Nanomedicine Commons^™

Magnesium-Based Metal Matrix Nanocomposite Implants And Nanobubble-Based Delivery Systems: Integrated Strategies For Bone Loss Treatment With Cytocompatibility Evaluation, Lucas José Martinho Bizuti

Honors Undergraduate Theses

This thesis intends to investigate the development of different multimodal therapeutic strategies for combating bone loss. Most specifically, this paper will emphasize the utilization of Magnesium-Based Metal Matrix Nanocomposite Implants (MMNC) and Nanobubble-Based Delivery Systems as options for future treatment focus. The effects of biodegradable magnesium implants were evaluated for cytotoxicity and cytocompatibility via Hematoxylin and Eosin, and Masson’s Trichrome staining, as well as radiological images. The Nanobubble-Based Delivery System is being developed and optimized as a delivery system to target osteoclast activity. This paper focused on optimizing experimental parameters, which include Rotational speeds for nanobubble stimulation under microgravity conditions …

Investigating The Immunostimulatory Potential Of Dsrna-Silk Nanoparticle Complexes In Melanoma, Samuel J. Peters

Theses and Dissertations (Comprehensive)

The rate of resistance to immune checkpoint inhibitor treatment in metastatic melanoma is quite high, with an overall rate of 70%. Melanoma achieves these high rates of resistance by suppressing the immune response in the tumour microenvironment (TME), making them immunologically “cold”. The type 1 interferon response could be leveraged to initiate immune responses in melanoma, making their “cold” TMEs “warm” again. Double-stranded ribonucleic acids (dsRNAs) are potent activators of an innate immune response; however, they are susceptible to degradation by nucleases present in the body and need a carrier. Silk nanoparticles (SNPs) are an ideal drug-delivery platform as they …

Biomechanics Of The Atherosclerotic Lipidome: (Un)Expected Statin Interactions And Membrane Remodelling, Ethan M. Fong

Pomona Senior Theses

Statins interact with lipid membranes in ways that shape their pharmacokinetics, off-target effects, and pleiotropic actions, yet these interactions' mechanical and biophysical consequences remain poorly understood. This thesis employs a combination of surface plasmon resonance (SPR), quartz crystal microbalance with dissipation monitoring (QCM-D), and rheological modelling to characterize how representative statins intercalate within biomimetic supported lipid bilayers (SLBs) of healthy and diseased composition. SPR reveals that lipophilic statins exhibit higher apparent affinities and slower dissociation kinetics, especially in cholesterol- and anionic lipid-rich membranes. QCM-D analyses demonstrate that statins alter membrane mass, dissipation, and interfacial stiffness in a statin- and membrane-dependent …

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 …

Studying The Role Of Novel Carbon Nano Tubes As A Therapeutic Agent To Treat Triple Negative Breast Cancer (Tnbc) - An In Vitro And In Vivo Study, Kamal Asadipour, Narendra Banerjee, Jazmine Cuffee, Karrington Perry, Shennel Brown, Anasua Banerjee, Erik Armstrong, Stephen Beebe, Hirendra Banerjee

Bioelectrics Publications

Triple Negative Breast Cancer (TNBC) is a malignant cancer with a very high mortality rate around the world. African American(AA) women are 28% more likely to die from triple-negative breast cancer (TNBC) than white women with the same diagnosis. AA patients are also more likely to be diagnosed at a later stage of the disease and have the lowest survival rates for any stage of diagnosis; There are very few existing anti TNBC drugs with therapeutic efficacy hence newer anti TNBC drug design and investigation is needed. Carbon Nano Tubes(CNT) in recent years have shown effective anti-cancer properties in various …

Elucidating Mechanisms Of Enhanced Dsrna-Nanophytoglycogen Innate Immune Responses In Healthy Human Cells, Nicholas Jadaa

Theses and Dissertations (Comprehensive)

Immunostimulatory nucleic acids, such as long double-stranded RNA (ds)RNA, can stimulate innate immune responses in a non-sequence specific manner. These molecules are recognized by pattern-recognition receptors in the cytoplasm, endosome, and on the cell surface. Activation leads to the production of mediators of innate immune pathways, including type I interferon and proinflammatory cytokines. Although these receptors are present in all cells, their role in non-immune cells is often overlooked due to their lower level of responsiveness. Nanocarriers can enhance these nucleic acid-mediated responses, allowing for exploration of innate immune pathways in non-immune cells. Nanoparticles as carriers of nucleic acids can …

Development Of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Ana Martinez Bulnes, Nirnoy Dan, Subhash C. Chauhan, Sheema Khan, Murali M. Yallapu

Research Colloquium

Introduction: About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in other cancers but limited response in pancreatic cancer due to desmoplasia and fibrotic tumor microenvironment. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. Due to its high membrane expression, MUC13 may serve as an excellent target …

Protein L Functionalized Microparticles For Early Detection Of Surface Markers In Heterogeneous Colorectal Lesions, Saleh Ramezani

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths among both men and women worldwide, a statistic that can be improved with early detection. Increased understanding of the tumor landscape has identified surface antigens that can be utilized to distinguish normal and cancerous tissue lining the colonic lumen. Use of antibodies conjugated to nano/micromaterials offers a means to detect these antigens, however, the heterogeneous nature of tumors makes it unlikely that antibodies against a single antigen will have sufficient sensitivity and specificity to detect all tumors. A versatile micromaterial able to be functionalized with more than one targeting …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Tumor-Targeted Ph-Sensitive Manganese Oxide Nanoparticle For Enhanced Detection Of Breast Cancer Using Mri, Celia Martinez De La Torre

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the United States, approximately 287,850 new cases of invasive breast cancer will be diagnosed, and over 43,000 women will die because of it in 2022. Currently, mammography is the gold standard for breast cancer surveillance. Although this detection technique is relatively cheap and fast, it misses about 1 in 5 breast cancers in younger women with dense breast tissue, causing a delay in treatment. Compared to mammography, magnetic resonance imaging (MRI) has superior soft-tissue contrast that elucidates structural differences within soft tissue to detect more breast cancers. However, MRI still misses

NEMO particles were produced by synthesizing manganese oxide …

Comparison Of Free Versus Encapsulated Drugs On 3t3 Differentiation, Simon H. Friedrich, Gabriel Volpe

UROP Posters

The scope of this project was to design, synthesize and test targeted nanoparticles containing hydrophobic and hydrophilic drugs that promote browning in adipose tissue. For hydrophilic drugs the use of liposomes and their hydrophilic core is more useful than the PLGA nanoparticles which have hydrophobic cores. The inhibition of the FOXO1 pathway and modulation of autophagy in adipose tissue can promote browning of white adipose tissue, or an energy burning state where excess energy is burned as heat instead of stored in the cell. If successful, these drugs would offer an alternative treatment for obesity where changes to the patient's …

Intracellular Trafficking And Distribution Of Cd And Inp Quantum Dots In Hela And Ml-1 Thyroid Cancer Cells, Min Zhang

Graduate Theses/Dissertations

The study of the interaction of engineered nanoparticles, including quantum dots (QDs), with cellular constituents and the kinetics of their localization and transport, has provided new insights into their biological consequences in cancers and for the development of effective cancer therapies. The present study aims to elucidate the toxicity and intracellular transport kinetics of CdSe/ZnS and InP/ZnS QDs in late-stage ML-1 thyroid cancer using well-tested HeLa cells as a control. The XTT viability assay showed that ML-1 cells, and non-cancerous mouse fibroblast cells, exhibit no viability defect in response to these QDs, whereas HeLa cell viability decreases. These results suggest …

Synthesis, Characterization And Applications Of Peptide-Coated Nanoparticles, Mina Sadat Poursharifi

Dissertations, Theses, and Capstone Projects

Ovarian Cancer (OC) is the most lethal female malignancy worldwide, mainly due to its high recurrence rate and poor diagnosis. Most patients present with late stage of the disease, and less than 25% of patients survive the five years mark. Nanotherapy provides significant and unique benefits for drug efficacy, as nanoparticles (NPs) can increase the solubility, bioavailability, and permeability of many potent drugs. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful biodegradable polymers used in NPs formulations, mainly due to its biocompatibility and biodegradability. Polyethylene glycol (PEG) is one of the most commonly used moieties to prolong the NPs …

Impact Of Angiogenic And Osteogenic Factors In The Presence Of Biodegradable Piezoelectric Films, Jayla Millender

University Scholar Projects

One of the most common causes of bone graft rejection is lack of a vascular network connecting the graft to the existing native tissue – allowing for nutrient flow. Under current grafting techniques, the existing blood vessel network in the patient slowly invades the implant in order to supply the injured site with its necessary nutrients. The purpose of this research is to determine if a synthetic bone graft with a stable microvascular network can be developed in vitro. I hypothesize that the use of indirect angiogenic factors such as sonic hedgehog homolog and hypoxia-inducible factor-1 in combination with the …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)₅C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl₃ with [(WR)₅C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR) …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer, Sumit Mukherjee

Dissertations, Theses, and Capstone Projects

Glioblastoma (GBM) is one of the most deadly forms of cancer with a mean 5-year survival rate of ≤5%. We have used the non-invasive strategy of long-term intranasal (IN) delivery of a glioblastoma-directed adduct of curcumin (CC), CC-CD68Ab, into the brain of murine GBM cell line GL261-implanted mice to study the therapeutic effect of CC on GBM remission. The treatment caused GBM tumor remission in 50% of GL261-implanted GBM mice. A similar rescue rate (60%) was also achieved through long-term intraperitoneal (i.p) infusion of a highly bioavailable phosphotidylcholine (PC)-encapsulated formulation of CC, Curcumin Phytosome Meriva (CCP), into the GL261-implanted GBM …

Nucleic Acid Combinations: A New Frontier For Cancer Treatment, K. C. Remant Bahadur, Bindu Thapa, Juliana Valencia-Serna, Hamidreza Montazeri Aliabadi, Hasan Uludağ

Pharmacy Faculty Articles and Research

The emerging molecular understanding of cancer cell behavior is leading to increasing possibilities to control unchecked cell growth and metastasis. On the other hand, development of multifunctional drug carriers at the ‘nano’-scale is providing exciting new therapeutic strategies in clinical management of cancer beyond the conventional cytotoxic drugs. A new frontier in this regard is the combinational use of complementary agents based on nucleic acids to overcome the limitations of conventional therapy. The existence of tightly-integrated cross-talk through multiple signaling and effector pathways has been appreciated for some time, and the plasticity of such a network to overcome one-dimensional intervention …

The Effect Of K562-Il21-2 Plasma Membrane Particles On The Proliferation Of Natural Killer Cells To Fight Cancer, Michelle Prophete

Honors Undergraduate Theses

Immunotherapy has emerged as a current and future paradigm of cancer treatment, which utilizes the body’s immune system to eradicate cancer. Natural Killer (NK) cells as part of the innate immune system have immense potential in their anti-tumor cytotoxic activities and host cell surveillance properties. NK cells comprise approximately five to fifteen percent of peripheral blood lymphocytes and can be proliferated in vitro using recently developed methods with co-cultures with feeder cells (derived from engineered tumor cells) or plasma membrane (PM) particles, produced from the fore mentioned feeder cells, in combination with soluble cytokines. For efficient growth and maintenance of …

Selective Anticancer Activity Of Hydroxyapatite/Chitosan-Poly(D,L)-Lactide-Co-Glycolide Particles Loaded With An Androstane-Based Cancer Inhibitor, Nenad Ignjatović, Katarina M. Penov-Gaši, Victoria M. Wu, Jovana J. Ajduković, Vesna V. Kojić, Dana Vasiljević-Radović, Maja Kuzmanović, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. ¹H NMR and ¹³C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the …

Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross Verheul, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA and …

Synthesis And Characterization Of Nanoparticle-Coupled Proteins In Human Serum Albumin, Kyle M. Mahoney

Honors College Theses

Recently, cancer has become an ever-growing issue and has led to many researchers attempt to unravel the mystery of the disease. This research has led to a promising field of treatment: nanotechnology-coupled pharmaceuticals. Nanoparticles act as a whole unit when in conjugation with other molecules and add to the carrier molecule, most often proteins, benefits the nanoparticles themselves possess. One such carrier protein that can be conjugated with nanoparticles is Human Serum Albumin (HSA). Albumin is of interest in cancer research for two reasons: it is native to the human vasculature so it does not elicit immunological reactions, and it …

Mechanisms Of Nanosecond Pulsed Electric Field (Nspef)-Induced Cell Death In Cells And Tumors, Stephen J. Beebe

Bioelectrics Publications

The evolution of pulse power technology from high power physics to biology and medicine places nanosecond pulsed electric fields (nsPEFs) in positions for in vitro and in vivo applications as non-ligand agonists that not only bypass plasma membrane receptors for induction of intracellular signaling pathways, but also bypass intracellular oncogenic impasses to induce cell death by regulated mechanisms. Based on work reviewed here, a likely scenario for cell and tumor demise includes nsPEF-induced permeabilization of the plasma membrane, Ca2+ influx, dissipation of the mitochondrial membrane potential, which is likely due to events beyond permeabilization of the inner mitochondrial membrane, cytochrome …

Engineered Plga Nanoparticles For Delivery Of Sirna In Mcf-7 Breast Cancer Cells, Sydney Pong, Samit Shah, Vivek Gupta

Student Scholar Symposium Abstracts and Posters

Small interfering RNAs have been an emerging medical treatment for molecular based diseases as they are capable of gene-specific knockdown. Appropriate and efficient delivery remains one of the biggest challenges in the development of siRNA as an anti-cancer treatment. Nanoparticles containing siRNA were characterized and the efficacy of various peptides in the transfection of the nanoparticles were tested. A gene silencing assay was developed in order to determine the effect of siRNA therapeutics on gene functionality in breast cancer cells.

Nanosecond Pulsed Electric Field (Nspef) Ablation As An Alternative Or Adjunct To Surgery For Treatment Of Cancer, Ru Chen, Xinhua Chen, Stephen J. Beebe

Bioelectrics Publications

Surgery as resection or transplantation remains a fundamental means for cancer treatment and often offers an opportunity for a cure. However, surgery is not always possible because of tumor proximity to blood vessels or ducts or when a patient is not healthy enough to undergo surgery. Application of nanosecond pulsed electric fields (nsPEFs) is a new approach to treat cancer using pulse power technology that was originally designed for military purposes. This novel approach deposits extremely short pulses of high power, low energy electric fields into malignant tissues using electrodes to encompass tumors. Pre-clinical studies show that treatments are effective …