Research Highlight


A. The Digital Diffraction Diagnostic (D3) device. This device is a miniature, portable, lens free imaging device developed at MGH for cancer diagnosis in low- and middle- income countries. B. Holographic image taken by D3 of polystyrene beads and silica beads. These beads are conjugated with DNA probes. In the presence of high risk HPV DNA, two bead-probe conjugates will form a dimer. C. A reconstruction of the holographic image: brighter spots represent a polystyrene bead, darker spots represent a silica bead, and the red arrows point to polystyrene-silica bead dimers representing the presence of HPV DNA. This reconstruction can be done remotely by uploading the holographic image to a secure cloud.

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

More than 85% of women who die of cervical cancer live in low- and middle- income countries1. The main reason for this disparity is that methods of combating cervical cancer exist, but are often not accessible in resource limited areas. Over 90% of cervical cancer develops from a persistent infection with a high risk type of human papilloma virus (HPV)2, meaning early detection and treatment of high risk Human papilloma virus types can prevent cervical cancer fatalities. However, detection is expensive, time consuming, and requires specialized equipment. Therefore to prevent cervical cancer deaths, an inexpensive and easy-to-use assay must be developed that can detect high risk HPV at the point of care. This project is to develop a high-throughput screening assay for four of the most common high risk HPV types directly from patient samples using an integrated portable device based on lens-free imaging. The device can be created using a 10x10mm glass coverslip coated with PDMS which is etched to create multiple lanes. Surface functionalization chemistry will be used to attach DNA probes for four HPV types, one in each lane. DNA from patients’ cervical brushings will be captured by complementary DNA probes. Magnetic microbeads conjugated to DNA probes will be attracted towards the functionalized surface by use of a magnet, and then magnetically washed away. Target DNA will capture the magnetic beads with the corresponding probe, and these beads will remain specifically bound to HPV-specific DNA while other beads are washed away. Using the Digital Diffraction Diagnostic (D3) lens free imaging device previously developed and optimized at MGH3, the beads in each lane will be counted to accurately diagnose the patient. This device will be further optimized to diagnose multiple patients simultaneously. A new innovation from the precedent system is implementing an isothermal amplification known as Recombinase Polymerase Amplification (RPA). The isothermal DNA amplification will replace the conventional PCR requiring a thermocycler and be well suited for use in resource limited settings. Cervical cancer mortality can be prevented by the detection and treatment of high risk HPV, and the vision of this project is to make that possible across the world. 1. World Health Organization. (June 2016). Human Papillomavirus (HPV) and cervical cancer [Fact sheet]. Retrieved from http://www.who.int/mediacentre/factsheets/fs380/en/. 2. American Cancer Society. (5 December 2016). What are the risk factors for cervical cancer [Fact sheet]. Retrieved from https://www.cancer.org/cancer/cervical-cancer/causes-risks-prevention/risk-factors.html. 3. Hyungsoon Im, Cesar M. Castro, Huilin Shao, Monty Liong, Jun Song, Divya Pathania, Lioubov Fexon, Changwook Min, Maria Avila-Wallace, Omar Zurkiya, Junsung Rho, Brady Magaoay, Rosemary H. Tambouret, Misha Pivovarov, Ralph Weissleder, and Hakho Lee. Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone. PNAS 2015 112 (18) 5613-5618; published ahead of print April 13, 2015, doi:10.1073/pnas.1501815112

 

 

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:

In vivo investigation of the pathogenesis and development of pituitary adenomas in relation to the loss of MEG3 expression

Surface-targeting, ligand-switching nanoparticles for mitochondrial drug delivery in prostate cancer

Nanoencapsulation of tyrosine kinase inhibitors and their effects on pathway inhibition

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

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

Discovering the Genetic Mechanism of Enhanced Metastatic Colonization in SMAD4 Mutant Tumors

Radiotherapeutic synergism of thermogelling cisplatin-loaded polymers for cervical cancer treatment

Identifying genomic and compound dependencies in undifferentiated sarcomas

Nano-Talazoparib and Nano-Dinaciclib Combination Therapy for Lung Cancer Cells

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

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

Creating Animal Models of High-grade Serous Ovarian Cancer Cells

Molecular Analysis of Plasma Vesicles for Early Pancreatic Cancer Detection

Role of ESRP1/ESRP2 splicing regulators in the development of Triple-Negative Breast Cancer

Metabolite Quantification from Cancer Tissues using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging

Software with built-in neuroanatomy atlas provides insight into cancer treatment

Quantification of SPION accumulation in tumors using positive-contrast MRI

Using smart biomaterials with immunoadjuvants to treat metastatic breast cancer

Enhanced delivery of camptothecin and doxorubicin conjugates with hyaluronic acid for the treatment of Glioblastoma using microbubble-mediated focused ultrasound

MCT1 Transporter Inhibition of IMR90 Cells Expressing Inducible Merkel Cell Carcinoma Small T Antigen

Characterization of Nano-Dinaciclib in Combination with Nano-Talazoparib for the Treatment of Breast Cancer

Radiation enhancement in cancer cells using gold and gadolinium nanoparticles

Development of a novel nanogel for non-invasive transdermal delivery of cancer vaccines using hyaluronic acid

Combined Cisplatin and Olaparib nanoparticles for ovarian cancer therapy

Targeted Delivery of Talazoparib to Treat Non-Small Cell Lung Cancer

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