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Book ChapterDOI

Folate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy.

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TLDR
In a mouse xenograft model of HNSCC, the design and synthesis of fluorescently labeled, folic acid-decorated polyamidoamine generation 4 (G4) dendrimer conjugates for H NSCC-targeted gene delivery significantly enhances gene transfection or knockdown efficiency in HNS CC cells.
Abstract
Gene delivery systems have been developed on the basis of dendrimers and many other types of nanoparticle carriers, but few have been developed for head and neck squamous cell carcinomas (HNSCC). Herein, we describe the design and synthesis of fluorescently labeled, folic acid-decorated polyamidoamine (PAMAM) generation 4 (G4) dendrimer conjugates for HNSCC-targeted gene delivery. This delivery system comprises a dendrimer as the carrier that is conjugated with folic acid (FA) as HNSCC targeting moiety and imaging agents fluorescein isothiocyanate (FITC) or IRDye 800CW (NIR) for in vitro trafficking or bioimaging, respectively. By complexing with plasmid or siRNA, G4-FA/plasmid (or siRNA) significantly enhances gene transfection or knockdown efficiency in HNSCC cells. In a mouse xenograft model of HNSCC, this versatile G4-FA vector shows high biocompatibility, tumor targeting, high uptake, and sustained retention, making it a suitable platform for HNSCC gene therapy.

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Journal ArticleDOI

Dendrimers and hyperbranched structures for biomedical applications

TL;DR: Dendrimers can improve the bioavailability of drugs by increasing their solubility in water, and changing surface charge, thereby reducing toxicity.
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Recent Advances in Preclinical Research Using PAMAM Dendrimers for Cancer Gene Therapy.

TL;DR: A review of the development of poly(amidoamine) dendrimers in anticancer gene therapies is presented in this article, evaluating the advantages and disadvantages of the modification approaches and the nanomedicine regulatory issues preventing their translation into the clinical setting, highlighting important areas for further development and possible steps that seem promising in terms of development of PAMAM as a carrier of genetic material.
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An updated review of folate-functionalized nanocarriers: A promising ligand in cancer.

TL;DR: In this article, the authors highlight the latest developments on the use of folate-conjugated nanoparticles in cancer diagnosis and treatment, and discuss the toxicity, biocompatibility and efficacy of these nanocarriers.
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References
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Journal ArticleDOI

Designing dendrimers for biological applications.

TL;DR: Advances in understanding of the role of molecular weight and architecture on the in vivo behavior of dendrimers, together with recent progress in the design of biodegradable chemistries, has enabled the application of these branched polymers as anti-viral drugs, tissue repair scaffolds, targeted carriers of chemotherapeutics and optical oxygen sensors.
Journal ArticleDOI

Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay

TL;DR: Overall, this new methodology is reliable for determining functional FR expression levels in tissues, and it could possibly be a useful clinical test to determine patient candidacy for FR-targeted therapeutics.
Journal ArticleDOI

Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines: Physiologic and clinical implications

TL;DR: Little is known about the tissue specificities of FR β and FR‐α, but there is no report on the relative expression of FR‐β in any tissue other than in placenta.
Journal ArticleDOI

Structural basis for molecular recognition of folic acid by folate receptors

TL;DR: The extensive interactions between the receptor and ligand readily explain the high folate-binding affinity of folate receptors and provide a template for designing more specific drugs targeting the folate receptor system.
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