2024 Cancer Innovation Scholars
Project Title: Protein Corona Formation and Aggregation Studies on Targeted Drug Delivery Nanoparticles for Triple-Negative Breast Cancer
REU Scholar: Ange Mendez (North Carolina State University), Advisor: Kathleen McEnnis
Abstract: Protein corona formation and aggregation studies on targeted drug delivery nanoparticles present a promising approach to addressing the challenges presented by triple-negative breast cancer (TNBC). TNBC is an aggressive subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors, restricting the effectiveness of targeted therapies and traditional hormone therapies. Comprehending the creation of protein corona is essential as it has the potential to greatly change the biological makeup and behavior of nanoparticles, affecting their biodistribution and targeting effectiveness. In the same way, aggregation research is essential in order to prevent possible issues with nanoparticle functionality and stability in biological settings. Our project involves the synthesis of PLGA (poly (lactic-co-glycolic acid)) nanoparticles that are equipped with two key components: EGFR (epidermal growth factor receptors ) targeting antibodies and PEG (polyethylene glycol) ligands. The EGFR-targeting antibodies are specifically designed to recognize and bind to EGFR that are overexpressed on the surface of TNBC cells, thereby improving the precise targeting of these cancer cells. On the other hand, PEG ligands are included to increase the nanoparticles' circulation time in the bloodstream and help them evade detection and clearance by the immune system. It's critical to distinguish between these two roles: although PEGylation, addition of PEG ligands, increases the duration of the nanoparticles' circulation, it does not guarantee that the particles will more efficiently target and aggregate in the intended tissues or cells. Therefore, to guarantee that the nanoparticles can successfully carry medications to TNBC cells, both the targeting capability offered by the EGFR antibodies and the extended circulation attained by PEG ligands must be adjusted separately. Using nanoparticle tracking analysis (NTA) and cross-polarization techniques, we aim to measure the size, viscosity, and aggregation behavior of these nanoparticles. This innovative approach seeks to optimize ligand combinations for improved nanoparticle stability and delivery efficacy. Developing a thorough understanding of how protein corona formation and aggregation affect our nanoparticle formulations will help us create more effective treatment plans for TNBC, which could result in important progress in the treatment of this challenging cancer subtype.
Project Title: Uterine Cancer Image Analysis with Convolutional Neural Networks
REU Scholar: Mason Brown (NJIT), Advisor: Joshua Young, Nellone Reid, Mentors: Daniel Mottern and Mo Li
Abstract: Endometrial cancer is a deadly disease that affects thousands of women each year, with a disproportionate mortality rate in black women compared to other racial groups. This discrepancy can be partially credited to the fact that it is often diagnosed in a later, less treatable stage in black women. A certain portion of this diagnostic differential can be explained by human bias and errors. Artificial intelligence and machine learning (AI/ML) can be used to compensate for this human element. Convolutional neural networks (CNNs) are an advanced form of ML that has shown promise in medicine, accurately performing diagnoses and medical image analysis. A key advantage of CNNs is that they require less manual image preprocessing compared to other ML techniques. The main issue with CNNs is that they require immense datasets to be trained from scratch, but repurposing pre-trained CNNs and artificially expanding the dataset cut down the required data collection. This study uses pre-trained CNNs to distinguish images of different types of uterine cancer and different racial groups and evaluate those models for racial biases. Exploring the capabilities of AI/ML for diagnostic purposes allows for the minimization of human biases, potentially saving lives and improving care.
Project Title: Targeted Delivery of Platinum Nanoparticles for Triple-Negative Breast Cancer Treatment
REU Scholar: Enakeno Akpokene (Mercy University), Advisor: Kathleen McEnnis, Mentor: Ashish Kokkula
Abstract: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors. This lack of receptors renders conventional hormonal therapies and HER2-targeted treatments ineffective, resulting in a poorer prognosis and limited therapeutic options. Current treatments, such as chemotherapy, often inflict severe side effects and resistance due to their non-specificity in targeting cells, causing toxic effects on patients. This underscores the urgent need for novel treatment strategies. This study aims to explore the potential of platinum nanoparticles (Pt NPs) as a targeted delivery system for TNBC treatment. Pt NPs could offer more precise therapy with reduced side effects and increased efficiency compared to traditional treatments. The Pt NPs will be modified with PEG and PLGA to enhance circulation time and safety. They will also be functionalized with targeting ligands specific to TNBC cells, such as the epidermal growth factor receptor (EGFR), to target TNBC cells accurately. In vitro studies will evaluate the uptake efficiency, cytotoxicity, and efficacy of the Pt NPs to demonstrate their specificity and efficacy in targeting TNBC cells. The targeted delivery is expected to reduce off-target effects, thereby minimizing chemotherapy side effects and addressing drug resistance, potentially leading to improved patient outcomes. Future in vivo studies will assess biodistribution and long-term therapeutic effects, potentially advancing TNBC treatment and improving patient outcomes.
Project Title: Estimation of Dermal Absorption of Chemical Agents Using Physiologically-Based Pharmacokinetic Models
REU Scholar: Daniel Gendy (NJIT), Advisor: Amir Miri, Nellone Reid, Mentor: Mohaddeseh Mohammadi
Abstract: Microfluidic devices are often used instead of animal models for disease modeling due to their low cost and potential for human cell integration. Previous work has been done to fabricate microfluidic devices using Polydimethylsiloxane (PDMS), but this is an often time consuming, laborious, and expensive process. There is thus a need to create inexpensive microfluidic platforms for disease screening, progression, and modeling. Here, we report a double layer parafilm microfluidic platform with a total fabrication time of 20 minutes. A laser cutter is used to create microchannels while leaving a bottom parafilm layer intact. This glass + parafilm + glass microfluidic setup is heated at 60 °C for 20 minutes on a hotplate, and a styrofoam box is placed on top of the microfluidic device to add 20kPa of uniform static pressure to enhance parafilm adhesion and prevent leakage. Inlet and outlet holes are drilled into the top glass slide using diamond drill bits, and tube connectors are superglued to both openings to allow for flow. Future work must be done to seed inlets with human mesenchymal stem cells to study their differentiation into endothelial cells under shear stress and their adherence to the inner lining of the parafilm channel.
Project Title: Reactor Design for Miniature Peptide Reactor
REU Scholar: Theon Harry (Mercy University), Advisor: Nellone Reid, Mentor: Alexandria Griffith Ruiz
Abstract: A peptide synthesizer sequences amino acids into peptides by deprotecting and protecting amino acids, but this process generates large amounts of hazardous waste (e.g., dimethylformamide, diethyl ether) and is very expensive ($90,000). This research addresses the urgent need for a more practical and cost-effective solution by focusing on the development of a reactor vessel for a miniature peptide synthesizer. The goal of this project is to design and construct a compact, efficient, and affordable reactor vessel that simplifies peptide synthesis, making it more accessible for a wider range of laboratories and applications. The construction of the reactor vessel involves several significant challenges. These include ensuring uniform mixing and temperature control within a micro-scale environment, preventing cross-contamination between synthesis cycles, and maintaining the structural integrity of the vessel under repeated use. Our research methods integrate principles of chemical engineering, microfluidics, and materials science. Specifically, employing techniques such as computational fluid dynamics for optimizing flow and 3D design for precise microfluidic channel fabrication. The experimental design focuses on optimizing the reactor’s geometry and material selection to enhance chemical reactions and minimize any potential for leaks or blockages. Prototype development is underway, with initial testing to ensure the reactor vessel can withstand repeated trials with various viscous liquids and solvents. The anticipated outcomes of this project include the successful development of a reactor vessel that not only improves peptide synthesis but also highlights significant advancements over traditional methods. These improvements include reduced reagent consumption and lower overall costs. Moreover, the compact and robust design of the reactor vessel is expected to enhance its practicality and flexibility in diverse environments. Future work will focus on refining the reactor vessel to improve its durability and efficiency, as well as exploring its scalability for commercial production. The goal is to make peptide synthesis more accessible, thus accelerating advancements in scientific research and industrial applications.
Project Title: Wearable Piezoelectric Fingers for Tumor Detection
REU Scholar: Isabella Frangiosa (Rowan University), Advisor: Lin Dong, Mentor: Sun Kwong
Abstract: Abstract: Breast cancer is the most common cancer in America, making up 30% of all newly diagnosed cases each year. Breast tumor size and spread are used to diagnose cancer mainly through mammograms. Although women over the age of 40 can regularly get mammograms, younger women often face high costs due to lack of insurance coverage when attempting to get screened. A cheap, portable screening method for breast tumors that can be performed independently will increase early cancer detection and lower mortality rates. Piezoelectric polymers, which generate charge in response to mechanical stress, have much potential for sensing applications due to their excellent flexibility and ability to be self-powered. Electrospinning the polymer results in highly piezoelectric, flexible nanofibers that can be fabricated into a battery-free sensor for biomedical applications. Through harnessing the piezoelectric effect, a nanofibrous sensor can be developed to measure the elastic modulus of tissue since breast tumors and healthy breast tissue have reported elastic moduli of approximately 10 kPa and 800 Pa respectively. Conventional tests with materials of different stiffness and constant applied force were performed to correlate the device’s output voltage with material stiffness. Future work will optimize device design and incorporate circuitry to eliminate operator dependance.
Project Title: A Modeling Framework for Simulating Skin Decontamination of Chemical Warfare Agents
REU Scholar: Julie Mena (Bergen Community College), Advisor: Laurent Simon
Abstract: According to the World Health Organization, 2 million people died due to exposure to toxic chemicals (TCs) such as lead, pesticides, and occupational carcinogens in 2019 alone. Ordinary people can come in contact with TCs through work environments such as production workers in the pharmaceutical industry and agriculture, contaminated water, and products such as cosmetics, household cleaners, and gasoline. Long-term exposure to TCs can cause cancer, organ failure/damage, or a compromised immune system. Continuous exposure to benzene can cause haematotoxicity that can lead to an increased risk of leukemia as well as gastrointestinal and neurological toxicity. Benzene is found in petroleum-derived products such as synthetic rubbers, polyesters, paint thinners, and gasoline. It is also used in pharmaceuticals, explosives, and herbicides. To protect the lives of employees who risk high exposure, we use a physiologically based pharmacokinetic (PBPK) model and mathematical simulations to determine the accumulation of benzene in the bloodstream over an average work schedule and to understand the consequences of changing variables like concentration level and exposure time on the accumulation of TCs in the bloodstream. We can determine from the results whether the work schedule exceeds benzene's toxic level, effective decontamination methods, and ways to mitigate exposure.
Project Title: Piezoelectric Needle for Guided Tissue Targeting
REU Scholar: Natalia Narvaez (UT San Antonio), Advisor: Lin Dong, Mentor: Mengdie Sun
Abstract: With the rise of cancer-related deaths, biopsy procedures have become crucial for diagnosis, treatment response, and guiding therapy. Needles for biopsies of tumor tissue can be guided by ultrasound or CT. However, these methods have limitations, including limited accuracy and utility with smaller lesions, human error, wrongful needle placement, radiation exposure, and the risk of accidental spread of cells, leading to false negatives and poor tissue samples. Healthy and diseased tissues exhibit differences in mechanical properties, with healthy tissue typically having lower stiffness and tumorous tissues being more rigid. Cancerous tissue can significantly alter the mechanical properties of the surrounding tissue, which can be quantified using Young's modulus to distinguish between healthy and diseased tissues. This approach involves a piezoelectric needle-shaped device, which leverages the piezoelectric effect to generate an electric charge due to mechanical stress, enabling precise targeting of tumor tissue. The device aims to measure tissue stiffness accurately to distinguish between healthy and cancerous tissues, addressing limitations of traditional biopsy methods such as limited accuracy and human error. The ultimate goal is to create a more accurate and less invasive method for cancer diagnosis, improving the characterization of disease states and assisting in the progression monitoring of cancer.
Project Title: Modeling a Small-Scale Peptide Synthesizer
REU Scholar: Brianna Reed (Alcorn State University), Advisor: Nellone Reid, Mentor: Alexandra Griffith
Abstract: Automated peptide synthesizers are widely used in the industry of pharmaceutics. Peptide synthesizers revamped medicinal chemistry by increasing productivity in the development of peptide drugs, reducing errors in peptide synthesis, and increasing research throughput. Most synthesizers perform solid-phase peptide synthesis (SPPS). Although large scale peptide synthesizers can synthesize lengthy chains of amino acids, there are still disadvantages. These synthesizers are expensive, not portable, and produce massive amounts of hazardous waste. The waste components consist of dimethylformamide (DMF), piperidine, oxyma, acetic anhydride, etc. This project aims to fabricate a small-scale automated peptide synthesizer. Thus, this synthesizer will be affordable and portable. My objective is to create an efficient waste disposal system for the miniature synthesizer. Computer-aided design software such as AutoCAD and Fusion360 are being utilized to make this waste disposal system. The proposed design for the waste disposal system is an elastic nylon balloon. Since the waste balloon will be in the inner workings of the synthesizer, a mechanism has been established to ensure the removal of the balloon in the safest manner. The proposed mechanism is a drawer for the waste disposal balloon. This will be advantageous when considering the removal of the waste balloon from the synthesizer. The expected results will include the balloon attached to an O-ring, embedded in the drawer, which will be directly connected to the waste valve in the synthesizer.
Project Title: Specific Cancer Biomarker Detection Using the ESSENCE Biosensor Platform
REU Scholar: Sariah Coleman (Alcorn State University), Advisor: Sagnik Basuray, Mentor: Niranjan Haridas
Abstract: Cancer is a leading cause of death worldwide. Early detection plays a crucial role in preventing the progression of the disease and stopping its spread. Electrochemical Biosensor biomarker-based identification is becoming increasingly recognized as a high viable approach for the early detection of various ailments. The current state of biosensors is hindered by two significant challenges: limited sensitivity and insufficient selectivity. In this work, we are using ESSENCE, an Electrochemical Sensor that uses a Shear-Enhanced, flow-through Nanoporous Capacitive Electrode, to detect cancer biomarkers. Nestled between a top and bottom micro electrode, ESSENCE is a microfluidic channel loaded with transducer material. This electrochemical approach to biosensing has four notable advantages over the current generation of biosensors: improved sensitivity, better SNR, reduced diffusion limitations, and customizable selectivity. The goals of this project are to optimize the ESSENCE sensor to detect biomarkers like the tumor protein p53 and human epidermal growth factor receptor 2 (HER2) and to ensure real-world applicability through validation against standard methods (blotting, PCR, electrophoresis). Through the precise identification of cancer biomarkers and accurate validation, the sensor has the potential to improve early detection, facilitate tailored treatment, and aid in continuous monitoring. This could result in more efficient disease management.
Project Title: EGFr Binding Peptide Contrast Agents for Signaling EGFr-Positive Tumors
REU Scholar: Mimi Pham (NJIT), Advisor: Vivek Kumar Mentor: Joseph Dodd-o
Abstract: Triple Negative Breast Cancer, TNBC, is an aggressive and fast-growing subtype of Breast Cancer, which lacks an established therapeutic target. It is characterized by the absence of increased expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). TNBC affects 13 in every 100,000 women in the United States. Magnetic Resonance Imaging, MRI, is the main noninvasive method to detect these tumors. However, due to TNBC’s unique characteristics and nonuniform shape, it is more likely to have inaccuracies in the diagnosis of the tumor and/or tumor morphology. A gadolinium-based contrast agent chelated by an Epidermal Growth Factor Receptor (EGFr) binding peptide is being developed to address these limitations in MRIs. The use of this conjugate will improve the contrast in MRI scans, leading to more accurate detections of EGFr-positive tumors, such as the most common subtypes of TNBC. The conjugate will bind to EGFr, where the paramagnetic gadolinium ions will interact with water molecules in tissues, influencing relaxation rates on MRI scans. EGFr-binding peptides were synthesized by Solid-Phase Peptide Synthesis and coupled with a chelating agent. The main peptide, AEGFr, was found in previous literature and was linked to self-assembling peptides previously developed in KumarLab to develop novel self-assembling multidomain peptides K1-G-AEGFr and E1-G-AEGFr. The peptide conjugates were synthesized and characterized for their chemical, structural, and mechanical properties. The affinity of self-assembling conjugated peptides to the EGFr needs to be further tested with Microscale Thermophoresis, MST to find the best binding affinity. Next, the peptide conjugates are combined with a gadolinium(III) ion solution. The peptide will then self-aggregate to form a translucent soft hydrogel. The formed EGFr Binding Peptide Contrast Agent can then be injected into a patient, increasing the accuracy of EGFr+ tumor diagnosis.
Project Title: Effect of Electromagnetic Field Exposure to T47D Cells in a Microfluidic Device
REU Scholar: Eduard Stoyko (NJIT), Advisors: Nellone Reid, Amir Miri, Sagnik Basuray, Mentor: Swaprakash Yogeshwaran
Abstract: Invasive treatments for cancer such as chemotherapy, drugs, and surgery are shown to have severe side effects such as toxicity to healthy cells, and long recovery times. Furthermore, their effectiveness is limited in preventing metastases and are further restricted by their high cost. Because of this, a non-invasive and more effective treatment for cancer is highly desirable to discover. In previous work it has been shown that electro-magnetic fields have a negative effect on a variety of cancer cells (including T47D breast cancer cells), while having a minimal effect on healthy cells (such as MCF-10A healthy breast cells). This paper will demonstrate the effect a static magnetic field has on T47D cells by showing a transient effect on cell life through time and comparing that to the effect on MCF-10A cells. This was done by generating a magnetic field through a helmholtz coil of varying intensities, placing the cells within the range of the coil, and imaging the cells throughout a 4-hour time frame. Furthermore, in order to show the additional effects of electromagnetic fields when used in conjunction with other treatments, 17-? Estradiol will be applied to the cell media and monitored over time. This will then be placed in a hydrogel based microfluidic device to further demonstrate the effects in a more realistic environment. We have successfully conducted this experiment and have observed that there is no effect of EMF on cell life in a short time span, when both conducted in isolation, and when in an additional heated environment. Future research can be conducted to refine the field strength and measure the metabolic rate of the cells while in the field, as well as test other drugs and treatments that can show an increased effectiveness.
Project Title: Real-time Monitoring of Extracellular Matrix Remodeling During Breast Cancer Progression
REU Scholar: Gabrielle Uskach (NJIT), Advisor: Amir Miri, Mentor: Aydasadat Pourmostafa
Abstract: The metastatic cascade begins with migration of the tumor cells from the primary site and intravasation into blood or lymph vessels. This involves complex biological processes, including the epithelial-mesenchymal transition for migration and matrix degradation for intravasation. Current methods for screening tumor malignancy involve biopsies, which are invasive, expensive, and detrimental to a patient’s health. The local microenvironment of a cell, the extracellular matrix (ECM), has specific biomechanical properties that are key steps in the metastatic cascade of the tumor and its response to therapy. The design of a three-dimensional hydrogel-based ECM would monitor physical changes during breast cancer cell migration and progression, determining tumor malignancy noninvasively. This research will utilize hydrogels with varying ECM composition to study how ECM stiffness, topology, and protein deposition changes during ECM remodeling of the MDA-MB-231 aggressive breast cancer tumor model. With 3D organoid models there will be an increased surface area to reduce the noise for personalized medicine approaches. Electrochemical analysis and mechanical testing will be utilized for real-time monitoring of the cell-associated changes in matrix stiffness, degradability, and porosity. Through monitoring of the ECM remodeling, the aim is to develop noninvasive real-time monitoring techniques for cancer progression diagnosis. Abstract: Electrospun PVDF Nanofibers for Early Cancer Detection via Acoustic Wave Sensing.