequence specific and one of the two strands of the siRNA guides the RNA induced silencing complex (RISC) to the complementary target, resulting in cleavage and subsequent destruction of the target RNA 1 . RNAi is rapidly becoming one of the methods of choice for gene function studies, and is also being exploited for therapeutic applications 2, 3 . The

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“…Sugar is a practically non-toxic polymer, in which the primary and secondary amines can be protonated in a physiological milieu. Sugar-based materials have been popularly used in gene delivery, while the transfection efficiencies are comparable to that of PEI [19].…”

Section: Resultsmentioning

confidence: 99%

Multifunctional PEG-grafted chitosan copolymer possessing amino and carboxyl (or formyl) groups

Liu

Wang

et al. 2010

Open Chemistry

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Cyclodextrin-Modified Polyethylenimine Polymers for Gene Delivery

Cited by 291 publications

References 30 publications

Low-weight polyethylenimine cross-linked 2-hydroxypopyl-ß-cyclodextrin and folic acid as an efficient and nontoxic siRNA carrier for gene silencing and tumor inhibition by VEGF siRNA

Low-weight polyethylenimine cross-linked 2-hydroxypopyl-ß-cyclodextrin and folic acid as an efficient and nontoxic siRNA carrier for gene silencing and tumor inhibition by VEGF siRNA

Novel Cell type-specific aptamer-siRNA delivery system for HIV-1 therapy

Multifunctional PEG-grafted chitosan copolymer possessing amino and carboxyl (or formyl) groups

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Cyclodextrin-Modified Polyethylenimine Polymers for Gene Delivery

Cited by 291 publications

References 30 publications

Low-weight polyethylenimine cross-linked 2-hydroxypopyl-&szlig;-cyclodextrin and folic acid as an efficient and nontoxic siRNA carrier for gene silencing and tumor inhibition by VEGF siRNA

Low-weight polyethylenimine cross-linked 2-hydroxypopyl-&szlig;-cyclodextrin and folic acid as an efficient and nontoxic siRNA carrier for gene silencing and tumor inhibition by VEGF siRNA

Novel Cell type-specific aptamer-siRNA delivery system for HIV-1 therapy

Multifunctional PEG-grafted chitosan copolymer possessing amino and carboxyl (or formyl) groups

Contact Info

Product

Resources

About

Low-weight polyethylenimine cross-linked 2-hydroxypopyl-ß-cyclodextrin and folic acid as an efficient and nontoxic siRNA carrier for gene silencing and tumor inhibition by VEGF siRNA

Low-weight polyethylenimine cross-linked 2-hydroxypopyl-ß-cyclodextrin and folic acid as an efficient and nontoxic siRNA carrier for gene silencing and tumor inhibition by VEGF siRNA