Anti-angiogenesis effect of generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide on breast cancer in vitro

Gu, Shanzhi; Zhao, Xinhan; Zhang, Lingxiao; Li, Li; Wang, Zhiyu; Meng, Min; An, Gaili

doi:10.1631/jzus.b0820175

Cited by 8 publications

(3 citation statements)

References 14 publications

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“…A full generation PAMAM dendrimer has primary amine groups on the surface (pKa =6.85) and tertiary amine groups within the core (pKa = 3.86) [31]. The high density of surface functional groups on PAMAM dendrimers presents the opportunity of functionalizing these polymers with various drugs, nucleic acids and imaging system components (Figure 2B) [32–39]. PAMAM dendrimers of certain generations and surface charge can permeate the epithelial barrier of the gut, suggesting their potential as oral drug carriers [6–28].…”

Section: Introductionmentioning

confidence: 99%

Transepithelial transport and toxicity of PAMAM dendrimers: Implications for oral drug delivery

Sadekar

Ghandehari

2012

Advanced Drug Delivery Reviews

271

202

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This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer – drug conjugates, as a function of physicochemical properties will further need to be assessed.

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Section: Introductionmentioning

confidence: 99%

Transepithelial transport and toxicity of PAMAM dendrimers: Implications for oral drug delivery

Sadekar

Ghandehari

2012

Advanced Drug Delivery Reviews

271

202

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“…The results were very promising as the lOnm wide and homogeneously netlike dendrimer complex showed an impressive buffering ability between a pH of 5-10, a transfection efficiency of 98.76% with a charge ratio of 1:40, and no toxicity on the cells. The results showed a marked decrease in VEGF protein and mRNA (42). In another study, Liu et al confirmed the promising anticancer effects of PAMAM dendrimers when they experimented with triethanolamine (TEA) core PAMAM dendrimers to deliver heat shock protein Hsp27 siRNA successfully in (PC-3) prostate cancer cells.…”

Section: Delivery Of Biomoleculesmentioning

confidence: 90%

Dendrimer Nanoparticles and Their Applications in Biomedicine

Paul

Shao

Burdon

et al. 2013

Nanomaterials in Drug Delivery, Imaging, and Tissue Engineering

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Dendrimers are a class of macromolecular materials with a highly branched three-dimensional structure. Since its inception in 1978, the dendrimers have attracted much attention for their biomedical applications. Structurally, dendrimers can be divided into three components: the core, the interior and the shell. The stepwise growth technique gives rise to nearly monodisperse polymeric tree-like macromolecules, which are essential for biological applications, since the monodispersity is a key factor for generation of reproducible structure that allows evaluation of the biological activity relating to specific structures. In addition, the reactive functional groups on the exterior give provision to modify its outer surface so as to achieve multivalent effects, such as improved pharmacokinetics, combined drug delivery, site specific delivery of therapeutics using targeting molecules, reduced cytotoxicity and limited long-term side effects. This chapter presents a basic concept of this evolving technology and explores the unique features of this nanomaterial for successful future applications as biotherapeutics.

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“…In a study of Gu et al a generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide (G4PA-MAM/VEGFASODN) compound showed significantly higher transfection rate in 48 h than that of the liposome group (P \ 0.05) without obvious toxicity on the cells. More importantly, the expressions of both VEGF protein and its mRNA after G4PAMAM/VEGFASODN transfection decreased markedly [73].…”

Section: Inhibiting Gene Expression By Antisense Oligonucleotides (Asmentioning

confidence: 94%

Emerging biotechnological strategies for non-viral antiangiogenic gene therapy

Liu

Zhang

2012

Angiogenesis

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Angiogenesis has emerged as a promising target of cancer treatment. With the development of biotechnology, major progress has been made in the exploring effective therapies on targeting tumor angiogenesis over the last 20 years. Gene therapy has attracted considerable interest by virtue of the capabilities of expressing sustained levels of therapeutic agents within cells of the patients. However, the major challenge of gene therapy is the efficient delivery of therapeutic gene to the target site. Compared with viral strategies, non-viral strategies were more acceptable by their widely recognized security and lower side effects. This paper reviews the basic biology of angiogenesis, the potential advantages of antiangiogenic gene therapy, the therapeutic genetic drugs developed through biotechnology, as well as the biotechnological strategies that enhancing non-viral gene therapy targeting to tumor angiogenesis in a more controlled manner, with great respect to RNA interference, ligand-directed vascular targeting strategies, vascular endothelial growth factor pathway and tumor associated macrophages targeting. In conclusion, antiangiogenic gene therapy holds great promise in advancing cancer therapy. Developing better non-viral biotechnological platforms will benefit antiangiogenic targeted cancer gene therapeutic methods, support their evaluation in human clinical trials and realize the actual utilization in the near future.

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Anti-angiogenesis effect of generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide on breast cancer in vitro

Cited by 8 publications

References 14 publications

Transepithelial transport and toxicity of PAMAM dendrimers: Implications for oral drug delivery

Transepithelial transport and toxicity of PAMAM dendrimers: Implications for oral drug delivery

Dendrimer Nanoparticles and Their Applications in Biomedicine

Emerging biotechnological strategies for non-viral antiangiogenic gene therapy

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