Influence of Polymer Size on Uptake and Cytotoxicity of Doxorubicin-Loaded DNA–PEG Conjugates

Purdie, Laura; Alexander, Cameron; Spain, Sebastian G.; Magnusson, Johannes P.

doi:10.1021/acs.bioconjchem.6b00085

Cited by 10 publications

(18 citation statements)

References 31 publications

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“…To address the susceptibility of the particles to Ostwald ripening, we assayed for distribution of the hydrodynamic particle size after 7 months of storage at 4 °C in the dark [24,25]. There were no profound changes in the mean hydrodynamic particle size distribution of stored particles in comparison to freshly prepared materials (Figure 1 and Figure 2).…”

Section: Resultsmentioning

confidence: 99%

An Abraded Surface of Doxorubicin-Loaded Surfactant-Containing Drug Delivery Systems Effectively Reduces the Survival of Carcinoma Cells

et al. 2016

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An effective antitumor remedy is yet to be developed. All previous approaches for a targeted delivery of anticancer medicine have relied on trial and error. The goal of this study was to use structural insights gained from the study of delivery systems and malignant cells to provide for a systematic approach to the development of next-generation drugs. We used doxorubicin (Dox) liposomal formulations. We assayed for cytotoxicity via the electrical current exclusion method. Dialysis of the samples yielded information about their drug release profiles. Information about the surface of the delivery systems was obtained through synchrotron small-angle X-ray scattering (SAXS) measurements. SAXS measurements revealed that Dox-loading yielded an abraded surface of our Dox liposomal formulation containing soybean oil, which also correlated with an effective reduction of the survival of carcinoma cells. Furthermore, a dialysis assay revealed that a higher burst of Dox was released from soybean oil-containing preparations within the first five hours. We conclude from our results that an abraded surface of Dox-loaded drug delivery system increases their efficacy. The apparent match between surface geometry of drug delivery systems and target cells is suggested as a steppingstone for refined development of drug delivery systems. This is the first study to provide a systematic approach to developing next-generation drug carrier systems using structural insights to guide the development of next-generation drug delivery systems with increased efficacy and reduced side effects.

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Section: Resultsmentioning

confidence: 99%

An Abraded Surface of Doxorubicin-Loaded Surfactant-Containing Drug Delivery Systems Effectively Reduces the Survival of Carcinoma Cells

et al. 2016

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“…Administration via other routes has essentially been exploited to achieve a local effect, and rapid uptake by cells (within minutes) at the site of administration has generally been observed (and desired). These results suggest that reaching the systemic circulation by non‐vascular administration, should this be desired in the future, will require that additional modifications be made to the DNA nanostructure, such as by, for example, PEGylation or formulation into another carrier, to prevent or delay cellular uptake at the site of administration.…”

Section: Route Of Administration and Absorptionmentioning

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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“…Polymeric delivery vehicles have been employed to improve both the solubility and bioavailability of drugs to improve their efficacy and/or diminish their toxicity. 20,21 These vehicles can improve the retention of the drug in the human body due to reduced renal clearance. [22][23][24] Targeting is also possible through incorporation of ligands that promote active transport into specific cells via receptor-mediated endocytosis.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the anionic hydroxypropyl-β-cyclodextrin:poly(decamethylenephosphate) polyrotaxane and evaluation of its cholesterol efflux potential in Niemann–Pick C1 cells

et al. 2019

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Influence of Polymer Size on Uptake and Cytotoxicity of Doxorubicin-Loaded DNA–PEG Conjugates

Abstract: (2016) Influence of polymer size on uptake and cytotoxicity of doxorubicin-loaded DNA-PEG conjugates. Bioconjugate Chemistry, 27 (5).

Cited by 10 publications

References 31 publications

An Abraded Surface of Doxorubicin-Loaded Surfactant-Containing Drug Delivery Systems Effectively Reduces the Survival of Carcinoma Cells

An Abraded Surface of Doxorubicin-Loaded Surfactant-Containing Drug Delivery Systems Effectively Reduces the Survival of Carcinoma Cells

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

Synthesis of the anionic hydroxypropyl-β-cyclodextrin:poly(decamethylenephosphate) polyrotaxane and evaluation of its cholesterol efflux potential in Niemann–Pick C1 cells

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