Efficient renal clearance of DNA tetrahedron nanoparticles enables quantitative evaluation of kidney function

Jiang, Dawei; Im, Hyung‐Jun; Boleyn, Madeline E; England, Christopher G.; Ni, Dalong; Liu, Kang; Engle, Jonathan W.; Huang, Peng; Lan, Xiaoli; Cai, Weibo

doi:10.1007/s12274-019-2271-5

Cited by 40 publications

(32 citation statements)

References 36 publications

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“…A highly interesting property of DNA nanostructures is that they have been reported to not accumulate in the liver, and can be engineered to be small (~20 nm), meaning extrahepatic delivery is possible. However, further reducing the size of DNA nanostructures without additional functionalization will likely result in enhanced renal filtration, and overall lower bioavailability 275,277 .…”

Section: Spherical Nucleic Acidsmentioning

confidence: 99%

Advances in oligonucleotide drug delivery

Roberts

Langer

Wood

2020

Nat Rev Drug Discov

1,367

1,222

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Oligonucleotides can be used to modulate gene expression via a range of processes including RNAi, target degradation by RNase H-mediated cleavage, splicing modulation, non-coding RNA inhibition, gene activation and programmed gene editing. As such, these molecules have potential therapeutic applications for myriad indications, with several oligonucleotide drugs recently gaining approval. However, despite recent technological advances, achieving efficient oligonucleotide delivery, particularly to extrahepatic tissues, remains a major translational limitation. Here, we provide an overview of oligonucleotide-based drug platforms, focusing on key approaches-including chemical modification, bioconjugation and the use of nanocarriers-which aim to address the delivery challenge.

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Section: Spherical Nucleic Acidsmentioning

confidence: 99%

Advances in oligonucleotide drug delivery

Roberts

Langer

Wood

2020

Nat Rev Drug Discov

1,367

1,222

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“…Jiang et al . have investigated the biological fate of a wireframe tetrahedral nanostructure by radiolabeling it with Cu‐64 for positron‐emission tomography (PET) imaging.…”

Section: Metabolism and Eliminationmentioning

confidence: 99%

Section: Metabolism and Eliminationmentioning

confidence: 99%

Progress Toward Absorption, Distribution, Metabolism, Elimination, and Toxicity of DNA Nanostructures

Messaoudi

Greschner

Gauthier

2019

Advanced Therapeutics

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DNA nanostructures are perfectly defined nanomaterials, and their shape/structure/surface chemistry (e.g., appended ligands) can be conveniently modulated by designing the sequence of their constituent DNA strands. No other natural or synthetic drug delivery system offers such predictability or modularity. As such, DNA nanostructures may provide exciting and potentially new opportunities for delivering drugs to diseased cell populations, or to specific sub-cellular compartments. To date, however, most studies have been performed in cell culture and only recently has the field advanced to in vivo testing. Considering how rapidly the field is evolving, this Progress Report surveys available studies involving the testing of DNA nanostructures in vivo, in an effort to elucidate trends and provide guidelines for future developments. This contribution presents the current progress toward characterizing the absorption, distribution, metabolism, elimination, and toxicity of DNA nanostructures.

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“…Pharmacokinetic modeling is used to quantify kinetic behaviors from pharmacokinetic curves [20][21][22][23][24][25]. Compartmental modeling has been routinely applied to derive kinetic parameters in previous studies, facilitating a better understanding of the information contained in the dynamic in vivo imaging data [26].…”

Section: Introductionmentioning

confidence: 99%

Mixing Matrix-corrected Whole-body Pharmacokinetic Modeling Using Longitudinal Micro-computed Tomography and Fluorescence-mediated Tomography

et al. 2021

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Purpose Pharmacokinetic modeling can be applied to quantify the kinetics of fluorescently labeled compounds using longitudinal micro-computed tomography and fluorescence-mediated tomography (μCT-FMT). However, fluorescence blurring from neighboring organs or tissues and the vasculature within tissues impede the accuracy in the estimation of kinetic parameters. Contributions of elimination and retention activities of fluorescent probes inside the kidneys and liver can be hard to distinguish by a kinetic model. This study proposes a deconvolution approach using a mixing matrix to model fluorescence contributions to improve whole-body pharmacokinetic modeling. Procedures In the kinetic model, a mixing matrix was applied to unmix the fluorescence blurring from neighboring tissues and blood vessels and unmix the fluorescence contributions of elimination and retention in the kidney and liver compartments. Accordingly, the kinetic parameters of the hepatobiliary and renal elimination routes and five major retention sites (the kidneys, liver, bone, spleen, and lung) were investigated in simulations and in an in vivo study. In the latter, the pharmacokinetics of four fluorescently labeled compounds (indocyanine green (ICG), HITC-iodide-microbubbles (MB), Cy7-nanogels (NG), and OsteoSense 750 EX (OS)) were evaluated in BALB/c nude mice. Results In the simulations, the corrected modeling resulted in lower relative errors and stronger linear relationships (slopes close to 1) between the estimated and simulated parameters, compared to the uncorrected modeling. For the in vivo study, MB and NG showed significantly higher hepatic retention rates (P<0.05 and P<0.05, respectively), while OS had smaller renal and hepatic retention rates (P<0.01 and P<0.01, respectively). Additionally, the bone retention rate of OS was significantly higher (P<0.01). Conclusions The mixing matrix correction improves pharmacokinetic modeling and thus enables a more accurate assessment of the biodistribution of fluorescently labeled pharmaceuticals by μCT-FMT.

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Efficient renal clearance of DNA tetrahedron nanoparticles enables quantitative evaluation of kidney function

Cited by 40 publications

References 36 publications

Advances in oligonucleotide drug delivery

Advances in oligonucleotide drug delivery

Progress Toward Absorption, Distribution, Metabolism, Elimination, and Toxicity of DNA Nanostructures

Mixing Matrix-corrected Whole-body Pharmacokinetic Modeling Using Longitudinal Micro-computed Tomography and Fluorescence-mediated Tomography

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