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Zwitterionic Janus Dendrimer with distinct functional disparity for enhanced protein delivery.

08:00 EDT 31st May 2019 | BioPortfolio

Summary of "Zwitterionic Janus Dendrimer with distinct functional disparity for enhanced protein delivery."

The development of a facile protein delivery vehicle is challenging and remains an unmet demand for clinical applications. The well-defined structure and functionality of a nanocarrier are highly desirable for the reproducibility and regulatory compliance. Herein, we report for the first time a novel Janus dendrimer (JD) system, comprised of two distinct dendrons with superior protein binding and protein repelling properties, respectively, for efficient spontaneous protein loading and enhanced in vivo protein delivery. Core-forming dendron is tethered with a combination of charged and hydrophobic moieties, which coat protein surface efficiently via the multivalent and synergistic interactions. Zwitterionic peripheries on the counter dendron endow the nanoparticle (<20 nm) with a highly hydrophilic and antifouling surface, which efficiently prevents serum protein adsorption and exchange as demonstrated in biolayer interferometry assay, therefore, reducing premature protein release. Surprisingly, JD nanocarriers containing biomimicking glycerylphosphorylcholine (GPC) surface significantly enhanced the intracellular uptake of protein therapeutics specifically in cancer cells, compared with zwitterionic carboxybetain (CB)-JD and PEGylated nanocarriers. The zwitterionic JD nanocarriers greatly prolonged the in vivo pharmacokinetic profiles of payloads relative to the PEGylated nanocarriers. Janus nanocarrier controlled the in vivo release of insulin and improved the blood sugar control in mice.

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Journal Details

This article was published in the following journal.

Name: Biomaterials
ISSN: 1878-5905
Pages: 119233

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Medical and Biotech [MESH] Definitions

Agents that inhibit JANUS KINASES.

A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.

A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.

An interleukin-21 receptor subunit that combines with the INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT to form a high affinity receptor for interleukin-21. It signals via interaction of its cytoplasmic domain with JANUS KINASES such as JANUS KINASE 1 and JANUS KINASE 3.

A Janus kinase subtype that is predominantly expressed in hematopoietic cell. It is involved in signaling from a broad variety of CYTOKINE RECEPTORS including ones that utilize the INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT.

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