Kevin S. Chu

University of North Carolina at Chapel Hill

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Joseph M. DeSimone

Stanford University

Charles J. Bowerman

University of North Carolina at Chapel Hill

J. Christopher Luft

University of North Carolina at Chapel Hill

Mary E. Napier

CURE International UK

Sherry Y. Wu

University of Queensland

Anil K. Sood

The University of Texas MD Anderson Cancer Center

Kshipra M. Gharpure

The University of Texas MD Anderson Cancer Center

Rajesha Rupaimoole

The University of Texas MD Anderson Cancer Center

Gabriel Lopez‐Berestein

The University of Texas MD Anderson Cancer Center

Takahito Miyake

Gifu University Hospital

Cooperative Institutions

University of North Carolina at Chapel Hill

UNC Lineberger Comprehensive Cancer Center

Environmental Protection Agency

Research Triangle Park Foundation

The University of Texas MD Anderson Cancer Center

California Institute of Technology

Segeberger Kliniken

University of North Carolina Health Care

University of Iowa

North Carolina State University

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Supplementary Materials and Methods and Supplementary Figure Legends from Metronomic Docetaxel in PRINT Nanoparticles and EZH2 Silencing Have Synergistic Antitumor Effect in Ovarian Cancer

Kshipra M. Gharpure Kevin S. Chu Charles J. Bowerman Takahito Miyake Sunila Pradeep

PDF - 78K, Supplementary methods and legends for supplementary figures.

10.1158/1535-7163.22499899

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Preparation and initial characterization of biodegradable particles containing gadolinium-DTPA contrast agent for enhanced MRI

Proceedings of the National Academy of Sciences (2008)

Amber L. Doiron Kevin S. Chu Adeel Ali Lisa Brannon‐Peppas

Accurate imaging of atherosclerosis is a growing necessity for timely treatment of the disease. Magnetic resonance imaging (MRI) is a promising technique for plaque imaging. The goal of this study was to create polymeric particles of a small size with high loading of diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) and demonstrate their usefulness for MRI. A water-in-oil-in-oil double emulsion solvent evaporation technique was used to encapsulate the MRI agent in a poly(lactide-co-glycolide) (PLGA) or polylactide-poly(ethylene glycol) (PLA-PEG) particle for the purpose of concentrating the agent at an imaging site. PLGA particles with two separate average sizes of 1.83 microm and 920 nm, and PLA-PEG particles with a mean diameter of 952 nm were created. Loading of up to 30 wt % Gd-DTPA was achieved, and in vitro release occurred over 5 h. PLGA particles had highly negative zeta potentials, whereas the particles incorporating PEG had zeta potentials closer to neutral. Cytotoxicity of the particles on human umbilical vein endothelial cells (HUVEC) was shown to be minimal. The ability of the polymeric contrast agent formulation to create contrast was similar to that of Gd-DTPA alone. These results demonstrate the possible utility of the contrast agent-loaded polymeric particles for plaque detection with MRI.

PLGA

Zeta potential

MRI contrast agent

Gadodiamide

10.1073/pnas.0710205105

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Citations (52)

Formation of Light Absorbing Secondary Organic Aerosol from Reactive Uptake of Isoprene Epoxydiols

Kevin S. Chu

Isoprene

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Metronomic Docetaxel in PRINT Nanoparticles and EZH2 Silencing Have Synergistic Antitumor Effect in Ovarian Cancer

Molecular Cancer Therapeutics (2014)

Kshipra M. Gharpure Kevin S. Chu Charles J. Bowerman Takahito Miyake Sunila Pradeep

The purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic experiments were conducted in well-established orthotopic mouse models of epithelial ovarian cancer. Antitumor effects were determined on the basis of reduction in mean tumor weight and number of metastatic tumor nodules in the animals. The tumor tissues from these in vivo studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase 3), and microvessel density (CD31). The lowest dose of metronomic regimen (0.5 mg/kg) resulted in significant reduction in tumor growth. The combination of PLGA-PRINT-docetaxel and CH-mEZH2 siRNA showed significant antitumor effects in the HeyA8 and SKOV3ip1 tumor models (P < 0.05). Individual as well as combination therapies showed significant antiangiogenic, antiproliferative, and proapoptotic effects, and combination therapy had additive effects. Metronomic delivery of PLGA-PRINT-docetaxel combined with CH-mEZH2 siRNA has significant antitumor activity in preclinical models of ovarian cancer.

10.1158/1535-7163.mct-13-0930

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Citations (30)

Data from Metronomic Docetaxel in PRINT Nanoparticles and EZH2 Silencing Have Synergistic Antitumor Effect in Ovarian Cancer

Kshipra M. Gharpure Kevin S. Chu Charles J. Bowerman Takahito Miyake Sunila Pradeep

<div>AbstractThe purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic experiments were conducted in well-established orthotopic mouse models of epithelial ovarian cancer. Antitumor effects were determined on the basis of reduction in mean tumor weight and number of metastatic tumor nodules in the animals. The tumor tissues from these in vivo studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase 3), and microvessel density (CD31). The lowest dose of metronomic regimen (0.5 mg/kg) resulted in significant reduction in tumor growth. The combination of PLGA-PRINT-docetaxel and CH-mEZH2 siRNA showed significant antitumor effects in the HeyA8 and SKOV3ip1 tumor models (P < 0.05). Individual as well as combination therapies showed significant antiangiogenic, antiproliferative, and proapoptotic effects, and combination therapy had additive effects. Metronomic delivery of PLGA-PRINT-docetaxel combined with CH-mEZH2 siRNA has significant antitumor activity in preclinical models of ovarian cancer. Mol Cancer Ther; 13(7); 1750–7. ©2014 AACR.</div>

Ovarian tumor

10.1158/1535-7163.c.6536302

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A versatile acid-labile linker for antibody–drug conjugates

MedChemComm (2014)

Mathew C. Finniss Kevin S. Chu Charles J. Bowerman J. Christopher Luft Zishan A. Haroon

Silyl ether chemistry was used as the linker for an antibody drug conjugate to release a chemotherapeutic at low pH.

Linker

Conjugate

Antibody-drug conjugate

Silyl ether

10.1039/c4md00150h

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Citations (12)

PRINT® nanoparticle parameters to improve docetaxel PK/PD

Kevin S. Chu

Source

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Constraining condensed-phase formation kinetics of secondary organic aerosol components from isoprene epoxydiols

Atmospheric chemistry and physics (2016)

Theran P. Riedel Ying‐Hsuan Lin Z. Zhang Kevin S. Chu Joel A. Thornton

Abstract. Isomeric epoxydiols from isoprene photooxidation (IEPOX) have been shown to produce substantial amounts of secondary organic aerosol (SOA) mass and are therefore considered a major isoprene-derived SOA precursor. Heterogeneous reactions of IEPOX on atmospheric aerosols form various aerosol-phase components or "tracers" that contribute to the SOA mass burden. A limited number of the reaction rate constants for these acid-catalyzed aqueous-phase tracer formation reactions have been constrained through bulk laboratory measurements. We have designed a chemical box model with multiple experimental constraints to explicitly simulate gas- and aqueous-phase reactions during chamber experiments of SOA growth from IEPOX uptake onto acidic sulfate aerosol. The model is constrained by measurements of the IEPOX reactive uptake coefficient, IEPOX and aerosol chamber wall losses, chamber-measured aerosol mass and surface area concentrations, aerosol thermodynamic model calculations, and offline filter-based measurements of SOA tracers. By requiring the model output to match the SOA growth and offline filter measurements collected during the chamber experiments, we derive estimates of the tracer formation reaction rate constants that have not yet been measured or estimated for bulk solutions.

Isoprene

TRACER

Sulfate aerosol

Aqueous two-phase system

Mass concentration (chemistry)

10.5194/acp-16-1245-2016

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Citations (55)

The Coriolis Force and Magnetic Field Effects on Arctic and Antarctic Atmospheric Kinetics and their Implication in Ozone Depletion

APS Ohio Sections Spring Meeting Abstracts (1997)

Kevin S. Chu J. J. Lagatta Jane Wilson B. L. Richards

Ozone Depletion

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Particle Replication in Nonwetting Templates Nanoparticles with Tumor Selective Alkyl Silyl Ether Docetaxel Prodrug Reduces Toxicity

Nano Letters (2014)

Kevin S. Chu Mathew C. Finniss Allison N. Schorzman Jennifer L. Kuijer J. Christopher Luft

Delivery systems designed to have triggered release after passively targeting the tumor may improve small molecule chemotherapeutic delivery. Particle replication in nonwetting templates was used to prepare nanoparticles to passively target solid tumors in an A549 subcutaneous xenograft model. An acid labile prodrug was delivered to minimize systemic free docetaxel concentrations and improve tolerability without compromising efficacy.

Silyl ether

Template

10.1021/nl4046558

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Citations (45)