Research Highlight


A) NIRF images showing the accumulation of the MN-EPPT probe in colon tumors. The tumor on the left lacks the uMUC-1 antigen (uMUC-1 -), while the tumor on the right does have the uMUC-1 antigen (uMUC-1 +). Signal from the probe is much higher in the uMUC-1 + tumor, as demonstrated by the center and right images showing raw fluorescence and a color coded map, respectively. B) NIRF images of excised tumor C) Fluorescence microscopy of the probe in excised tissue. Images demonstrate that the nanoprobe retained its structural integrity.

Tracking pancreatic adenocarcinoma response to treatment using targeted, multi-modal nanoparticles

Early diagnosis and efficient treatment of tumors are essential to the survival of cancer patients. New molecular based therapies are beginning to allow treatment regimens that take advantage of a tumor's unique molecular characteristics. However, there is a need for more sophisticated imaging techniques to enable the effective application of these therapies. Imaging probes that are able to target tumors would help to facilitate earlier diagnoses, monitor tumor response to existing therapies, and facilitate the development of novel therapeutics. One class of probe currently being studied and refined are cross-linked, iron oxide nanoparticles carrying EPPT peptides. This molecule is a targeted, multi-modal imaging probe referred to as MN-EPPT. The EPPT peptide attached to the nanoparticle’s dextran coat is able to bind to the underglycosylated mucin-1 antigen, (uMUC-1) which is specifically expressed on the surface of human adenocarcinomas. As a result, the probe is able to accumulate selectively in tumor cells. uMUC-1 is present on almost 50% of all human cancers, including breast, prostate, lung, and pancreatic cancers, among others. The nanoparticles are designed for use with two different, yet complementary imaging modalities. The iron oxide is superparamagnetic, which means it is viable as a contrast agent for MR imaging. Furthermore, MN-EPPT particles are coated with a Cy5.5 dye, which allows them to be used for optical near-infrared imaging (NIRF). This dual functionality lets the probe take advantage of the unique benefits of each type of imaging. MRI provides high spatial and temporal resolution, and NIRF is known for its sensitivity. In addition, the presence of Cy5.5 dye allows for correlative fluorescence microscopy of excised tissues. The current project will evaluate MN-EPPT’s utility as a device for assessing tumor response to a standard chemotherapeutic, Gemcitabine, in a preclinical model of orthotopic pancreatic adenocarcinoma. This study will also validate the work done in previous projects that demonstrated MN-EPPT’s ability to accumulate selectively at the site of the tumor. Both MR and NIRF imaging will be used to examine the probe's feasibility as a tool for tracking changes in tumor size. In addition, we will investigate whether Gemcitabine causes downregulation of uMUC1 antigen during treatment, which may affect MN-EPPT’s ability to accumulate in tumor cells. This will be done by investigating uMUC1 mRNA expression and correlating it with MN-EPPT accumulation in tumors.

 

 


Trainee Research

CaNCURE provides trainees with a 6-month hands-on research experience and one-on-one mentoring by leading researchers in cancer nanomedicine.   Projects performed by current and past participants include:

Targeted Delivery of Liposomes using PARP Inhibitors to Treat Non-Small Cell Lung Cancer

Localized chemo- and chemo-radiation for the treatment of prostate cancer

Tracking pancreatic adenocarcinoma response to treatment using targeted, multi-modal nanoparticles

Implementation of novel MR-based attenuation correction in PET/MR pelvic scans

Uptake and localization of nanoparticles in prostate and lung cancer cells as a function of time and nanoparticle type

Delivery of Titanium Dioxide Nanoparticles via Biodegradable PLGA Dissolving Microneedles for Sustainable Release

Investigating the use of iron chelator deferoxamine (DFO)-bearing PEG-like nanoprobes as a multifunctional agent for cancer therapy and PET imaging

In vivo imaging of targeted drug delivery to HER2 positive cancer cells

Co-delivery of protective substrate and chemotherapy drugs via lipid Bilayer Mesoporous Silica Nanoparticles

Biological mechanisms of gold nanoparticle-enhanced radiation therapy of prostate cancer

Radiation enhancement in cancer cells using gold and gadolinium nanoparticles

Quantitative Multimodal Imaging of Tumor Response to Radiation

Identifying genomic and compound dependencies in undifferentiated sarcomas

PDT and PIT with Chemotherapy for Treatment of 3D Ovarian Cancer Nodules Under Flow and Static Conditions

Molecular Analysis of Plasma Vesicles for Early Pancreatic Cancer Detection

Erythropoietin improves antitumor immune response through reversal of the hypoxic tumor microenvironment

Nanoencapsulation of tyrosine kinase inhibitors and their effects on pathway inhibition

Investigation of a miRNA associated with cancer metastasis. Proj 2-Development of a novel nanoparticle for MPI analysis of thromboses

Targeting WASp using Wiskostatin-gold nanoparticles

Iron-chelating PEG-like nanoprobes as therapeutic and 89Zr/PET imaging agents

Nano-plasmonic exosome (nPLEX) assays for exosome analysis and antibody validation

Development of a Point of Care Assay for Detecting High Risk HPV in Resource Limited Settings

Development of Smart INCeRT Brachytherapy Spacers via PLGA and Docetaxel for Combined Chemo-Radiation Therapies in Prostate Cancer

Combined delivery of targeted liposomal chemotherapeutics and photodynamic therapy to treat pancreatic cancer

Assessment of Atherosclerotic Changes using Ferumoxytol as MRI Contrast Agent


Soleil Doggett (Biology, '16) talks to her fellow peers about her research on oxygenating tumors to stimulate the anti-tumor immune response.

 


Trainee e-portfolios

Photo credit: Tom Kates Photography

While on co-op, trainees document their research in an e-portfolio.  This gives trainees the opportunity to provide regular updates on their research progress, reflect on training they are receiving, and explain how their research fits within the field of cancer nanomedicine.  These research e-portfolios can be accessed through individual trainee profiles.  The complete collection may be found here.

 


Presentation at CaNCURE Nanomedicine Day

At the completion of their co-op, trainees are provided with the opportunity to present their research to a wider audience.  For our June CaNCURE Nanomedicine Day, trainees prepare interactive, digital posters to display on electronic poster boards.  Over 100 faculty, students, and researchers attend this annual event!

Check out the news article about our first CaNCURE Day!


Trainee Publications

Our Trainees have published 22 peer-reviewed since January 2015.  A full list of Trainee publications is found below.

  1. Patrick Sheedy, Zdravka Medarova. The fundamental role of miR-10b in metastatic cancer. Am J Cancer Res 2018;8(9):1674-1688. Link
  2. Chen X, Ling X, Zhao L, Xiong F, Hollett G, Kang Y, Barrett A, Wu J. “Biomimetic Shells Endow Sub-50 nm Nanoparticles with Ultrahigh Paclitaxel Payloads for Specific and Robust Chemotherapy.”  ACS Appl Mater Interfaces. 2018 Sep 25. doi: 10.1021/acsami.8b11571. PMID: 30203956  Link
  3. Hedgire S, Krebill C, Wojtkiewicz GR, Oliveira I, Ghoshhajra BB, Hoffmann U, Harisinghani MG. “Ultrasmall superparamagnetic iron oxide nanoparticle uptake as noninvasive marker of aortic wall inflammation on MRI: proof of concept study.”   Br J Radiol. 2018 Sep 12:20180461. doi: 10.1259/bjr.20180461. PMID: 30160173  Link
  4. Application of the BLADE Sequence in Upper Abdominal MR Imaging. Krebill C.  Radiol Technol. 2018 May;89(5):495-497. PMID:29793909 Link
  5. Torrado-Carvajal A, Vera-Olmos J, Izquierdo-Garcia D1, Catalano OA, Morales MA, Margolin J, Soricelli A, Salvatore M, Malpica N, Catana C1. Dixon-VIBE Deep Learning (DIVIDE) Pseudo-CT Synthesis for Pelvis PET/MR Attenuation Correction. J Nucl Med. 2018 Aug 30. pii: jnumed.118.209288. doi: 10.2967/jnumed.118.209288. PMID: 30166357  Link
  6. Xiaoyuan Ji, Jie Wang, Lin Mei, Wei Tao, Austin Barrett, Zhiguo Su, Shaomin Wang. Guanghui Ma, Jinjun Shi, Songping Zhang. Artificial Photosynthesis: Porphyrin/SiO2 /Cp*Rh(bpy)Cl Hybrid Nanoparticles Mimicking Chloroplast with Enhanced Electronic Energy Transfer for Biocatalyzed Artificial Photosynthesis. Advanced Functional Materials. Link
  7. Yang KS, Im H, Hong S, Pergolini I, Del Castillo AF, Wang R, Clardy S, Huang CH, Craig Pille, Ferrone, Yang R, Castro CM, Lee H, Del Castillo CF, Weissleder R. Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy. Sci Transl Med. 2017; 9(391): eaal3226. PMC5846089
  8. Zhu X, Ji X, Kong N, Chen Y, Mahmoudi M, Xu X, Ding L, Tao W, Cai T, Li Y, Gan T, Austin Barrett, Bharwani Z, Chen H, Farokhzad OC. Intracellular Mechanistic Understanding of 2D MoS2 Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy.  ACS Nano. 2018 Mar 27;12(3):2922-2938. PMC6097229
  9. Miller MA1, Kim E, Cuccarese MF, Alec Plotkin, Prytyskach M, Kohler RH, Pittet MJ, Weissleder R. “Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor associated macrophage uptake in metastatic disease.” Chem Commun. 2017 Dec 19;54(1):42-45. PMC5736449
  10. Ding L, Zhu X, Wang Y, Shi B, Ling X, Chen H, Nan W, Austin Barrett, Guo Z, Tao W, Wu J, Shi X. “Intracellular Fate of Nanoparticles with Polydopamine Surface Engineering and a Novel Strategy for Exocytosis-Inhibiting, Lysosome Impairment-Based Cancer Therapy”. Nano Lett. 2017 Nov 8;17(11):6790-6801.  PMC6071871
  11. Yoo B, Ann-Marie, Billig, Medarova Z. “Guidelines for Rational Cancer Therapeutics. Frontiers in Oncology Journal”. Front Oncol. 2017 Dec 12;7:310. PMC5732930
  12. Gharagouzloo C, Timms L, Qiao J, Fang Z, Joseph Nneji, Pandya A, Kulkarni P, van de Ven AL, Ferris C, Sridhar S. “Neural circuits and brain function: New insights using quantitative vascular mapping of the rat.” Neuroimage, 2017. 16C:24-33  PMC5824692
  13. Gharagouzloo C, Timms L, Qiao J, Fang Z, Joseph Nneji, Pandya A, Kulkarni P, van de Ven AL, Ferris C, Sridhar S.   “Dataset on a 173 region awake resting state quantitative cerebral blood volume rat brain atlas and regional changes to cerebral blood volume under isoflurane anesthetization and CO2 challenge”. Data in Brief, 2018. 17:393-396.  Link
  14. Qin L, Li A, Qu J, Reinshagen K, Li X, Cheng S, Annie Bryant, Young GS. Normalization of ADC does not improve correlation with overall survival in patients with high-grade glioma (HGG). J Neurooncol. 2018 Apr;137(2):313-319.   PMC6071871
  15. Belz J, Kumar R, Baldwin P, Noelle Castilla Ojo, Leal AS, Royce DB, Di Zhang D, van de Ven AL, Liby K, Sridhar S. “Sustained-release Talazoparib implants for localized treatment of BRCA1-deficient breast cancer”. Theranostics, 7(17): 4340-4349.  PMC5695017
  16. Qin L, Li X, Amanda Stroiney, Qu J, Helgager J, Reardon DA, Young GS. “Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma.” 2017 Feb;59(2):135-145.  PMC6097616
  17. Jodi Belz, Noelle Castilla Ojo,Srinivas Sridhar, Rajiv Kumar.  Radiosensitizing silica nanoparticles encapsulating docetaxel for treatment of prostate cancer, In Cancer Nanotechnology. Reema Zeineldin (Ed).  Series: Methods in Molecular Biology. Springer Press. Methods Mol Biol. 2017; 1530:403-409. PMC5531609
  18. Christian Berrios, Megha Padi, Mark A. Keibler, Donglim Esther Park, Vadim Molla, Gregory Stephanopoulos, John Quackenbush, James A. DeCaprio. “Merkel cell polyomavirus small T antigen promotes pro-glycolytic metabolic perturbations required for transformation”. 2016 Nov 23;12(11):e1006020.   PMC5120958
  19. Song C, Liu Y, Rachel Fontana, Makrigiorgos A, Mamon H, Kulke MH, G. Mike Makrigiorgos. “Elimination of unaltered DNA in mixed clinical samples via nuclease-assisted minor-allele enrichment”.  2016 Nov 2;44(19):e146. PMC5100565
  20. Andrew L. Hong, Yuen-Yi Tseng, Glenn S. Cowley, Oliver Jonas, Jaime H. Cheah, Bryan D. Kynnap, Mihir B. Doshi, Coyin Oh, Stephanie C. Meyer, Alanna J. Church, Shubhroz Gill, Craig M. Bielski, Paula Keskula, Alma Imamovic, Sara Howell, Gregory V. Kryukov, Paul A. Clemons, Aviad Tsherniak, Francisca Vazquez, Brian D. Crompton, Alykhan F. Shamji, Carlos Rodriguez-Galindo, Katherine A. Janeway, Charles W. M. Roberts, Kimberly Stegmaier, Paul van Hummelen,
Michael J. Cima, Robert S. Langer, Levi A. Garraway, Stuart L. Schreiber, David E. Root,
William C. Hahn, & Jesse S. Boehm. “Integrated genetic and pharmacologic interrogation of rare cancers”. Nat Commun. 2016 Jun 22;7:11987.  PMC4917959
  21. Wang P, Yoo B, Sherman S, Mukherjee P, Ross A, Pantazopoulos P, Petkova V, Farrar C, Medarova Z, Moore A. “Predictive imaging of chemotherapeutic response in a transgenic mouse model of pancreatic cancer.” Int J Cancer. 2016 Aug 1;139(3):712-8. PMCID: PMC4925171
  22. Nazila Kamaly, Gabrielle Fredman, Jhalique J. Fojas, Manikandan Subramanian, Won II Choi, Katherine Zepeda, Cristian Vilos, Mikyung Yu, Suresh Gadde, Jun Wu, Jaclyn Milton, Renata Leitao, Livia Rosa, Moaraj Hasan, Huayi Gao, Vance Nguyen, Jordan Harris, Ira Tabas, and Omid C. Farokhzad. “Interleukin-10 Targeted Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis”. ACS Nano. 2016 May 24;10(5):5280-92. PMC5199136