Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality
            <i>in vivo</i>
            imaging

Bartlett, Derek W.; Su, Helen C.; Hildebrandt, Isabel J.; Weber, Wolfgang; Davis, Mark E.

doi:10.1073/pnas.0707461104

Cited by 743 publications

(593 citation statements)

References 27 publications

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“…Recently, this group correlated the functional efficacy of polyplexes with biodistribution data using multimodal in vivo imaging in mice. 45 Although PET imaging demonstrated similar tumor localization for both nontargeted and transferrin-targeted siRNA nanoparticles, the latter showed higher functional activity in tumors as monitored by in vivo luciferase imaging. This is consistent with the notion that receptor-mediated cellular uptake into tumor cells by the transferrin receptor is essential for effective siRNA delivery.…”

Section: Combinatorial Chemistry Allows Rapid Polymer Development Formentioning

confidence: 96%

“…This is consistent with the notion that receptor-mediated cellular uptake into tumor cells by the transferrin receptor is essential for effective siRNA delivery. 45 Other examples of siRNA polyplexes for receptor-targeted in vivo delivery were recently reported, such as hepatocyte targeting utilizing the asialoglycoprotein receptor, 36 or brain targeting with a rabies virus-derived peptide ligand for the acetyl-choline receptor. 46 Multifunctional polymers can be designed with defined topology and dynamic transport domains…”

Section: Combinatorial Chemistry Allows Rapid Polymer Development Formentioning

confidence: 99%

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Gene therapy progress and prospects: synthetic polymer-based systems

2008

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Low efficiency, significant toxicity, polymer polydispersity and poorly understood delivery mechanisms have initially plagued the field of polymer-based gene therapy. Numerous strategies have helped to improve polyplexes, including the development of biodegradable polymers with reduced toxicity, incorporation of cell targeting, surface shielding and additional transport domains for effective and specific delivery, or improved chemistry for syntheses of polymers with uniform size and topology. Combined biooptical imaging and bioinformatics, providing insights into transfer bottlenecks, have helped to design improved polyplexes. Bioresponsive multifunctional polymers adapt in a dynamic manner to delivery barriers for efficient transfer of pDNA or siRNA to the target site.

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Section: Combinatorial Chemistry Allows Rapid Polymer Development Formentioning

confidence: 96%

Section: Combinatorial Chemistry Allows Rapid Polymer Development Formentioning

confidence: 99%

Gene therapy progress and prospects: synthetic polymer-based systems

2008

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“…PET and SPECT utilize radioisotopes such as 64 Cu, 111 In and 99m Tc, the chelates of which can be conjugated to nanoparticles similar to that of Gd 3+ . For example, 64 Cu-DOTA was linked to siRNA, which is in turn conjugated to transferrin targeted polycation nanoparticles for combined cancer imaging and treatment [159]. The bio-distribution of the nanoparticles was readily obtained in overlaid CT/PET images.…”

Section: Nanoparticles For Combined Imaging and Therapymentioning

confidence: 99%

“…The iron oxide cores provide MRI signal contrast and magneto-mobility. Multifunctional nanoparticles were constructed by simultaneously conjugating siRNA, near infrared fluorophores (Cy5.5) Chemical conjugation [155,156,160,166] Encapsulation (liposomes) [154] Hydrophobic interaction (micelles and nanoparticles coated with amphiphilic polymers) [147150] Electrostatic interaction (positively charged liposomes, polymers and mesoporous silica) [144,159] Degradability (pH sensitive, enzyme cleavable, and reducible bonds) [160,166] Heat generation (infrared laser, alternating magnetic field and ultrasound) [145,165] Magneto-mobility (magnetic nanoparticles) [144,167,168] Photosensitizer [162] and cell membrane translocation peptides to dextran coated iron oxide nanoparticles [155]. Tumor accumulation of the nanoparticles was confirmed with both MRI T 2 imaging and fluorescence imaging and was in good agreement with the knockdown effects of siRNAs.…”

Section: Nanoparticles For Combined Imaging and Therapymentioning

confidence: 99%

Engineering imaging probes and molecular machines for nanomedicine

Tong

Cradick

et al. 2012

Sci. China Life Sci.

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Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures and devices with proteins and nucleic acids, the design, synthesis and application of nanoprobes, nanocarriers and nanomachines provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of functional nanoparticle based molecular imaging probes, nano-structured materials as drug/gene carriers for in vivo delivery, and engineered molecular machines for treating single-gene disorders. This review focuses on the development of molecular imaging probes and engineered nucleases for nanomedicine, including quantum dot bioconjugates, quantum dot-fluorescent protein FRET probes, molecular beacons, magnetic and gold nanoparticle based imaging contrast agents, and the design and validation of zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) for gene targeting. The challenges in translating nanomedicine approaches to clinical applications are discussed. Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, biology, and medicine [1]. It focuses on the development of engineered nano-scale (1100 nm) materials, structures and devices for better diagnostics and highly specific medical intervention in curing disease or repairing damaged tissues. As a basis for nanomedicine, nanotechnology is the science, engineering, and technology related to the understanding and control of matter at the nano-scale, and the development of materials, devices, and systems that have novel properties and functions due to their nano-scale dimensions or components. Nanotechnology also provides new abilities to measure, control and manipulate matter (including soft matter) at the nano-scale what was unthinkable with conventional tools. Owing to the size-compatibility of nano-scale structures with proteins and nucleic acids in living cells, nanomedicine approaches have the potential to provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention, thus revolutionizing medicine. Over the last ten years or so, significant efforts have been made in the US, China, Europe and elsewhere to develop nanomedicine. For example, the US National Institutes of Health has developed a nanomedicine centers network, and invested a significant amount of research funding to nanomedicine development. Just in FY 2009 (Oct. 1, 2008Sept. 30, 2009, the total NIH funding in nanotechnology/ nanoscience projects was more than 410 million US dollars. SPECIAL TOPIC

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“…Attaching ligands (e.g. antibodies, nanobodies, and peptides) to the nanoparticles can allow better distribution in the vascular bed of the lesion and increase their internalization by target endothelial cells [218,219]. For example, αvβ3 integrin-targeted delivery of an anti-angiogenic gene has been shown to selectively increase apoptosis of tumor endothelial cells, which subsequently led to tumor cell apoptosis and regression of primary and metastatic tumors [220].…”

Section: Enhanced Microvascular Permeabilitymentioning

confidence: 99%

Targeted therapeutics in inflammatory atherosclerosis

Alaarg¹

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Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging

Abstract: kinetic modeling ͉ multimodality imaging ͉ targeted delivery ͉ tumor uptake

Cited by 743 publications

References 27 publications

Gene therapy progress and prospects: synthetic polymer-based systems

Gene therapy progress and prospects: synthetic polymer-based systems

Engineering imaging probes and molecular machines for nanomedicine

Targeted therapeutics in inflammatory atherosclerosis

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