Clinical application of anticancer drugs is mostly limited due to their hydrophobic nature, which often results in lower bioavailability and lesser retention in systemic circulation. Despite extensive research on the development of targeted drug delivery systems for cancer treatment, delivery of hydrophobic therapeutic drugs to tumor cells remains a major challenge in the field. To address these concerns, we have precisely engineered a new hyperbranched polymer for the targeted delivery of hydrophobic drugs by using a malonic acid-based AB monomer and 1,6-hexanediol.
View Article and Find Full Text PDFElucidating the underlying principles of amyloid protein self-assembly at nanobio interfaces is extremely challenging due to the diversity in physicochemical properties of nanomaterials and their physical interactions with biological systems. It is, therefore, important to develop nanoscale materials with dynamic features and heterogeneities. In this work, through engineering of hierarchical polyethylene glycol (PEG) structures on gold nanoparticle (GNP) surfaces, tailored nanomaterials with different surface properties and conformations (GNPs-PEG) are created for modulating the self-assembly of a widely studied protein, insulin, under amyloidogenic conditions.
View Article and Find Full Text PDFFrequent outbreaks of food-borne pathogens, particularly O157:H7, continue to impact human health and the agricultural economy tremendously. The required cell count for this pathogenic strain of O157:H7 is relatively low and hence it is vital to detect at low colony forming unit (CFU) counts. Available detection methods, though sensitive, fall short in terms of timeliness and often require extensive sample processing.
View Article and Find Full Text PDFIncreasing foodborne illnesses have led to global health and economic burdens. O157:H7 is one of the most common disease-provoking pathogens and known to be lethal Shiga toxin-producing (STEC) strains. With a low infection dose in addition to person-to-person transmission, STEC infections are easily spread.
View Article and Find Full Text PDFInfection with the Zika virus (ZIKV) is an ongoing problem especially as accurate, cost-effective testing remains unresolved. In addition, coinfection occurs with both the Dengue virus (DENV) and ZIKV which leads to cross-reactivity between the flaviviruses and can result in false positives and inaccurate testing. This supports the current need for a simple assay that can detect Zika antibodies sensitively that at the same time can differentiate between cross-reactive antibodies.
View Article and Find Full Text PDFNon-Small-Cell Lung Cancer (NSCLC) has gained resistance to common chemo- and radiotherapy due to the oncogenic K-RAS mutations. In this work, lactonic sophorolipids (LSL), a constituent of natural sophorolipids known to inhibit histone deacetylase (HDAC) activity, is used to evaluate its potential anticancer property for the treatment of NSCLC. In addition, ganetespib (GT), a Hsp90 inhibitor, is used for its known antitumor activity in several K-RAS mutant NSCLC cells.
View Article and Find Full Text PDFViral fusion is a critical step in the entry pathway of enveloped viruses and remains a viable target for antiviral exploration. The current approaches for studying fusion mechanisms include ensemble fusion assays, high-resolution cryo-TEM, and single-molecule fluorescence-based methods. While these methods have provided invaluable insights into the dynamic events underlying fusion processes, they come with their own limitations.
View Article and Find Full Text PDFIn this study, a new hyperbranched polyester copolymer was designed using a proprietary monomer and diethylene glycol or triethylene glycol as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by p-tolulenesulfonic acid. The progress of the reaction was monitored with respect to time and negative pressure, with samples being subjected to standard characterization protocols.
View Article and Find Full Text PDFBackground & Aims: Prolactin (PRL) signaling is up-regulated in hormone-responsive cancers. The PRL receptor (PRLR) is a class I cytokine receptor that signals via the Janus kinase (JAK)-signal transducer and activator of transcription and mitogen-activated protein kinase pathways to regulate cell proliferation, migration, stem cell features, and apoptosis. Patients with pancreatic ductal adenocarcinoma (PDAC) have high plasma levels of PRL.
View Article and Find Full Text PDFDetection of bacterial contaminants in blood and platelet concentrates (PCs) continues to be challenging in clinical settings despite available current testing methods. At the same time, it is important to detect the low bacterial contaminants present at the time of transfusion. Herein, we report the design and synthesis of a dual-modal magneto-fluorescent nanosensor (MFnS) by integrating magnetic relaxation and fluorescence modalities for the wide-range detection of blood-borne pathogens.
View Article and Find Full Text PDFThis Article contains an error in Figure 6. In panel b, the left-hand image is mistakenly described as showing fluorescence before treatment, while it in fact shows the same white light image as the right-hand panel without fluorescent overlay to better visualize the tumour location. A correct version of Figure 6b is presented in the accompanying Author Correction.
View Article and Find Full Text PDFK-RAS is the most common mutated oncogene associated with Non-Small-Cell Lung Cancer (NSCLC). So far, there are no promising chemotherapies for the direct inhibition of K-RAS, and considered to be undruggable. In this work, we have introduced a new platinum-based cyanoximate complex, Pt(MCO) as an anti-cancer drug to enhance the therapeutic efficacy of Hsp90 inhibitor drug, ganetespib for the combination therapy of NSCLC.
View Article and Find Full Text PDFBackground: Engineered inorganic nanoparticles (NPs) are essential components in the development of nanotechnologies. For applications in nanomedicine, particles need to be functionalized to ensure a good dispersibility in biological fluids. In many cases however, functionalization is not sufficient: the particles become either coated by a corona of serum proteins or precipitate out of the solvent.
View Article and Find Full Text PDFEach year, infectious diseases are responsible for millions of deaths, most of which occur in the rural areas of developing countries. Many of the infectious disease diagnostic tools used today require a great deal of time, a laboratory setting, and trained personnel. Due to this, the need for effective point-of-care (POC) diagnostic tools is greatly increasing with an emphasis on affordability, portability, sensitivity, specificity, timeliness, and ease of use.
View Article and Find Full Text PDFIdentifying new druggable targets is desired to meet the needs for effective cancer treatments. To this end, we previously reported the efficacy of a therapeutic peptide called CT20p that displays selective cytotoxicity through inhibition of a multi-subunit, protein-folding complex called Chaperonin-Containing TCP-1 (CCT). To investigate the role of CCT in cancer progression, we examined protein levels of CCT subunits in liver, prostate, and lung cancer using human tissue microarrays.
View Article and Find Full Text PDFIn this study, we have synthesized a new hyperbranched polyester polymer containing sulfur-pendants (HBPE-S) in the branching points. This HBPE-S polymer is composed of spherical shaped, aliphatic three-dimensional architecture with carboxylic acid groups on the surface. The presence of sulfur pendants in the polymeric cavities demonstrated important role in the effective encapsulation of Bi-DOTA complexes ([Bi] = 5.
View Article and Find Full Text PDFEnterohemorrhagic Escherichia coli O157:H7 has been linked to both waterborne and foodborne illnesses, and remains a threat despite the food- and water-screening methods used currently. While conventional bacterial detection methods, such as polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays (ELISA) can specifically detect pathogenic contaminants, they require extensive sample preparation and lengthy waiting periods. In addition, these practices demand sophisticated laboratory instruments and settings, and must be executed by trained professionals.
View Article and Find Full Text PDFThe aim of this research is twofold: 1) to shed light on zika's binding and entry mechanism while 2) demonstrating the effectiveness of our magnetic relaxation platform to achieve this goal. Magnetic relaxation-sensitive nanoparticles (MRNPs) are used in a novel fashion to analyze binding interactions between the zika envelope protein (ZENV) and proposed host cell receptors: AXL, HSP70, and TIM-1. Computational analysis is also utilized to examine these binding interactions for the first time.
View Article and Find Full Text PDFHerein, we report the use of a theranostic nanocarrier (Folate-HBPE(CT20p)) to deliver a therapeutic peptide to prostate cancer tumors that express PSMA (folate hydrolase 1). The therapeutic peptide (CT20p) targets and inhibits the chaperonin-containing TCP-1 (CCT) protein-folding complex, is selectively cytotoxic to cancer cells, and is non-toxic to normal tissue. With the delivery of CT20p to prostate cancer cells via PSMA, a dual level of cancer specificity is achieved: (1) selective targeting to PSMA-expressing prostate tumors, and (2) specific cytotoxicity to cancer cells with minimal toxicity to normal cells.
View Article and Find Full Text PDFDespite advances in understanding the factors that cause many neurodegenerative diseases (NDs), no current therapies have yielded significant results. Cerium oxide nanoparticles (CeONPs) have recently emerged as therapeutics for the treatment of NDs due to their antioxidant properties. This report summarizes the recent findings regarding CeONPs in treatment of various NDs, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, ischemic stroke and amyotrophic lateral sclerosis.
View Article and Find Full Text PDFK-RAS driven non-small-cell lung cancer (NSCLC) represents a major cause of death among smokers. Recently, nanotechnology has introduced novel avenues for the diagnosis and personalized treatment options for cancer. Herein, we report a novel, multifunctional nanoceria platform loaded with a unique combination of two therapeutic drugs, doxorubicin (Doxo) and Hsp90 inhibitor ganetespib (GT), for the diagnosis and effective treatment of NSCLC.
View Article and Find Full Text PDFRapid detection and diagnosis of pathogenic strains of influenza is necessary for expedited treatment and quicker resolutions to the ever-rising flu pandemics. Considering this, we propose the development of novel magnetic relaxation nanosensors (MRnS) for the rapid detection of influenza through targeted binding with hemagglutinin. 2,6- and 2,3-sialic acid ligands and entry blocker peptides are conjugated to iron oxide nanoparticles to create functional MRnS.
View Article and Find Full Text PDFEnterohemorrhagic Escherichia coli O157:H7 presents a serious threat to human health and sanitation and is a leading cause in many food- and waterborne ailments. While conventional bacterial detection methods such as PCR, fluorescent immunoassays and ELISA exhibit high sensitivity and specificity, they are relatively laborious and require sophisticated instruments. In addition, these methods often demand extensive sample preparation and have lengthy readout times.
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