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TRACK 2 TRACK 2 Technical Program

provide leverage for applying forces directly to intracellular organelles. In microenvironment and for its cytotoxicity. The data showed that Bromelain
HUVECs cultured statically, an external magnetic field could induce redistri- increased the affinity of the particles for the cellular membrane as well as
bution of lysosomes containing MNPs and the formation of actin stress fibers for tumor extracellular matrix. Further experiments were focused on deter-
along the field gradient. Here we further examined whether vascular perme- mining the activity of Bromelain modified particles in digesting commercial
ability could be controlled using intracellular magnetic force. It is known that tumor extracellular matrix matrigel, showing that at T and pH different from
in endothelial cells, a portion of actin filaments are connected to VE-cad- physiological conditions the bioactivity of this surface modification is affect-
herin, a key component of adherens junctions that mediate the paracellular ed. Compared to uncoated nanoparticles, Bromelain modified particles in-
transport pathway of vascular endothelium. Reorganization of actin filaments creased particles diffusion in vivo in a murine model of syngeneic orthotopic
can disrupt endothelial adherens junctions and increase vascular permea- breast cancer where the modified particle penetrated deeper in the tumor
bility. In light of these evidences, we designed magnetic field through nu- parenchyma and increased their residence time in the lesion. In conclusion,
merical simulations, and investigated magnetic force induced the structural we showed that Bromelain efficiently increased the penetration of synthetic
and functional changes of vascular endothelium in vitro in endothelialized nanoparticles in the tumor parenchyma. Further studies will be performed to
microfluidic channels and in vivo in a mouse model. understand the impact of this procedure on tumor biology. In fact, while our
work support the hypothesis that the use of proteolytic agents can favor the
Our studies demonstrated that in endothelialized microfluidic channels diffusion of nanoparticles in tumor parenchyma, the loss of tumor ECM can
cultured with flow, the uptake of MNPs by vascular endothelium could be favor cancer cells mobility and metastatic progression, therefore more inves-
enhanced with a magnetic field. Subsequently, an intracellular magnetic tigation are currently undergoing.
force perpendicular to the flow direction temporarily disrupted actin stress
fibers and endothelial adherens junctions formed under the physiological 5:10pm Cancer Targeting Nanoparticle Exhibit Minimal Interac-
flow condition. Furthermore, in an in vivo study, we showed that MNPs could tion With Cancer Cells In Vivo
be targeted to local vasculature using an external magnetic field. After that,
the changes in local vascular permeability was examined using ICG angiog- Technical Presentation. NEMB2016-5914
raphy. ICG injected intravenously showed increased accumulation in tissues
treated magnetically.
Qin Dai, Ding Ding, Stefan Wilhelm, Warren C.W. Chan, Universi-
In summary, this study offers a promising approach for remote control of ty of Toronto, Toronto, ON, Canada
vascular permeability by disrupting endothelial adherens junctions with
intracellular magnetic force. It can be used to overcome the intrinsic hetero- Tumor targeting using nanoparticles is an exciting and emerging field. In
geneity in pathological angiogenesis and provide entry for drug molecules particular, cellular targeting using nanoparticles garnered interest due to
in diseases that do not involves changes in local vascular permeability or up its proposed ability to recognize overexpressed receptors on malignant
regulation of disease markers. At last, this approach extends targeted de- cancer cell surfaces. The purpose behind this approach is to increase
livery to a broad range of therapeutic agents that can not be conjugated or specific destruction of cancer cell to enhance therapeutic effect, while re-
encapsulated using current fabrication techniques. ducing non-specific interactions that could damper its intended purpose.
This is no easy task, since only <1% of the injected nanoparticles reach the
4:50pm A Proteolytic Surface Modification Enhances Nanopar- tumor and even less are likely to interact with the cells. Therefore there is
ticles Diffusion In Cancer Stroma a dire need to provide systematic evidences that quantify the efficiency of
nanoparticle targeting to malignant cancer cells, as well as nanoparticle
interactions with its surrounding microenvironment. Here we show that
Technical Presentation. NEMB2016-6057 >>90% of the ErbB2 (epidermal growth factor receptor 2) cancer targeting
nanoparticles within the tumor microenvironment are extracellular matrix
Alessandro Parodi, Houston Methodist Research Institute, Hous- associated and unable to interact with cells. By using flow cytometry anal-
ton, TX, United States, Francesca Taraballi, Houston Methodist Re- ysis on tumor single cell suspension, we showed that tumor associated
search Inst., Houston, TX, United States, Claudia Corbo, Jonhatan macrophage exhibit 3 fold difference in interaction with 50nm ErbB2 can-
Otto Martinez, Houston Methodist Research Institute, Houston, TX, cer targeting nanoparticles compared to SKOV-3 cancer cells, suggesting
United States, Ennio Tasciotti, The Methodist Hospital Research that the nanoparticles are not targeting cancer cells as intended. Further-
Institute, Houston, TX, United States more, nanoparticle per tumor associated macrophage is significantly high-
er than that per cancer cell. In comparison, 15 and 100nm nanoparticles
exhibited 5 fold less interaction with cells in the tumor. These data collec-
Tumor extracellular matrix (ECM) represents a major biological barrier tively suggest that there’s a size dependence on nanoparticle interaction
affecting the proper diffusion of many therapeutics and drug delivery sys- with cells in vivo, however this interaction is mainly dominated by tumor
tems in the cancer parenchyma. This biological barrier limits the efficacy of
promising therapeutic approaches including the delivery of siRNA or agents associated macrophage nanoparticle interaction despite the presence
of cancer targeting surface ligands. This study provides a systematic
intended for thermoablation. After extravasation typical nanotherapeutics understanding and quantitative outlook at in vivo nanoparticle-cell inter-
are stucked in the sub-endothelial space and are unable to reach the poorly action within the tumor microenvironment, and calls for action for future
vascularized and anoxic regions deep within the cancer lesion. Tumor ECM quantification in cancer-nanoparticle investigations. Tumor associated
is a well-characterized net of proteins and biomolecules exploited by the
cells to sustain their growth and movement. The remodeling of tumor ECM macrophage targeting nanoparticles should be investigated in detail as an
alternative cancer treatment strategy.
is well-known to be naturally driven by the action of proteases that affect its
integrity through specific proteolytic enzymatic action. Bromelain is a pro-
teolipid complex that can be easily purified from the stem the of pineapple 5:30pm MRI-Guided Laser Ablation
plant and is commercialized as dietary supplement, and approved by FDA
to mitigate the inflammatory processes that accompany post-orthopedic sur- Technical Presentation. NEMB2016-6164
gery. Its role in cancer disease was recently tested in pre-clinical studies and
literature showed that Bromelain can contribute in favoring cancer cell apop- R. Jason Stafford, The University of Texas MD Anderson Cancer
tosis. Here we investigated the benefits of Bromelain surface modification to Center, Department of Physics, Houston, TX, United States
increase the diffusion of synthetic particles in the tumor ECM by exploiting
its proteolytic bioactivity. Interstitial laser ablation systems aim to coagulate a localized tissue volume.
Modern clinical systems utilize compact, high power, solid state laser sourc-
Bromelain was conjugated to the surface of mesoporous silica nanoparticles es which incorporate cooled applicators in order treat larger volumes of tis-
through an APTES chemical linker. The system was characterized in vitro sue. Additionally, systems operate in the near infrared part of the spectrum 23
and in vivo for its ability to be internalized by different cells of the tumor and therefore are synergistic emerging nanophotonic applications which