Polyethylene Glycol Backfilling Mitigates the Negative Impact of the Protein Corona on Nanoparticle Cell Targeting

Dai, Qing; Walkey, Carl; Chan, Warren C. W.

doi:10.1002/ange.201309464

Cited by 40 publications

(50 citation statements)

References 34 publications

(17 reference statements)

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“…In contrast, addition of the cDNA strand increases the DNA density, resulting in improved protection. Another important factor is the effect of PEG backfill layer, which blocks enzymatic access to DNA (17,(24)(25)(26)(27). DNA strand that is shorter than the thickness of the PEG layer is protected from protein binding by being fully submersed within the PEG molecules.…”

Section: Resultsmentioning

confidence: 99%

Controlling DNA–nanoparticle serum interactions

Zagorovsky

Chou

Chan

2016

Proc. Natl. Acad. Sci. U.S.A.

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Understanding the interaction of molecularly assembled nanoparticles with physiological fluids is critical to their use for in vivo delivery of drugs and contrast agents. Here, we systematically investigated the factors and mechanisms that govern the degradation of DNA on the nanoparticle surface in serum. We discovered that a higher DNA density, shorter oligonucleotides, and thicker PEG layer increased protection of DNA against serum degradation. Oligonucleotides on the surface of nanoparticles were highly resistant to DNase I endonucleases, and degradation was carried out exclusively by protein-mediated exonuclease cleavage and full-strand desorption. These results enabled the programming of the degradation rates of the DNA-assembled nanoparticle system from 0.1 to 0.7 h −1 and the engineering of superstructures that can release two different preloaded dye molecules with distinct kinetics and half-lives ranging from 3.3 to 9.8 h. This study provides a general framework for investigating the serum stability of DNA-containing nanostructures. The results advance our understanding of engineering principles for designing nanoparticle assemblies with controlled in vivo behavior and present a strategy for storage and multistage release of drugs and contrast agents that can facilitate the diagnosis and treatment of cancer and other diseases.nanoparticle assembly | DNA nanostructures | serum stability | serum resistance | controlled cargo release

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Section: Resultsmentioning

confidence: 99%

Controlling DNA–nanoparticle serum interactions

Zagorovsky

Chou

Chan

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, the in vivo antitumor efficacy of ATB was markedly enhanced without significant toxicity in normal tissues. Previous studies have reported that the affinity of nanocarriers for cells or organs may attribute to their interaction with cell membranes [30][31][32][33][34] . Moreover, this effect is conducive for ATB to play a strong tumor curative effect in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Chitosan reportedly exhibits exceptional adhesion ability with lung cancer cells through H-bonding interaction and biotic stickiness [23][24][25][26] . In addition, Pluronic copolymers, which have a hydrophilic and flexible nature similar to PEG [27][28][29] , are often used to prevent the adsorption of plasma protein, resulting in increased accumulation at the tumor site [30][31][32][33][34] . Thus, we sought to exploit and combine the biotic stickiness of chitosan and the enhanced accumulation effect of PEGylation to generate polymer micelles to promote the affinity and cellular uptake of ATB toward lung tumor cells.…”

Section: Original Articlementioning

confidence: 99%

Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells

et al. 2016

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Acetylthevetin B (ATB), a cardiac glycoside from the seed of Thevetia peruviana (Pers) K Schum (yellow oleander), exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 (CP) micelle encapsulation. Two ATB-loaded CP micelles (ATB-CP1, ATB-CP2) were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40-50 nm, showed a neutral zeta potential, and had acceptable encapsulation efficiency (>90%). Compared to the free ATB (IC 50 =2.94 μmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC 50 values (0.76 and 1.44 μmol/L for ATB-CP1 and ATB-CP2, respectively). After administration of a single dose in mice, the accumulation of ATB-loaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATBloaded CP1 micelles for 21 d showed the smallest tumor volume (one-fourth of that in the control group) and the highest inhibition rate (85.6%) among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, ATB may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects.

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“…Surface passivation reduces both macrophage uptake and increases blood circulation half-life for a variety of nanoparticle types [43][44][45]. In addition, the loss of specificity due to serum protein adsorption and nanoparticle aggregation is also drastically reduced with appropriate passivation of the surface with PEG [37,46]. However, proteins continue to adsorb on the nanoparticle surface even when the nanoparticle surface is decorated with a very dense layer of PEG [43].…”

Section: Surface Passivation Is the Predominant Strategy To Reduce Thmentioning

confidence: 95%

How Nanoparticles Interact with Cancer Cells

Syed

Chan

2015

Cancer Treatment and Research

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There are currently no nanoparticle formulations that optimally target diseased cells in the body. A small percentage of nanoparticles reach these cells and most accumulate in cells of the mononuclear phagocytic system. This chapter explores the interactions between nanoparticles and cells that may explain the causes for off-target accumulation of nanoparticles. A greater understanding of the nanoparticle-cellular interactions will lead to improvements in particle design for improved therapeutic outcome.

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Polyethylene Glycol Backfilling Mitigates the Negative Impact of the Protein Corona on Nanoparticle Cell Targeting

Cited by 40 publications

References 34 publications

Controlling DNA–nanoparticle serum interactions

Controlling DNA–nanoparticle serum interactions

Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells

How Nanoparticles Interact with Cancer Cells

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