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Technical Program TRACK 5

TRACK 5 NANOMATERIALS DESIGN AND 10:00am Getting the most from droplet microfluidic platforms
MANUFACTURING in nano/bio-materials synthesis
Technical Presentation. NEMB2016-5948
MONDAY, FEBRUARY, 22
Amy Shen, Okinawa Institute of Science and Technology Graduate
University, Okinawa, Japan
5-1
MICRO- AND NANO-MATERIALS DESIGN FOR CONTROLLED Microfluidics has emerged in recent years as a versatile method of manip-
RELEASE ulating fluids at small length-scales, and in particular, for generating and
manipulating micron size droplets with controllable size and functionality. For
example, many research groups developed microfluidics devices for cell en-
Harris 9:30am - 11:00am capsulation, and synthesizing functionalized polymer microspheres and inor-
ganic nanoparticles with precise control over their shapes and sizes. In this
talk, I will showcase droplet microfluidic platforms to highlight their versatility
9:30am Light and magnetic field activated release of antican- and potential applications in nano-materials synthesis.
cer drugs
(a) A droplet microfluidics method to fabricate alginate microspheres while
Keynote. NEMB2016-6162 simultaneously immobilizing anti-Mycobacterium tuberculosis complex IgY
and anti-Escherichia coli IgG antibodies primarily on the porous alginate
Fuyu Tamanoi, UCLA, Los Angeles, CA, United States carriers for specific binding and binding affinity tests. The binding affinity
of antibodies is directly measured by fluorescence intensity of stained tar-
Controlled release of anticancer drugs in response to external stimuli such get bacteria on the microspheres. We demonstrate that the functionalized
as light and magnetic field is one of the major goals of nanoparticle based alginate microspheres yield specificity comparable with an enzyme-linked
drug delivery. When combined with tumor targeting of nanoparticles, this immunosorbent assay. We can easily modify the size and shape of alginate
type of external control could provide precise spatial and temporal control microspheres, and increase the concentration of functionalized alginate mi-
over anticancer drug delivery. This could significantly reduce side effects crospheres to further enhance binding kinetics and enable multiplexing.
associated with current chemotherapy and change the way cancer thera-
py is carried out. We have exploited relative stability of mesoporous silica (b) Cell microencapsulation technology involves immobilization of the cells
nanoparticles (MSNs) to confer mechanisms for controlled release in re- within a polymeric semi-permeable membrane that permits the diffusion of
sponse to external stimul. MSNs are prepared by sol-gel method and the the molecules, such as the influx of oxygen, growth factors and so on for
use of surfactants results in the generation of a material with thousands of cells living, and the outward diffusion of waste products and useful proteins.
pores. We have shown that anticancer drugs can be stored in the pores and Recently, microfluidic techniques have proved useful for cell encapsulation
can be released. Safety and biocompatibility of the material have been eval- by using alginate droplets as the microcapsules. This approach preserves
uated in a number of animal experiments. cell viability as well as monodispersity of the microcapsules. A novel droplet
microfluidics method to image oxygen in single islets (pancreatic cells) for
glucose sensing. Individual islets and a fluorescent oxygen-sensitive dye
To achieve light activated drug release, we took advantage of azobenzene
that changes conformation upon light exposure. Azobenzene is incorporat- were encased within a thin alginate polymer microcapsule for insulin se-
ed into MSNs by lining up the wall of the pores where anticancer drugs are cretion monitoring. The sensing system operated similarly from 2-48 hours
loaded. In addition to azobenzene, we add fluorophore that can capture following encapsulation, and viability and function of the islets were not
energy from two photon light source. The captured energy is then trans- significantly affected by the encapsulation process. This approach should be
ferred to azobenzene causing release of anticancer drugs. Operation of this applicable to other cell types and dyes sensitive to other biologically import-
type of system was demonstrated in aqueous solution as well as in human ant molecules.
breast cancer cells. A slightly different type of light activated release system
uses azobenzene incorporated into nanovalve caps that are placed at the (c) Based on part (b), proof of concept studies of a cryopreserved microcap-
opening of the pores. Use of rotaxane or pseudorotaxane as nanovalves sule-based quality control assays are presented for single islets. Individual
provides an open and close function for anticancer drugs. rat pancreatic islets and fluorescent oxygen-sensitive dye (FOSD) are encap-
For a system that responds to magnetic field, we have used MSNs that sulated in alginate hydrogel microcapsules via a microfluidic device. To test
have iron oxide core. Because of superparamagnetic property of iron oxide, the susceptibility of the microcapsules and the FOSD to cryopreservation,
exposure to oscillating magnetic field results in increase of temperature of the islet microcapsules containing FOSD are cryopreserved and the islet
nanoparticles. We use the heat to open nanovalves that enable to release functionalities (adenosine triphosphate, static insulin release measurement,
of anticancer drugs. Operation of this system was demonstrated in aqueous and oxygen consumption rate) are assessed after freezing and thawing
solution as well as in human cancer cells. In the cell experiment, cells with steps. The cryopreserved islet-capsules with FOSD remain functional after
Doxorubicin containing MSNs taken up are placed in a magnetic coil that encapsulation and freezing/thawing procedures, validating a simple yet
generates oscillating magnetic field. Release of doxorubicin inside the cell reliable individual-islet-based quality control method for the entire islet
was confirmed by red fluorescence of this drug. In addition, cell killing due processing procedure prior to transplantation. This work also demonstrates
to doxorubicin was observed. that the functionality of cryopreserved islets can be improved by introducing
trehalose into the routinely-used cryoprotectant dimethyl sulfoxide. The
functionalized alginate hydrogel microcapsules with embedded FOSD and
The above study was carried out as a long standing collaboration with Dr.
Jeffery Zink (Dept. of Chemistry and Biochemistry, UCLA). The study may optimized cryopreservation protocol presented in this work serve as a ver-
have implications for the design of medical equipment that can carry out satile islet quality assay and offer tremendous promise for tackling existing
therapy in response to light and magnetic field. It may be possible to modify challenges in islet transplantation procedures.
endoscopy to detect tumor and expose to light. In addition, medical equip-
ment to generate magnetic field could be envisioned in the future. Our 10:20am Tailor-made Polyurethane-based Multi-block Nanoma-
development of novel nanoparticles that respond to external stimuli and terials as Drug Delivery Systems
release anticancer drug release may have impact on future clinical settings.
These will be discussed. Technical Presentation. NEMB2016-5992
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