A review of RGD-functionalized nonviral gene delivery vectors for cancer therapy

Park, J; Singha, Kaushik; Son, Sejin; J, Kim; Namgung, Ran; Yun, Chae Ok; Wj, Kim

doi:10.1038/cgt.2012.64

Cited by 88 publications

(68 citation statements)

References 97 publications

(110 reference statements)

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“…The endometriosistargeting moiety of a delivery vehicle plays an important role in efficient treatment by not only reducing unwanted systemic toxicity but also overcoming dose limitation. 19 Therefore, we selected PEI and CSO systems, which were previously developed by our research group, and modified them by using HA to increase the localization of the polyplex in endometriosis microenvironment ( Figure 1A). Thus, we synthesized a novel gene carrier (CSO-PEI/siRNA)HA and evaluated its physicochemical properties, in vitro cytotoxicity and transfection efficiency, cellular uptake efficiency, in vivo biodistribution, therapeutic effect, and initial mechanism of siRNA gene therapy and explored the feasibility of siRNA gene therapy on endometriosis.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation

Zhao¹,

Cheng²,

Yan³

et al. 2016

IJN

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To identify a new drug candidate for treating endometriosis which has fewer side effects, a new polymeric nanoparticle gene delivery system consisting of polyethylenimine-grafted chitosan oligosaccharide (CSO-PEI) with hyaluronic acid (HA) and small interfering RNA (siRNA) was designed. There was no obvious difference in sizes observed between (CSO-PEI/siRNA)HA and CSO-PEI/siRNA, but the fluorescence accumulation in the endometriotic lesion was more significant for (CSO-PEI/siRNA)HA compared with CSO-PEI/siRNA due to the specific binding of HA to CD44. In addition, the (CSO-PEI/siRNA)HA nanoparticle gene therapy significantly decreased the endometriotic lesion sizes with atrophy and degeneration of the ectopic endometrium. The epithelial cells of ectopic endometrium from rat models of endometriosis showed a significantly lower CD44 expression than control after treatment with (CSO-PEI/siRNA)HA. Furthermore, observation under an electron microscope showed no obvious toxic effect on the reproductive organs. Therefore, (CSO-PEI/siRNA)HA gene delivery system can be used as an effective method for the treatment of endometriosis.

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Section: Introductionmentioning

confidence: 99%

Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation

Zhao¹,

Cheng²,

Yan³

et al. 2016

IJN

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“…As previously mentioned, simply adding the RGD tripeptide to target integrins significantly enhances non-viral gene delivery to HUVEC [39] and other cell types up to 50-fold [51–53]. Conjugation of small molecules like folate has also been shown to enhance the transfection of PEI–PEG hybrids while reducing serum scavenging and toxicity [54].…”

Section: Highly Evolved Hgt: Virusesmentioning

confidence: 99%

Applying horizontal gene transfer phenomena to enhance non-viral gene therapy

Elmer

Christensen

Rege

2013

Journal of Controlled Release

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Horizontal gene transfer (HGT) is widespread amongst prokaryotes, but eukaryotes tend to be far less promiscuous with their genetic information. However, several examples of HGT from pathogens into eukaryotic cells have been discovered and mimicked to improve non-viral gene delivery techniques. For example, several viral proteins and DNA sequences have been used to significantly increase cytoplasmic and nuclear gene delivery. Plant genetic engineering is routinely performed with the pathogenic bacterium Agrobacterium tumefaciens and similar pathogens (e.g. Bartonella henselae) may also be able to transform human cells. Intracellular parasites like Trypanosoma cruzi may also provide new insights into overcoming cellular barriers to gene delivery. Finally, intercellular nucleic acid transfer between host cells will also be briefly discussed. This article will review the unique characteristics of several different viruses and microbes and discuss how their traits have been successfully applied to improve non-viral gene delivery techniques. Consequently, pathogenic traits that originally caused diseases may eventually be used to treat many genetic diseases.

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“…However, genetic delivery methods have not yet been discovered; therefore, the same hurdles which inhibit all protein therapeutics preclude the feasibility of immunocytokines [11]. Alternatively, tumor-targeting peptides can easily be encoded into therapeutic plasmid DNA (pDNA), and the gene product can both home to distant tumors and deploy the immune-stimulating payload [12–14]. The peptide-cytokine VNTANST-IL12 can successfully perform these roles by targeting ectopically expressed cell-surface vimentin and utilizing the pleiotropic, antitumor cytokine IL12 [12, 15, 16].…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Tumor-Targeted Interleukin 12 Gene Therapy in Treated and Non-Treated, Metastatic Lesions

Cutrera¹,

King²,

Jones³

et al. 2014

CGT

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The ability to control the immune system to actively attack tumors would be a marvelous weapon to combat the incessant attack of cancer. Unfortunately, safe and effective methods are not yet available. To overcome the impediments to this control, tumor-targeted (tt) Interleukin (IL) 12 plasmid DNA can be safely delivered to accessible tumors, and these treatments can induce antitumor immune responses in both the treated and untreated tumors. Here, electroporation-mediated ttIL12 pDNA treatments are shown to be safe and well tolerated in a dose escalation study in canines bearing naturally-occurring neoplasms. The final patient received treatment with up to 3,800 μg pDNA distributed throughout five separate squamous cell carcinoma tumors, doses equivalent to those administered in a Phase I trial with wildtype IL12 pDNA. Not a single severe adverse event occurred in any patient at any of the five dose levels, and only minor, transient changes were noted in any tested parameter. Clinical response analysis and immune marker mRNA detection of treated and non-treated lesions confirmed that the ttIL12 pDNA treatments in only a few tumors could elicit antitumor immune responses in the treated lesions as well as distant metastatic lesions. These observations and results prove that ttIL12 pDNA can be safely administered at clinical levels, and these treatments can effect both treated and non-treated, metastatic lesions.

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A review of RGD-functionalized nonviral gene delivery vectors for cancer therapy

Cited by 88 publications

References 97 publications

Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation

Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation

Applying horizontal gene transfer phenomena to enhance non-viral gene therapy

Safety and Efficacy of Tumor-Targeted Interleukin 12 Gene Therapy in Treated and Non-Treated, Metastatic Lesions

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