Page 73 - ASME_NEMB_2016_Program

TRACK 6 TRACK 6 Technical Program

Further studies will focus on analysis of the specificity of these newly gener- this work we have evaluated a microemulsion technique for incorporation of
ated iron NWs and their internalization into cells. We aim to use this method fluorophore into the silica matrices, optimised it for enhanced encapsulation
as an anti-cancer therapy to specifically target and kill leukemic cells and and free from monomers. Highly fluorescent silica nanoparticles with differ-
allow healthy differentiating blood cells to thrive. ent edges, intended for fluorescent cell imaging, were prepared via simple
modification. Transmission Electron Microscopy, Fourier Transform Infrared
Spectroscopy, Dynamic Light Scattering, and Zeta Potential measurements
Circulating Peptidome to Indicate the Tumor-resident Proteolysis were used to characterize the novel silica nanoparticles by particle size,
functionality, and morphology, as well as by ζ-potential and physical stability.
Poster Presentation. NEMB2016-6084 Interaction of the protein for each of the different nanoparticle terminals was
unique, indicating a strong dependence on surface chemistry[2]. Our studies
indicate that the silica matrix inhibits the aggregation and decomposition
Tony Y. Hu, Houston Methodist Research Insititute, Houston, TX, of cores with outside environment leads to efficient bio-imaging property.
United States, Yaojun Li, Zaian Deng, Houston Methodist Research Furthermore the particle toxicity, indicated by membrane integrity and mito-
Institute, HOUSTON, TX, United States chondrial activity was measured by lactase dehydrogenase (LDH) release,
and tetrazolium reduction (MTT), in both normal and cancer cells. As a result
Tumor-resident proteases (TRPs) are regarded as informative biomarkers for compared to bare dye, multi edged encapsulated dyes showed less toxicity
staging cancer progression and evaluating therapeutic efficacy. Currently in to normal cells which is high toxic to cancer cells.
the clinic, measurement of TRP is dependent on invasive biopsies, limiting
their usefulness as monitoring tools. Here we identified circulating peptides References
naturally produced by TRPs, and evaluated their potential to early diagnose [1] C. Caltagirone, A. Bettoschi, A. Garau, R. Montis, Chemical Society Re-
a cancer or monitor the efficacy of anti-tumor treatments. views, (2015).
In a biomarker study of early tumor diagnosis, we used a breast cancer [2] N.P. Mortensen, G.B. Hurst, W. Wang, C.M. Foster, P.D. Nallathamby, S.T.
mouse model. The nature and extent of peptide cleavage by CPN was Retterer, Nanoscale, 5 (2013) 6372-6380.
investigated by fragment profiling using nanopore fractionation and mass
spectrometry. The fragment profiles in interstitial fluid correlated with con-
centrations of CPN-catalyzed peptides in blood samples taken from the tu- Preparation of a Nano Structure Generation 4.5 Poly (amidoam-
mor-bearing mice, healthy women, and breast cancer patients. CPN expres- ine) Dendrimer and Monoclonal Anti-IL-6 Antibody Conjugate as
sion in the same set of samples was further examined by immunohistochem- Bioimaging Probe and Drug delivery
istry and immunoblotting. We showed that generation of C3f_R1310-L1319
specifically correlated with the CPN expression level. In both the mouse and
clinical patient samples, CPN was clearly increased in tumor tissues com- Poster Presentation. NEMB2016-5917
pared with normal breast tissue, whereas corresponding CPN abundance
in blood remained constant. Concentrations of 6 CPN-catalyzed peptides S.L. Mekuria, H.C. Tsai, National Taiwan University of Science and
predominantly increased in sera taken from the mice (n = 8) at 2 weeks after Techenology, Taipei, 43 Keelung Road, Section 4,Taiwan
orthotopic implantation. Six homologous peptides displayed significantly
higher expression in the patients’ plasma as early as the first pathologic In this study, interleukin-6 (IL-6)-conjugated anionic generation 4.5 (G4.5)
stage of breast cancer. poly (amidoamine) (PAMAM) was synthesized through EDC/NHS coupling
chemistry followed by encapsulation of anticancer drug. Chemical interac-
In another biomarker study of evaluation of anti-tumor efficacy, we estab- tions were confirmed using ζ potential, UV-visible, emission fluorescence
lished a mouse model for ovarian cancer development and treatment by and NMR spectroscopy. After IL-6 conjugation, nanoparticles size increased
orthotopic implantation of the human drug-resistant ovarian cancer cell to approximately 70 nm by forming core-shell nanostructure and zeta poten-
line HeyA8-MDR, followed by porous silicon particle- or multistage vector tial increased from -56.5 ± 0.2 to -19.1 ± 2.4 mV due to neutralization of neg-
(MSV) - enabled EphA2 siRNA therapy. Immunohistochemistry staining of atively charged G4.5. Wide-angle X-ray scattering (WAXS) suggested that
tumor tissue revealed decreased expression of matrix metallopeptidase 9 a layered nanoparticles structure was formed by the G4.5/IL-6 conjugate.
(MMP-9) in mice exhibiting positive responses to MSV-EphA2 siRNA treat- Furthermore, the cellular uptake of the conjugates by HeLa cells was signifi-
ment. We demonstrated, via an ex vivo proteolysis assay, that C3f peptides cantly enhanced in comparison to free G4.5; these results indicated that the
can act as substrates of MMP-9, which cleaves C3f at L1311-L1312 into two described system may be a potential bioimaging probe in vitro. The drug
peptides (SSATTFRL and LWENGNLLR). Importantly, we showed that these encapsulation efficiency of the dendrimer-antibody conjugates was found
two C3f-derived fragments detected in serum were primarily generated by 51.3 %. The cellular uptake and the binding efficiency of drug in the dendrim-
tumor-resident, but not blood-circulating, MMP-9. er-antibody conjugate were also evaluated by confocal microscopy and flow
Our results suggested that the presence of the circulating fragments spe- cytometry in vitro against cervical carcinoma (HeLa) cell lines.
cially derived from the localized cleavage in tumor microenvironment can
be used for early diagnosis of cancer or evaluation of therapeutic efficacy
of anti-cancer treatment, assessed through a relatively noninvasive and us- Chitosan Coated PLGA Nanoparticle as Drug Delivery System
er-friendly proteomics approach.
Poster Presentation. NEMB2016-6129

Multi-edged lightning silica nanoparticles preparation and its ap-
plication on bio-imaging Shalil Khanal, North Carolina A&T State University, greensboro,
NC, United States, Shanta R Bhattarai, Md Anderson Cancer Re-
search Center, Houston, TX, United States, Narayan Bhattarai,
Poster Presentation. NEMB2016-5933
North Carolina A&T State University, Greensboro, NC, United States
Sathya Ramalingam, Raghava Rao Jonnalagadda, Central
Poly (lactide-co-glycolide) (PLGA) based microparticulate formulations have
Leather Research Institute, chennai, tamilnadu, India increasing attention in delivery applications due to theirs capability for sus-
tained and controlled drug release characteristics as well their biocompat-
Amongst inorganic nanoparticles, silica nanoparticles named as “GRAS” ible and biodegradable properties. However due to the shortage of active
(Generally Recognised As Safe) due to its biocompatibility being endoge- functional groups on surface of PLGA, the wide applications of these formu-
nous to most living organisms[1]. Recent activities on development of bio- lations are always limited in targetable drug delivery. In this research, PLGA 73
medical imaging and therapy, more efforts towards the design and synthesis nanoparticles were modified with chitosan (CS), a cationic polysaccharide
of functionalised silica nanoparticles with various prominent properties. In bears repetitive amine groups in backbone through physical adsorption. We