Folic Acid-Decorated Polyamidoamine Dendrimer Mediates Selective Uptake and High Expression of Genes in Head and Neck Cancer Cells

Xu, Leyuan; Kittrell, Shannon; Yeudall, W. Andrew

doi:10.2217/nnm-2016-0244

Cited by 33 publications

(27 citation statements)

References 46 publications

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“…For example, an optimal amount of FA moieties (0.1–0.2 μmol FA/mg polymer) was reported, above which the uptake of FA-nanogels was gradually decreased [50]. Similarly, we found excess amount of G4-FA conjugates could suppress the cellular uptake of conjugates themselves, most likely due to the saturation of FR on the cell surface [53]. The fundamental understanding of FA-conjugated nanoparticles as targeting vectors can help investigators to better design drug delivery systems for the cancers with high FR expression.…”

Section: Fa-decorated Nanomedicinesmentioning

confidence: 67%

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Folate-mediated chemotherapy and diagnostics: An updated review and outlook

Bai

Zhang

et al. 2017

Journal of Controlled Release

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Folate receptor (FR) is highly expressed in many types of human cancers, and it has been actively studied for developing targeted chemotherapy and diagnostic agents. Tremendous efforts have been made in developing FR-targeted nanomedicines and nanoprobes and translating them into clinical applications. This article provides a concise review on the latest development of folate-mediated nanomedicines and nanoprobes for chemotherapy and diagnostics with an emphasis on in vivo applications. The cellular uptake mechanisms, pharmacokinetics (PK), administration routes and major challenges in FR-targeted nanoparticles are discussed.

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Section: Fa-decorated Nanomedicinesmentioning

confidence: 67%

“…Furthermore, we found G4-FA was preferentially taken up by HN12 (FR-high) but not U87 (FR-low) cells in a co-culture model. As a result, G4-FA showed a higher cytocompatibility and transfection efficiency than none targeted dendrimer in FR-high cells such as HN12 and T98 [53]. …”

Section: Fa-decorated Nanomedicinesmentioning

confidence: 99%

Folate-mediated chemotherapy and diagnostics: An updated review and outlook

Bai

Zhang

et al. 2017

Journal of Controlled Release

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“…Gal-G5/CEH complexes (2.5, 5, 10, 20, 40 and 50, w/w) and G5/CEH (0.25, 0.5, 1, 2, 4 and 8, w/w) were prepared following a procedure described earlier [23, 42]. The complexes were mixed with loading buffer and loaded onto a 0.8 % agarose gel containing ethidium bromide.…”

Section: Methodsmentioning

confidence: 99%

Bolstering cholesteryl ester hydrolysis in liver: A hepatocyte-targeting gene delivery strategy for potential alleviation of atherosclerosis

Lancina

Wang

et al. 2017

Biomaterials

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Current atherosclerosis treatment strategies primarily focus on limiting further cholesteryl esters (CE) accumulation by reducing endogenous synthesis of cholesterol in the liver. No therapy is currently available to enhance the removal of CE, a crucial step to reduce the burden of the existing disease. Given a central role of hepatic cholesteryl ester hydrolase (CEH) in intrahepatic hydrolysis of CE and subsequent removal of the resulting free cholesterol, in this work, we applied galactose-functionalized polyamidoamine (PAMAM) dendrimer G5 (Gal-G5) for hepatocyte-specific delivery of CEH expression vector. The data presented herein show increased specific uptake of Gal-G5 by the hepatocytes in vitro and in vivo. Furthermore, the upregulated CEH expression in the hepatocytes significantly enhanced intracellular hydrolysis of HDL-CE and subsequent conversion/secretion of hydrolyzed free cholesterol (FC) as bile acids. Increased CEH expression in the liver significantly increased the flux of HDL-CE to biliary as well as fecal FC and bile acids. Meanwhile, Gal-G5 did not induce hepatic or renal toxicity. It was not immunotoxic. Because of these encouraging pre-clinical testing results, using this safe and highly efficient hepatocyte-specific gene delivery platform to enhance the hepatic processes involved in cholesterol elimination is a promising strategy for alleviation of atherosclerosis.

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“…Mechanistically, we found that G4-FA could be preferentially taken up by HN12 cells, in which folate receptor α (FRα) is highly expressed, compared to low FRα-expressing U87 cells. In addition, G4-FA competes with free FA for the FRα on the surface of HN12 cells and facilitates FR-dependent cellular uptake of complexed plasmid DNA [10]. …”

Section: Introductionmentioning

confidence: 99%

“…injection for administration of targeted therapy as it would allow substantial accumulation of nanoparticles at the tumor site and reduce toxicity to the normal tissues. Our recent work showed that G4-FA facilitated the entry of plasmid DNA into HN12 cells via FRα-mediated endocytosis at a rate much lower than that of non-specific absorptive endocytosis of plasmid mediated by unmodified G4 [10]. We hypothesized that a controlled slow tumor-specific cellular uptake mechanism would promote greater nanoparticle uptake in the tumor and enhance therapeutic effectiveness.…”

Section: Introductionmentioning

confidence: 99%

Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery

Yeudall

Yang

2017

Acta Biomaterialia

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The utility of folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) as a vector was investigated for local delivery of siRNA. In a xenograft HN12 (or HN12-YFP) tumor mouse model of head and neck squamous cell carcinomas (HNSCC), intratumorally (i.t.) injected G4-FA exhibited high tumor uptake and sustained highly localized retention in the tumors according to near infrared (NIR) imaging assessment. siRNA against vascular endothelial growth factor A (siVEGFA) was chosen as a therapeutic modality. Compared to the nontherapeutic treatment groups (PBS solution or dendrimer complexed with nontherapeutic green fluorescent protein siRNA [siGFP]), G4-FA/siVEGFA showed tumor inhibition effects in single-dose and two-dose regimen studies. In particular, two doses of G4-FA/siVEGFA i.t. administered eight days apart resulted in a more profound inhibition of tumor growth, accompanied with significant reduction in angiogenesis, as judged by CD31 staining and microvessel counts. Tumor size reduction in the two-dose regimen study was ascertained semi-quantitatively by live fluorescence imaging of YFP tumors and independently supported antitumor effects of G4-FA/siVEGFA. Taken together, G4-FA shows high tumor uptake and sustained retention properties, making it a suitable platform for local delivery of siRNAs to treat cancers that are readily accessible such as HNSCC.

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Folic Acid-Decorated Polyamidoamine Dendrimer Mediates Selective Uptake and High Expression of Genes in Head and Neck Cancer Cells

Cited by 33 publications

References 46 publications

Folate-mediated chemotherapy and diagnostics: An updated review and outlook

Folate-mediated chemotherapy and diagnostics: An updated review and outlook

Bolstering cholesteryl ester hydrolysis in liver: A hepatocyte-targeting gene delivery strategy for potential alleviation of atherosclerosis

Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery

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