Engineering nanomaterials for cancer theranostics

This thesis aims to engineer novel nanomaterial to target receptors on the surface of cancer to diagnose and deliver cytotoxic drugs or siRNA selectively. Receptor-targeting peptides have been relatively unexplored to deliver nanomaterial to cancer. The paucity is due to the challenge associated with the synthesis in assembling the components on a nanomaterial. We developed a universal methodology to overcome the synthetic difficulty and generated a library of peptide-targeted nanomaterial. These materials are targeted towards the following receptors: PD-L1, GRPR, and cMET, which are overexpressed in cancers. In addition, we investigated the diagnostics efficacy of nanomaterials targeted towards PD-L1, and the results showed the unique advantage of these classes of particles to quantify the receptors. Finally, we evaluated the in vitro and in vivo (in GRPR) efficacy of the targeted nanomaterials attached with the Doxorubicin drug in ovarian and hepatocellular cancers. The in vitro results established the superiority of the targeted material over the conventional chemotherapeutics. However, the in vivo evaluation of GRPR targeted nanomaterials showed only moderate efficacy compared with the chemo drug. Importantly, all the animals administered with targeted nanomaterial were healthy and alive at the end of the study; in contrast, all mice administered with doxorubicin succumbed to death. During this study, we gathered that targeted delivery of chemotherapeutics alone might be insufficient to overcome drug resistance and genetic inhibition is imperative. Therefore, we developed another nanomaterial to deliver two siRNAs to co-inhibit drug-resistant proteins and performed preliminary cancer cells. Further studies are warranted to establish this as a therapeutic modality. The experience allowed us to embark on an audacious project wherein we used non-cancer drugs to treat the tumor. Based on the solid scientific rationale, we combined COPD drug and tyrosine kinase inhibitor to treat lung cancer, and the results show benefit. The significance of this study is that the engineered nanomaterial possesses the potential to deliver the drug to cancer, reduce toxicity, and overcome drug resistance; further studies using clinically relevant patient-derived xenograft mouse models help translate the materials to clinics for patient benefits.Includes bibliographical references

Near infrared navigation system (NAVI) for real time visualization of blood flow

Poster presented at the 2017 Health Sciences Research Day which was organized and sponsored by the University of Missouri School of Medicine Research Council and held on November 9, 2017.Summary: A portable and economical NAVI camera system that can be utilized for intraoperative fluorescence imaging has been fabricated. The NAVI system has been validated by conducting preclinical grafting studies in swine model. Finally, the clinical translational capability of the NAVI imaging system has been established using suitable clinical studies. Future study: The NAVI imaging system is being explored for lymph node imaging and other applications

MoS₂/WS₂/BN-Silver Thin-Film Hybrid Architectures Displaying Enhanced Fluorescence via Surface Plasmon Coupled Emission for Sensing Applications

Extremely thin layers of MoS₂, WS₂, and BN have come to the fore as a “beyond graphene” class of emerging 2D-materials that display many interesting properties and have wide technological applications. In this study, we report the first time engineering of these novel nano 2D-materials as efficient spacer layer components in silver (Ag) based thin-film stacks that generated up to 17-fold enhancement in the emission intensity of rhodamine B (RhB) fluorophore molecules; based on the surface plasmon coupled emission (SPCE) platform. The exceptional mechanical, thermal, and chemical stability of these 2D-spacer layers enabled effective surface passivation of Ag thin-films. The superior signal enhancements observed from the different 2D-spacer substrates may be attributed to optimal changes in radiative decay rates of excited RhB states. In a manner not reported before, we demonstrate the tunability of SPCE signal enhancements, on choosing spacer materials of appropriate refractive index. In this work, we further present a detailed comparison between MoS₂/WS₂/BN, and also nanocarbon allotropes like graphene and C₆₀, which we have previously reported as high-performance spacers in biosensing applications. The low-cost fabrication of Ag-(MoS₂/WS₂/BN) thin-film architectures, synergistically coupled with superior fluorescence signals produced by SPCE, promises the application of these portable platforms for the detection of various biochemical analytes with very high levels of sensitivity