Softer Zwitterionic Nanogels for Longer Circulation and Lower Splenic Accumulation

Zhang, Lei; Cao, Zhiqiang; Li, Yuting; Ella-Menye, Jean Rene; Bai, Tao; Jiang, Shaoyi

doi:10.1021/nn301159a

Cited by 220 publications

(226 citation statements)

References 26 publications

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“…This phenomenon is closely related to material hydration and nonfouling character. As a well-known class of ultralow fouling materials, zwitterionic polymers have indeed been used to extend the circulation lifetime of nanoparticles (32)(33)(34). Apart from material properties, recent research has shown surface coverage density to be another important factor affecting particle uptake by immune cells and in vivo circulation behavior (35).…”

Section: Resultsmentioning

confidence: 99%

Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity

Zhang

Sun

Tsao

et al. 2015

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

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247

187

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Advances in protein therapy are hindered by the poor stability, inadequate pharmacokinetic (PK) profiles, and immunogenicity of many therapeutic proteins. Polyethylene glycol conjugation (PEGylation) is the most successful strategy to date to overcome these shortcomings, and more than 10 PEGylated proteins have been brought to market. However, anti-PEG antibodies induced by treatment raise serious concerns about the future of PEGylated therapeutics. Here, we demonstrate a zwitterionic polymer network encapsulation technology that effectively enhances protein stability and PK while mitigating the immune response. Uricase modified with a comprehensive zwitterionic polycarboxybetaine (PCB) network exhibited exceptional stability and a greatly prolonged circulation half-life. More importantly, the PK behavior was unchanged, and neither anti-uricase nor anti-PCB antibodies were detected after three weekly injections in a rat model. This technology is applicable to a variety of proteins and unlocks the possibility of adopting highly immunogenic proteins for therapeutic or protective applications.protein delivery | immune response | zwitterionic polymer | hydrogel | nanomedicine

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Section: Resultsmentioning

confidence: 99%

Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity

Zhang

Sun

Tsao

et al. 2015

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

Self Cite

247

187

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“…Globular SCNPs, with a tunable degree of compactness, emerge as a new class of soft colloids bridging the gap between linear polymers and hard colloids. As a consequence they are a very promising, experimentally realisable system for getting insight into the mechanisms of diffusion of soft nano-objects in crowded environments (as expected for nanocarriers in biological habitat) 19,20 , and to draw new strategies for tailoring the rheological properties of polymerbased nanomaterials 21 . The article is organized as follows.…”

Section: Introductionmentioning

confidence: 99%

Tunable slow dynamics in a new class of soft colloids

et al. 2016

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By means of extensive simulations, we investigate concentrated solutions of globular single-chain nanoparticles (SCNPs), an emergent class of synthetic soft nano-objects. By increasing the concentration, the SCNPs show a reentrant behaviour in their structural and dynamical correlations, as well as a soft caging regime and weak dynamic heterogeneity. The latter is confirmed by validation of the Stokes-Einstein relation up to concentrations far beyond the overlap density. Therefore SCNPs arise as a new class of soft colloids, exhibiting slow dynamics and actualizing in a real system structural and dynamical anomalies proposed by models of ultrasoft particles. Quantitative differences in the dynamical behaviour depend on the SCNP deformability, which can be tuned through the degree of internal cross-linking.

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“…Shaoyi Jiang's lab reached similar conclusions in their investigations of the modulus of long-circulating zwitterionic spherical nanoparticles. Spherical particles (d = 250 nm) with a range of cross-link densities were fabricated and were passed through 220 nm porous membranes [41]. While all the "soft" particles were able to pass through the filter, the majority of the "hard" particles (with the highest crosslink densities) were stopped by the filter [41].…”

Section: Modulus/mechanical Propertiesmentioning

confidence: 99%

“…Spherical particles (d = 250 nm) with a range of cross-link densities were fabricated and were passed through 220 nm porous membranes [41]. While all the "soft" particles were able to pass through the filter, the majority of the "hard" particles (with the highest crosslink densities) were stopped by the filter [41]. These trends were also predictive of in vivo particle behavior.…”

Section: Modulus/mechanical Propertiesmentioning

confidence: 99%

“…These trends were also predictive of in vivo particle behavior. As the cross-linker density of the particle was decreased, splenic accumulation was minimized, resulting in extended circulation persistence [41]. With a better understanding of the relevant particle parameters necessary for extending particle circulation, the focus shifts to drug loading and release.…”

Section: Modulus/mechanical Propertiesmentioning

confidence: 99%

See 1 more Smart Citation

Calibration-Quality Cancer Nanotherapeutics

Perry

Kai

Reuter

et al. 2015

Cancer Treatment and Research

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Nanoparticle properties such as size, shape, deformability, and surface chemistry all play a role in nanomedicine drug delivery in cancer. While many studies address the behavior of particle systems in a biological setting, revealing how these properties work together presents unique challenges on the nanoscale. "Calibration-quality" control over such properties is needed to draw adequate conclusions that are independent of parameter variability. Furthermore, active targeting and drug loading strategies introduce even greater complexities via their potential to alter particle pharmacokinetics. Ultimately, the investigation and optimization of particle properties should be carried out in the appropriate preclinical tumor model. In doing so, translational efficacy improves as clinical tumor properties increase. Looking forward, the field of nanomedicine will continue to have significant clinical impacts as the capabilities of nanoparticulate drug delivery are further enhanced.

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Softer Zwitterionic Nanogels for Longer Circulation and Lower Splenic Accumulation

Cited by 220 publications

References 26 publications

Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity

Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity

Tunable slow dynamics in a new class of soft colloids

Calibration-Quality Cancer Nanotherapeutics

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