TechConnect 2018 an SBIR/STTR Haven

TechConnect #techconnect keeps getting better every year! Anaheim was a great location, with a good mix of entrepreneurs and investors! Looking forward to the next one in Boston in May 2019. I chaired a very engaging panel of experts who elaborated on the biggest problem facing the industrial production of uniform nanoparticles. I showcased Notre Dame’s expanding Nanoparticles synthesis capabilities. Prof. Leevy talked about the challenges of being an entrepreneur in an academic setting and how Notre Dame’s IDEA center #IDEAcenter is making that process easier. Dr. Andrew Wang, the co-founder of Ocean Nanotech and Alpha  BioBeads, talked about the current challenges of commercially synthesizing nanomaterials. Dr. Wei Wang or Saudi Aramco Research Center further expounded on the need to translate nanotechnology from a working concept in the lab to a fully working field instrument in challenging environments such as offshore oil wells. Finally, Dr. Parlak who founded ‘Qatch diagnostics technologies’ talked about the joys, pains and unique satisfaction of running a startup.

College of Science Joint Annual Meeting (CoS-JAM) Poster Presentation (May 4, 2018)

The poster presented by the undergraduate researchers (Margo Waters and Veronica Kalwatjys), explaining their work on a rationally designed, modular antimicrobial nanoparticle system was well received at COS-JAM 2018. Margo worked on the synthesis of the antimicrobial nanoparticles. Veronica has started testing the antimicrobial properties of these nanoparticles under the direction of Dr. Juliane Hopf. The antimicrobial peptides were sourced from Francisco Fields of Prof. Shaun Lee’s lab.

In a time where we are facing an antibiotic resistance crisis, it is necessary to develop non-conventional antimicrobial substances. One possible route is the development of antimicrobial peptides on nanoparticles. The overall goal of our project is to determine if antibacterial peptides linked to antibacterial nanoparticles can completely inhibit bacterial growth. If we are successful, these particles have the potential to be coated onto orthopedic implants and surgical instruments, among others. The combination of antimicrobial peptides with nanoparticles will help to prevent infections following a surgery, thereby preventing the over-use of antibiotics. This could potentially decrease the development of new strains of antibiotic-resistant bacteria.


Society for Biomaterials (SFB) 2018 SYMPOSIUM

SFB 2018 from April 11 to April 14 was a great opportunity to meet experts in the field of immuno-engineering, biomedical imaging, and biomedical devices. The highlight of the trip was the information session held NIBIB on their latest program focussed on engineering immune responses.

Title: In Vivo Detection of Cancer Stem Cells by Dual Mode CT/Fluorescence Using Immunotargeted Nanoparticle Probes
Authors:  P. Nallathamby*1, K. Dahl2, R. Roeder1;
1University of Notre Dame, Notre Dame, IN,
2Indiana University School of Medicine – South Bend, South Bend, IN
3Center for Nanoscience and Technology [NDnano]
Abstract Control ID: # 267

Title: Cytocompatibility of Hafnium Oxide Nanoparticle Imaging Probes Prepared Using a Novel Templated Synthesis
Authors:  P. Nallathamby*1, V. Sokolova3, O. Prymak3, M. Epple3, R. Roeder1;
1University of Notre Dame, Notre Dame, IN,
2Center for Nanoscience and Technology [NDnano]
3Inorganic Chemistry–University of Duisburg-Essen, Essen, Germany
Abstract Control ID: # 984


MRS 2018 Spring Symposium,

I will be at MRS 2018 from April 1 to April 5 presenting my work on novel cancer therapeutics

Title: Biocompatible, Radiotherapeutic Hafnium Oxide Nanoparticle Imaging Probes Prepared Using a Novel Templated Synthesis
Abstract Control ID: # 2884959
Paper # NM05.01.05
Presentation Date: April 2, 2018
Presentation Time: 9:30 AM to 9:45 AM
Location: PCC North, 200 Level, Room 229 B

Title: Magnetoelectric Nanoparticles for Targeted Drug Delivery of Novel Chemotherapeutic Cocktails to Prevent Metastasis of Breast Cancer Cells
Abstract Control ID: # 2885296
Paper # NM07.06.04
Presenting Author: Prakash Nallathamby
Presentation Date: April 5, 2018
Presentation Time: 4:00 PM to 4:15 PM
Location: PCC North, 200 Level, Room 231 A

6th Annual Advanced Diagnostics and Therapeutics (AD&T) Symposium – March 6, 2018

Undergraduate Research Assistant Margo Waters (Sophomore), at her first poster presentation. Margo synthesizes the anisotropic nanoparticles being used in the ongoing study looking into the applications of antimicrobial peptides@nanoparticles as surfactants on implant materials and medical devices. The project lead is Dr. Juliane Hopf and her undergraduate mentee is Veronica Kalwatjys. The work is in collaboration with Prof. Shrout’s lab and Francisco Fields of Prof. Lee’s lab.



“Super-resolution fluorescence microscopy by stepwise optical saturation” by Yide Zhang et al. I am happy to have supplied Yide Zhang with the fluorescent nanoparticle probes that he used in this proof of concept paper for a new super-resolution technique that he co-invented with his adviser.

Cytocompatibility of Hafnium Oxide Nanoparticle Imaging Probes Prepared Using a Novel Templated Synthesis

Figure 1. (A) TEM micrograph of an individual HfOR2R NP. Scale bar = 5 nm. (B) X-ray radiograph and (C) fluorescence of CY5-HfOR2R NPs in an Eppendorf tube. (D) Hydrodynamic diameter of HfOR2R NPs and CY5-HfOR2R NPs in water over 24 h. (E,F) Live/Dead assay confirmed >99% viability and (G,H) confocal microscopy confirmed cellular uptake of CY5-HfOR2R NPs in (E,G) HeLa and (F,H) THP-1 cells. Scale bars = 20 m

This work will be presented at MRS 2018 and at SFB 2018

Statement of Purpose: Hafnium oxide (HfO2) with a k-edge of 50 keV is being explored as a clinical X-ray contrast agent. HfO2 NPs are also in clinical trials as radiosensitizers that induce immune action against tumor sites.   However, the unpredictable stability of commercially available HfO2 makes it hard to predict their pharmacokinetics and their size range of ((50-100 nm) results in zero clearance from an in vivo system. Therefore, in this study we have executed a modular approach for the design and scalable synthesis of novel, non-sintered, 4-8 nm metal oxide nanoparticles (e.g. Hafnium oxide, Gadolinium oxide) with 40-60 fold higher X-ray attenuation cross-sections than the NPs diameter. Contrast-enhanced computed tomography (CT) and spectral (color) X-ray CT with the aid of these new class of probes have the potential to enable targeted image guided therapeutics with CT as a lower cost and higher resolution alternative to PET and MRI.

Results: We achieved >95% efficient conversion of the amorphous seed NPs to crystalline orthorhombic-HfO2 NPs. HfO2 NPswere ~4-5 nm in diameter (Fig. 1A) and formed non-sintered flocculants, 220-290 nm in diameter. As-prepared CY5-HfO2 NPs exhibited simultaneous X-ray contrast and fluorescence in multispectral imaging (Fig. B,C). Both HfO2 and CY5-HfO2 NPs remained well-dispersed over 24 h (Fig. 1D). The measured zeta potential was -13 to -16 mV. Encapsulating the HfO2 NPs in a SiO2 shell reduced the hydrodynamic diameter to ~30 nm and inhibited the formation of flocculants. MTT and Live/Dead assays confirmed that the HfO2 NPs were neither cytotoxic nor pro-inflammatory (Fig. 1E,F). Confocal microscopy confirmed highly efficient uptake of Cy5-HfO2 NPs by HeLa cells and THP-1 cells (Fig. 1G,H).

Conclusion: HfO2 NPs were prepared using a novel templated synthesis resulting in crystalline NPs, ~4-5 nm in diameter, which flocculate into 220-290 nm clusters. Therefore, these NPs are anticipated to provide both long blood circulation and eventual renal clearance through phagocytic breakdown after delivery as radiographic imaging probe or radiosensitizer.

Acknowledgments: NSF DMR-1309587, DAAD PPP, Notre Dame GCI, Walther Cancer Foundation, NDnano.

Contributors:  Prakash D. Nallathamby,1 Viktoriya Sokolova,2 Oleg Prymak,2 Matthias Epple2 and Ryan K. Roeder 1

1University of Notre Dame

2University of Duisburg-Essen