Page 22 - ASME_NEMB_2016_Program

Technical Program TRACK 2

°C/min to avoid devitrifiation. Furthermore, these rates must be sufficiently Session Organizer: Jun Wang, University of Science and Technolo-
uniform to avoid thermal stresses in excess of the yield stress (typically 2 gy of China, Hefei, Anhui, China
MPa) which can crack the tissue. By achieving faster yet sufficiently uniform
rates of cooling and warming, the concentration of the CPA can also be 4:00pm Stem Cell/Nanoparticle Conjugates For Targeted Can-
reduced thereby reducing chemical (i.e. CPA) toxicity on the tissue. Here
we present a new technology that allows ultra-rapid warming rates (~1000 cer Therapy
°C/min), which may allow dramatic improvements in preservation of vitrified
biomaterials. Keynote. NEMB2016-6088

Acknowledgements. Funding from NSF CBET 1336659, the MN Futures Jacob Berlin, City of Hope, Beckman Research Inst., Duarte, CA,
grant and the Kuhrmeyer Chair to JCB and NM are gratefully acknowledged. United States
Manuchehrabadi and Shi contributed equally to the work and are co-first au-
thors. ACC worked as a volunteer high school student researcher in BHMT Targeted drug delivery is a long-standing goal for cancer therapy. Nanopar-
lab UM during summer 2015. Lu and Bischof are joint corresponding authors. ticles have shown promise as platforms for targeted drug delivery, but major
challenges remain for controlling the distribution of nanoparticles within
12:40pm Engineering the Next Generation of Drug-loaded tumors. Neural Stem Cells (NSCs) are appealing candidates for use as carri-
Functionalized Electrospun Poly(caprolactone) Scaffolds for ers for nanoparticles in order to overcome these biodistribution challenges.
Cancer Treatment NSCs have demonstrated inherent tumor tropic properties in invasive and
metastatic tumor models, migrating selectively to invasive tumor foci, pene-
Technical Presentation. NEMB2016-6099 trating hypoxic tumor regions, and even traversing through the blood-brain
barrier to access intracranial tumor foci following intravenous administration.
NSCs do not intrinsically have any anti-tumor efficacy; they must be modi-
Manisha Jassal, Vijay Boominathan, Tracie Ferreira, Sukalyan fied in some way to exploit their tumor targeting abilities. My collaborator,
Sengupta, Sankha Bhowmick, Univ Of Massachusetts-Dartmouth, Dr. Karen Aboody, is a pioneer in genetically altering NSCs to express an
Dartmouth, MA, United States enzyme that will convert a prodrug into the active compound. This approach
was recently evaluated in a first-in-human safety/feasibility clinical trial using
Controlled drug delivery is required to improve the therapeutic efficacy of modified NSCs to treat recurrent gliomas.
the drug and to reduce the potential toxic effects by delivering the drug at
a rate governed by the physiological need of the site of action. Developing As NSC-based therapy moves into the clinic, there is an opportunity to de-
new scaffolds to deliver drug in a controlled manner to a tumor is an im- velop complementary techniques to enable NSCs to destroy tumors. The
portant task and translating the performance of these scaffolds to an in-vivo combination of NSCs and nanoparticles offers the potential of a general
model is the next logical step. The tumor environment is different than the drug targeting system. We have demonstrated that NSCs can either be
normal healthy tissue in terms of blood flow, oxygen and nutrient supply, modified to bear nanoparticles on their surface or can internalize them. The
tissue oxygen and pH distribution. Similarly, the interstitial fluid flow (fluid nanoparticles can release drugs or used for photothermal ablation. In all cas-
found in stroma of tissue) is also different in a tumor than in a healthy tissue. es, the NSCs remained viable and targeted the delivery of the nanoparticles
In cancer, vasculature irregularities lead to increased flow rates through the to tumors in vivo, enhancing the therapeutic efficacy of the nanoparticles.
tissue. The drug delivery from a scaffold implanted near the tumor would
depend on this fluid flow, if the drug is physically/ionically bound to the scaf- 4:30pm Magnetic enhancement of vascular permeability for
fold. In the current study, poly(caprolactone) (PCL) fibers were fabricated by targeted drug delivery
electrospinning, followed by hydrolysis to introduce functional groups on the
fiber surface. These functional groups (-COOH) were then utilized to ionically
bind doxorubicin hydrochloride (DOX), an FDA approved anticancer drug. Technical Presentation. NEMB2016-5974
The scaffolds exhibit differences in release behavior between a very narrow
window of pH 6.0 and pH 7.2 that would have a wide variety of applications Sheng Tong, Rice University, Houston, TX, United States, Yongzhi
due to acidic extracellular pH of most tumors. Qiu, Georgia Institute of Technology and Emory University, Atlanta,
GA, United States, Linlin Zhang, Gang Bao, Rice University, Hous-
The purpose of this study is to determine the usefulness of these DOX-load- ton, TX, United States
ed electrospun PCL scaffolds in an in-vivo situation. In here, a continuous
flow system was designed using a syringe pump and flow rates that corre- Vascular endothelium presents a major transport barrier to therapeutic
spond to interstitial fluid flow rates experienced in tumors. The drug release agents administrated systemically. In normal vasculature, endothelial cells
from scaffolds was studied with the continuous flow system with media form a monolayer via cell-cell junctions that only allow selective extravasa-
maintained at different pH and a differential drug release was obtained tion of solutes, ions and small molecules, while others have to pass through
under these conditions. Then, a composite scaffold system consisting of vascular endothelium via less effective transcytosis. Current drug delivery
drug-loaded electrospun scaffolds and hydrogels that release acid were strategies often involve conjugation or encapsulation of therapeutic agents
subjected to the same continuous flow system in order to establish a control with macromolecules or nanoparticles. Transvascular transport of these drug
on the drug release profile by utilizing the pH-dependent DOX release from carriers thus relies on leaky vessels arising from pathological angiogenesis,
functionalized PCL fibers. Further, the effect of DOX being released from e.g. tumor angiogenesis. However, drug delivery through leaky vasculature
the electrospun scaffolds was studied on human embryonic kidney cells is rarely effective due to the heterogeneity in tumor vasculature. Developing
under different pH environment. The results corroborate the pH-dependent proactive delivery strategies independent of pathophysiological conditions
release of electrostatically bound DOX that can be exploited for site-specif- are paramount for adequate and uniform intratumoral distribution of ther-
ic targeted controlled DOX delivery. In the end, the drug-loaded scaffolds apeutic agents. Here we present an engineering approach of controlling
were implanted in an actual animal model (zebrafish) to study the drug re- vascular permeability via magnetic iron oxide nanoparticles (MNPs) and a
lease and determine the applicability of these scaffolds in real-life scenario. well-designed magnetic field for enhanced targeted drug delivery.
Over the past few years, MNPs have emerged as promising drug carriers
2-2 for their potentials in image-guided drug delivery, magnetic drug targeting
NANOPARTICLE-BIOLOGICAL INTERACTIONS and hyperthermia. As nano-sized magnets, MNPs experience a force along
22 the gradient of magnetic field. We have shown that magnetic force could
Bexar/Travis 4:00pm - 5:30pm enhance the endocytosis of MNPs by human umbilical vein endothelial
cells (HUVECs) without affecting cell viability. Importantly, internalized MNPs