Nanomedicine Commons^™

Multimodal Imaging Of Protein-Based Biomaterials For Delivering Chemo-Agent Cargo For Glioblastoma Treatment In A Murine Model, Orin Mishkit

Dissertations and Theses

Protein-based self-assembling biomaterials, known as Thermo-Responsive Assembled Proteins (TRAP), present meaningful potential as drug delivery carriers. These materials enable the controlled, slow release of poorly soluble chemotherapeutic agents, such as doxorubicin (Dox), while potentially reducing systemic off-target effects. In collaboration with multiple NYU labs, this study evaluated the efficacy of two TRAP variants—TRAP and F-TRAP—as drug delivery carriers in a xenograft mouse model of glioblastoma multiforme (GBM).

The primary objective was to compare the effectiveness of TRAP-loaded Dox (TRAP-DOX) to free Dox in achieving tumor extravasation and accumulation, facilitating sustained drug release. We hypothesized that the leaky vasculature of GBM …

Explorations Of Dna-Single-Walled Carbon Nanotube Interactions To Develop Multiplexed Molecularly Specific Biosensors For Inflammation, Amelia K. Ryan

Dissertations and Theses

Inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-12 (IL-12) are central regulators of immune signaling and key biomarkers of disease, yet existing assays for their detection remain slow, invasive, and lack multiplexing ability. This dissertation advances the development of single-walled carbon nanotube (SWCNT) optical nanosensors capable of real-time, multiplexed, and molecularly specific cytokine detection through innovative use of single-stranded DNA (ssDNA) interfaces.

First, an IL-6-specific DNA aptamer was employed as both a dispersing agent and recognition probe for SWCNT fluorescence sensing. Sequence modifications, including anchor domains, truncations, and thermally induced refolding, were systematically tested to optimize sensitivity and selectivity. The …

Hafnium Oxide-Based Nanoheterostructures For Catalytic Radiosensitization And Enhanced X-Ray Radiotherapy, Marlen Dariela Calix Quezada

Theses and Dissertations

Orthovoltage X-ray beams are attractive for surface and intra-operative radiotherapy. Yet, their clinical utility is constrained by rapid attenuation and the limited dose that can be delivered without harming healthy tissue. High-Z hafnium oxide (HfO₂) nanoparticles can boost local energy deposition through the photoelectric effect, while catalytic surface defects accelerate water radiolysis. Harnessing both mechanisms in a single nano-heterostructure could enable potent radiosensitization at diagnostic-range energies.

This thesis develops and evaluates HfO₂-based nanoheterostructures, both bare and Au-decorated, as catalytic radiosensitizers.

Two types of HfO₂ were evaluated, one was synthesized following a specific route and the …

Targeting Bone In Cancer Therapy: Advances And Challenges Of Bisphosphonate-Based Drug Delivery Systems, Fariba Ganji, Mohammadmahdi Eshaghi, Hossein Shaki, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Background and Purpose: Bisphosphonates (BPs) are well-known for their strong affinity toward bone mineral matrices and are widely used to inhibit excessive osteoclast activity associated with various bone disorders. Beyond their clinical use, their unique bone-targeting capability has positioned them as promising ligands for drug delivery systems aimed at treating bone-related cancers. Approach: The review analyses published studies on BP-functionalized drug delivery systems, including direct drug conjugates, calcium-based nanomaterials, carbon-based nanostructures, and self-assembling systems such as micelles and liposomes. In vitro assays (e.g. hydroxyapatite binding, cell viability) and in vivo biodistribution studies are discussed to evaluate targeting efficiency and …

Cellax Nanoparticles: Taxane Nanoformulations For Solid Tumor Targeting, Lobat Tayebi, Mehran Alavi

Electrical & Computer Engineering Faculty Publications

Nanoparticles (NPs), specifically polymer-modified NPs, have illustrated unique therapeutic advantages compared to bulk materials. Cellax NPs have provided a promising approach to cancer therapy by improving drug delivery, targeting the tumor microenvironment, and potentially overcoming drug resistance, all while reducing overall toxicity compared to traditional taxane treatment. By the flash nanoprecipitation (FNP) method, docetaxel and cabazitaxel have been formulated with polyethylene glycol (PEG) modified-acetylated carboxymethylcellulose (CMC) polymer to increase biocompatibility, bioavailability, specific targeting, and modulate the tumor microenvironment. However, there are some challenges and clinical limitations related to this formulation, encompassing optimum targeted delivery to tumors, overcoming biological barriers, such …

Development Of Novel Carbohydrate-Based Nanoparticles For Precision Drug Delivery, Krystal Ann Hughes

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticle-based drug delivery has made tremendous advancements in the last decade. However, several critical factors, including precision drug delivery at the site of interest, long-term storage stability, and controlling release profiles of drugs in the systemic circulation, need to be addressed for successful clinical translation of nanomedicine. This dissertation presents novel carbohydrate-based nanoparticles that achieve precise intracellular delivery and therapeutic release at the disease site. We present the formulation and optimization of polymeric and polymer-lipid hybrid nanoparticles that enable precision intracellular delivery and passive accumulation of therapeutics in the bone marrow. Intracellular delivery is highly impactful and sought after. One …

Targeting Myeloid Cell Iron Metabolism In Salmonella-Induced Colitis, Mariella Arcos Padilla

Biomedical Engineering ETDs

Salmonellosis is a severe infection caused by Salmonella enterica serovar Typhimurium, leading to significant global morbidity and mortality.

Previous studies have shown that mice lacking the iron storage protein ferritin heavy chain (FTH1) in myeloid cells exhibit worsened Salmonella infection. Nuclear receptor co-activator 4 (NCOA4) directs FTH1 autophagic degradation to release iron from storage during conditions of low iron. However, the role of myeloid NCOA4 in regulating bacterial infections remains unclear.

Here, we found that myeloid NCOA4 deficiency augments spleen iron levels and increases cellular iron accumulation, oxidative stress, and ferroptosis in bone marrow-derived macrophages (BMDM) cells. This deficiency also …

Magnetic Resonance Imaging Trackable Pathology-Triggered Polymersomes Toward Enzyme Replacement Theranostics For Gm1 Gangliosidosis, Dorian Foster

All Dissertations

This dissertation investigates the development and optimization of pathology-responsive polymersomes for simultaneous enhanced magnetic resonance imaging (MRI) and enzyme replacement therapy (ERT) in the treatment of GM1 gangliosidosis (GM1). While therapeutic strategies exist for similar, non-neuropathic lysosomal storage disorders, implementation towards GM1 faces significant challenges due to the blood-brain barrier.

Herein, we developed and characterized a range of low molecular weight hyaluronic acid-b-polylactic acid (HA-PLA) polymersomes (PSs) capable of encapsulating therapeutic enzymes in their hydrophilic core. These polymersomes exhibit pathophysiology-triggered responsiveness, degrading in the presence of acidic conditions, which is characteristic of lysosomes, and enzymes such as hexosaminidase A, which …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Mechanisms Of Extracellular Vesicle Uptake And Implications For The Design Of Cancer Therapeutics, Stephanie R Jackson Cullison, Joseph P Flemming, Kubra Karagoz, Peter J Wermuth, Mỹ G Mahoney

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as …

A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda

Theses & Dissertations

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …

Exosomal Cannabidiol: A Promising Candidate For Targeted Oral Delivery Against Breast Cancer., Disha Nagesh Moholkar

Electronic Theses and Dissertations

Cancer therapies are limited by lack of specificity, selectivity and numerous adverse effects. Repurposing potential anticancer compounds with appropriate drug carriers can help overcome these drawbacks. In our present study, we address the major obstacle for cannabidiol (CBD): its low oral bioavailability, using exosomes. Exosomes (Exo) are promising non-toxic and biocompatible drug delivery vehicles Our project aims are to address the research gap by formulating exosomal cannabidiol (ExoCBD): a tumor-targeted oral delivery system for the treatment of breast cancer. The targeting approach relies on the overexpression of folate receptors at the tumor site by using folic acid functionalized exosomes (FA-Exo). …

Understanding Nanoparticle-Liver Interactions In Nanomedicine, Yuxin He, Yifan Wang, Lin Wang, Wen Jiang, Stefan Wilhelm

Faculty, Staff and Student Publications

Introduction: Understanding the interactions between administered nanoparticles and the liver is crucial for developing safe and effective nanomedicines. As the liver can sequester up to 99% of these particles due to its major phagocytic role, understanding these interactions is vital for clinical translation.

Areas covered: This review highlights recent studies on nanoparticle-liver interactions, including the influence of nanoparticle physicochemical properties on delivery, strategies to enhance delivery efficiency by modulating liver Kupffer cells, and their potential for treating certain hepatic diseases. Additionally, we discuss how aging impacts the liver's phagocytic functions.

Expert opinion: While liver accumulation can hinder nanomedicine safety and …

Generation And Characterization Of Lipid Nanoparticles For Dna Plasmid Delivery And Pharmacological Characterization, Sahana John

Biotechnology Theses

Lipid nanoparticles (LNPs) have shown promise for delivering nucleic acids like DNA plasmids, but packaging large plasmids remains challenging. The findings and experimental work detailed in this thesis are geared towards providing a proof of concept and providing preliminary confirmation of the guiding principle.

We synthesized LNPs containing cationic lipids (D-Lin-MC3) to encapsulate the large pLVX-ZsGreen and psiCHECK (luciferase) plasmids (~10-14kb) using a microfluidic system. Characterization included size, charge, morphology, plasmid encapsulation efficiency and in vitro/in vivo studies. The LNP-pDNA particles were ~100nm in size with high encapsulation efficiency. The LNPs efficiently transfected 293T cells with low cytotoxicity, enabling strong …

Translational Pathways For Ultra Long-Acting Medicines For Chronic Disease: From Hiv To Substance Use Disorders, Suyash Sanjay Deodhar

Theses & Dissertations

Human immunodeficiency virus (HIV) and opioid use disorder (OUD) are among the top global public health challenges, with a significant overlap in the number of cases and higher mortality risks compared to the general population. Treatment and recreational opioid use lead to addictive disorders. Both conditions require repeated dosing of therapy where adherence to a strict lifelong regimen remains a major challenge. Notably, people living with HIV/AIDS (PLWHA) and struggling with opioid use disorders (OUD) show suboptimal adherence to antiretroviral drugs (ARVs). Also, the risk of transmitting HIV and other blood-borne infections through the sharing of needles and other injection …

Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das

Theses & Dissertations

Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …

Chitosan-Based Hydrogels In Drug Delivery, Salma A. Fereig, Mona Mohamed Ahmed Abdelmottaleb

Pharmacy

Hydrogels are three-dimensional cross-linked hydrophilic polymers that are able to absorb large quantities of water and swell. They have various properties like biocompatibility, low toxicity, and mostly biodegradability, which make them attractive for drug delivery applications. Chitosan hydrogels are especially attractive due to the inherent activities of the chitosan itself like the antibacterial, anti-inflammatory, and tissue regeneration enhancement capacity. Therefore, chitosan hydrogels have been proposed for the delivery of various drugs, genes, cytokines, and stem cells via various routes of administration for the treatment of various diseases as well as different forms of degeneration.

Development Of Liposomes Using Microfluids For Delivery Of Mir-205, Victoria Herrera, Rahul Tiwari, Meghana Kolli, Neeraj Chauhan, Amber M. Garza, Eswara Naga Hanuma Kumar Ghali, Subhash C. Chauhan, Murali Yallapu

Research Symposium

Background: The therapeutic application of microRNA(s) in the field of cancer has generated significant attention in research. miR-205 is a tumor suppressor in various cancers. However, the delivery of miR-205 is an unmet clinical need. Thus, the development of liposomal formulation platform to deliver miR-205 is highly sought. The most common applications of liposome formulations are vaccines and anticancer formulations (e.g., mRNA, small molecule drugs). However, large-scale production with precise control of size and size distribution of the lipid-based drug delivery systems (DDSs) is one of the major challenges in the pharmaceutical industry. The objective of this study is to …

Characterization Of Biological Particles Using An Integrated Hyperspectral Imaging And Machine Learning, Kaeul Lim, Arezoo Ardekani

Graduate Industrial Research Symposium

Hyperspectral imaging (HSI) is a promising modality in medicine with many potential applications. This study focuses on developing a label-free lipid nanoparticle characterization method using a convolutional neural network (CNN) analysis of HSI images. The HSI data, hypercube, consists of a series of images acquired at different wavelengths for the same field of view, providing continuous spectra information for each pixel. Three distinct liposome samples were collected for analysis. Advanced image preprocessing and classification methods for HSI data were developed to differentiate liposomes based on their material compositions. Our machine learning-based classification method was able to distinguish different liposome types …

Using Imaging Modalities To Predict Nanoparticle Distribution And Treatment Efficacy In Solid Tumors: The Growing Role Of Ultrasound, Michaela B. Cooley, Dana Wegierak, Agata A. Exner

Faculty Scholarship

Nanomedicine in oncology has not had the success in clinical impact that was anticipated in the early stages of the field's development. Ideally, nanomedicines selectively accumulate in tumor tissue and reduce systemic side effects compared to traditional chemotherapeutics. However, this has been more successful in preclinical animal models than in humans. The causes of this failure to translate may be related to the intra- and inter-patient heterogeneity of the tumor microenvironment. Predicting whether a patient will respond positively to treatment prior to its initiation, through evaluation of characteristics like nanoparticle extravasation and retention potential in the tumor, may be a …