PEI-<i>g</i>-PEG-RGD/Small Interference RNA Polyplex-Mediated Silencing of Vascular Endothelial Growth Factor Receptor and Its Potential as an Anti-Angiogenic Tumor Therapeutic Strategy

Kim, Jihoon; Kim, Sung Wan; Kim, Won Jong

doi:10.1089/oli.2011.0278

Cited by 31 publications

(20 citation statements)

References 37 publications

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“…Arginine-glycine-aspartate peptides (RGD) are known to traverse through the plasma membrane passively and localize to the cytoplasm, making them an efficient siRNA carrier. PEI-g-PEG-RGD linked to VEGFR1 siRNA through a PEG spacer was systemically delivered to solid murine tumors, resulting in angiogenesis inhibition in tumor (161). RGD peptide-labeled with chitosan nanoparticle was also reported to be effective in tumor targeted delivery and silencing multiple growth-promoting genes in tumor bearing mice (162).…”

Section: Complexationmentioning

confidence: 99%

Subcellular Fate and Off-Target Effects of siRNA, shRNA, and miRNA

2011

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RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA). As this is a highly specific technique, efforts have been made to utilize RNAi towards potential knock down of disease-causing genes in a targeted fashion. RNAi has the potential to selectively inhibit gene expression by degrading or blocking the translation of the target mRNA. However, delivering these RNAs to specific cells presents a significant challenge. Some of these challenges result from the necessity of traversing the circulatory system while avoiding kidney filtration, degradation by endonucleases, aggregation with serum proteins, and uptake by phagocytes. Further, non-specific delivery may result in side-effects, including the activation of immune response. We discuss the challenges in the systemic delivery to target cells, cellular uptake, endosomal release and intracellular transport of RNAi drugs and recent progress in overcoming these barriers. We also discuss approaches that increase the specificity and metabolic stability and reduce the off-target effects of RNAi strategy.

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Section: Complexationmentioning

confidence: 99%

Subcellular Fate and Off-Target Effects of siRNA, shRNA, and miRNA

2011

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“…Kim et al modified a branched PEI with the integrin binding peptide Arg-Gly-Asp (RGD) through a PEG spacer [115]. At an N/P ratio of 10, the resulting nanoparticles loaded with vascular endothelial growth factor receptor 1 (VEGFR1) siRNA inhibited the growth of murine colon adenocarcinoma for 11 days.…”

Section: Polymeric Sirna Delivery Systemsmentioning

confidence: 99%

Recent In Vivo Evidences of Particle-Based Delivery of Small-Interfering RNA (siRNA) into Solid Tumors

Wen

Meng

2014

J Pharm Innov

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Small-interfering RNA (siRNA) is both a powerful tool in research and a promising therapeutic platform to modulate expression of disease-related genes. Malignant tumors are attractive disease targets for nucleic acid-based therapies. siRNA directed against oncogenes, and genes driving metastases or angiogenesis have been evaluated in animal models and in some cases, in humans. The outcomes of these studies indicate that drug delivery is a significant limiting factor. This review provides perspectives on in vivo validated nanoparticle-based siRNA delivery systems. Results of recent advances in liposomes and polymeric and inorganic formulations illustrate the need for mutually optimized attributes for performance in systemic circulation, tumor interstitial space, plasma membrane, and endosomes. Physiochemical properties conducive to efficient siRNA delivery are summarized and directions for future research are discussed.

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“…The three amino-acid peptide, Arg-Gly-Asp (RGD) has been extensively used as a ligand for targeting the cell-surface integrin receptor α v β 3 /α v β 5 , which is an important biomarker overexpressed in sprouting tumor vessels and most tumor cells [111, 112]. A cancer cell-specific replicating oncolytic Ad (Ad-DB7-U6shIL8) expressing short hairpin RNA (shRNA) against interleukin-8 (IL-8) mRNA, a potent pro-angiogenic factor, was physically complexed with the poly(CBA-DAH)-PEG-RGD polymers [105].…”

Section: Disease Applications Of Bioreducible Polymersmentioning

confidence: 99%

Bioreducible polymers for therapeutic gene delivery

Lee

Kim

2014

Journal of Controlled Release

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Most currently available cationic polymers have significant acute toxicity concerns such as cellular toxicity, aggregation of erythrocytes, and entrapment in the lung capillary bed, largely due to their poor biocompatibility and non-degradability under physiological conditions. To develop more intelligent polymers, disulfide bonds are introduced in the design of biodegradable polymers. Herein, the sustained innovations of biomimetic nanosized constructs with bioreducible poly(disulfide amine)s demonstrate a viable clinical tool for the treatment of cardiovascular disease, anemia, diabetes, and cancer.

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PEI-g-PEG-RGD/Small Interference RNA Polyplex-Mediated Silencing of Vascular Endothelial Growth Factor Receptor and Its Potential as an Anti-Angiogenic Tumor Therapeutic Strategy

Cited by 31 publications

References 37 publications

Subcellular Fate and Off-Target Effects of siRNA, shRNA, and miRNA

Subcellular Fate and Off-Target Effects of siRNA, shRNA, and miRNA

Recent In Vivo Evidences of Particle-Based Delivery of Small-Interfering RNA (siRNA) into Solid Tumors

Bioreducible polymers for therapeutic gene delivery

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