Kaushal Rege's research while affiliated with Arizona State University and other places

Publications (165)

Article
Surgical-site infections occur in 2-5% patients undergoing surgery in the US alone, impacting 300,000-500,000 lives each year, and presenting up to 11 times greater risk of death compared to patients...
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Background and Objective Chrysin and its derivatives proved to possess potential anti-tumour activity. Materials and Methods A new series of chrysin analogs containing 1,2,3-triazoles with different substituent groups (5a-5l) was designed, synthesized, and evaluated as potential anticancer agents. The synthesized compounds were characterized using...
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Poor strength, infection, leakage, long procedure times, and inflammation limit the efficacy of common tissue sealing devices in surgeries and trauma. Light‐activated sealing is attractive for tissue sealing and repair, and can be facilitated by the generation of local heat following absorption of nonionizing laser energy by chromophores. Here, the...
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Iron oxides are naturally occurring compounds, and several methods have been developed for generating iron oxide nanoparticles (IONPs) with a focus on precisely modulating their size and physicochemical properties. Facile synthesis approaches, narrow size distribution, ease of surface modification, tunable magnetic properties, and size-dependent el...
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Simultaneous delivery of small molecules and nucleic acids using a single vehicle can lead to novel combination treatments and multifunctional carriers for a variety of diseases. In this study, we report a novel library of aminoglycoside-derived lipopolymers nanoparticles (LPNs) for the simultaneous delivery of different molecular cargoes including...
Article
Synthetic materials that mimic the ability of natural occurring features to self‐actuate in response to different stimuli have wide applications in soft robotics, microdevices, drug delivery, regenerative medicine, and sensing. Here, unexpected and counter‐intuitive findings are presented in which a strongly polyelectrolytic hydrogel repels from st...
Article
Copper ions play an important role in several physiological processes, including angiogenesis, growth factor induction and extracellular matrix remodeling, that modulate wound healing and tissue repair. In this work, copper-loaded alginate fibers were generated and used as surgical sutures for repair of incisional wounds in live mice. Approximately...
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The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and effi...
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Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner may be able to modulate function of the immune cells . In this study, alpha-ketoglutarate (aKG) and diol based polymeric-microparticles (termed paKG MPs) were synthesized to provide sustained release of aKG and promote an immunosuppressive cellular ph...
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Radiation therapy is a common treatment modality employed in the treatment of cancer. High energy photons have been the primary source of radiation but when administered, leave an exit dose resulting in radiation damage to the adjacent healthy tissues. To overcome this, high energy electrons are employed in cases of skin cancer to minimize radiatio...
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A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal an...
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Despite the emergence of sophisticated technologies in treatment planning and administration, routine determination of delivered radiation doses remains a challenge due to limitations associated with conventional dosimeters. Here, we describe a gel-based nanosensor for the colorimetric detection and quantification of topographical radiation dose pr...
Article
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand that can preferentially induce apoptosis in cancer cells over normal cells. The transmembrane form of TRAIL has been shown to elicit much stronger activity than its soluble counterpart but delivery is a potential challenge. Here, we investigated the potential of amino...
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Numerous treatments have been developed to promote wound healing based on current understandings of the healing process. Hemorrhaging, clotting, and associated inflammation regulate early wound healing. We investigated treatment with a virus-derived immune modulating serine protease inhibitor (SERPIN), Serp-1, which inhibits thrombolytic proteases...
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The use of X-ray radiation in radiotherapy is a common treatment for many cancers. Despite several scientific advances, determination of radiation delivered to the patient remains a challenge due to the inherent limitations of existing dosimeters including fabrication and operation. Here, we describe a colorimetric nanosensor that exhibits unique c...
Article
Sutures are typically the primary means of soft tissue repair in surgery and trauma. Despite their widespread use, sutures do not result in immediate sealing of approximated tissues, which can result in bacterial infection and leakage. Nonabsorbable sutures and staples can be traumatic to tissue, and the trauma can be exacerbated by their subsequen...
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Quantitative approaches to structure-property relationships are critical for the accelerated design and discovery of biomaterials in biotechnology and medicine. However, the absence of definitive structures, unlike those available for small molecules or 3D crystal structures available for some proteins, has limited the development of Quantitative S...
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Under the heading "Methods-Synthesis of the Bioreducible Modified-PAE (mPAE)", on page 3, line 14-17, there is an error. The quantity unit of PAE and 2-iminothiolane hydrochloride needs to be corrected to mg instead of g.
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Purpose Lung cancer is one of the leading causes of deaths in the United States, but currently available therapies for lung cancer are associated with reduced efficacy and adverse side effects. Small interfering RNA (siRNA) can knock down the expression of specific genes and result in therapeutic efficacy in lung cancer. Recently, mTOR siRNA has be...
Chapter
Gene therapy has the potential to cure many different genetic diseases, if safe and effective gene delivery vectors can be developed. This chapter describes protocols for the synthesis of novel polymers using diglycidyl ether and diamine or polyamine monomers for transgene delivery and expression. The resulting poly (amino ethers) are able to trans...
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Inorganic nanomaterials have witnessed significant advances in areas of medicine including cancer therapy, imaging, and drug delivery, but their use in soft tissue repair and regeneration is in its infancy. Metallic, ceramic, and carbon allotrope nanoparticles have shown promise in facilitating tissue repair and regeneration. Inorganic nanomaterial...
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Effective transgene expression in mammalian cells relies on successful delivery, cytoplasmic trafficking, and nuclear translocation of the delivered vector, but delivery is impeded by several formidable physicochemical barriers on the surface of and within the target cell. Although methods to overcome cellular exclusion and endosomal entrapment hav...
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Nanoparticles have numerous uses in biomedical sciences, and this study addresses the mechanisms responsible for the formation of gold nanoparticles (GNPs) for measuring doses of ionizing radiation used in clinical radiotherapy. GNPs synthesized at various radiation doses were experimentally characterized and two mathematical models were developed...
Article
Organoids, which exhibit spontaneous organ specific organization, function, and multi-cellular complexity, are in essence the in vitro reproduction of specific in vivo organ systems. Recent work has demonstrated human pluripotent stem cells (hPSCs) as a viable regenerative cell source for tissue-specific organoid engineering. This is especially rel...
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Scaffolds generated from naturally occurring and synthetic polymers have been investigated in several applications because of their biocompatibility and tunable chemo‐mechanical properties. Existing methods for generation of 3D polymeric scaffolds typically cannot be parallelized, suffer from low throughputs, and do not allow for quick and easy rem...
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Proton beam therapy (PBT) is a state-of-the-art radiotherapy treatment approach that uses focused proton beams for tumor ablation.[1] A key advantage of this approach over conventional photon radiotherapy (XRT) is the unique dose deposition characteristics of protons, resulting in superior healthy tissue sparing. This results in fewer unwanted side...
Article
Plasmid DNA (pDNA) is an attractive therapeutic biomolecule in several diseases including cancer, AIDS, cystic fibrosis, Parkinson's disease and Alzheimer's disease. Increasing demand for plasmid DNA as a therapeutic biomolecule for transgene expression or vaccine applications necessitate novel approaches to bioprocessing. We previously described t...
Article
Objective: Laser tissue soldering using photothermal solders is a technology that facilitates rapid sealing using heat-induced changes in the tissue and the solder material. The solder material is made of gold nanorods embedded in a protein matrix patch that can be placed over the tissue rupture site and heated with a laser. Although laser tissue...
Article
Tumors undergo periods of dormancy followed by reactivation leading to metastatic disease. Arrest in the G0/G1 phase of the cell cycle and resistance to chemotherapeutic drugs are key hallmarks of dormant tumor cells. Here, we describe a 3D platform of bladder cancer cell dormancy and reactivation facilitated by a novel aminoglycoside-derived hydro...
Chapter
Laser tissue welding (LTW) is a sutureless technique for sealing incised or wounded tissue and is an attractive alternative or supplement in various surgeries. In LTW, chromophores convert laser light to heat which ultimately results in tissue sealing. While LTW has had success without exogenous absorbers, introducing chromophores that absorb near-...
Article
Radiotherapy is a highly complex and efficient treatment modality for ablation of malignant tumors. Despite several technological advances, determination of the dose delivered to the tumor remains a challenge due to limitations of complex fabrication, cumbersome operation, and high costs associated with current dosimeters. This study describes fund...
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Exosomes are nanoscale extracellular vesicles (EVs) that are shed from different cells in the body. Exosomes encapsulate several biomolecules including lipids, proteins, and nucleic acids, and can therefore play a key role in cellular communication. These vesicles can be isolated from different body fluids and their small sizes make them attractive...
Article
Electrochemical pseudo-capacitors are an attractive choice for energy storage applications because they offer higher energy densities than electrostatic or electric double layer capacitors. They also offer higher power densities in shorter durations of time, as compared to batteries. Recent efforts on pseudo-capacitors include biocompatible hydroge...
Article
Objective: Support Vector Regression (SVR) has become increasingly popular in cheminformatics modeling. As a result, SVR-based machine learning algorithms, including Fuzzy-SVR and Least Square-SVR (LS-SVR) have been developed and applied in various research areas. However, at present, few downloadable packages or public-domain software are availab...
Conference Paper
Radiotherapy has evolved into a highly complex and efficient treatment modality for ablation of malignant tumors. Treatments are typically administered in fractions of 2 Gy each (1 Gy = 1 Joule energy absorbed / kg), leading to a cumulative dose of 20-70 Gy depending on the disease. Despite several technological advances, determination of the dose...
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Targeted delivery of anticancer therapeutics can potentially overcome limitations of poor drug bioavailability, drug resistance, and off-target side-effects that are associated with current chemotherapeutic regimens. Folate receptors are overexpressed on several types of cancer cells including, ovarian, non-small cell lung, triple-negative breast a...
Article
The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic na...
Article
Ionizing radiation, which includes X-rays and gamma rays, is used in a variety of different applications, including in human health. However, high levels of exposure can result in significant morbidity and mortality in humans. Molecular and nanoscale systems that can detect different levels of ionizing radiation can ultimately lead to effective sen...
Article
Ever since the discovery of radioactivity, beneficial use of ionizing radiation has been pursued for the betterment of human health. In particular, fractionated radiotherapy is commonly used in the clinic for ablation of malignant tumors. Use of higher radiation dose fractions and complex dose trajectories necessitate measurements of radiation dose...
Article
Effective design of nanoparticle systems can have a significant impact on therapeutic delivery. Physicochemical factors including size, shape and surface chemistry of nanoparticles can play a significant role in determining the efficacy of drug and gene delivery to cells. Polymeric as well as inorganic nanoparticle systems have been investigated as...
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Eukaryotic cells maintain an immense amount of genetic information by tightly wrapping their DNA around positively charged histones. While this strategy allows human cells to maintain more than 25,000 genes, histone binding can also block gene expression. Consequently, cells express histone acetyl transferases (HATs) to acetylate histone lysines an...
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Modern radiation therapy is a complex process using highly automated linear accelerators that maximize dose to tumors and minimize incident dose to normal tissues. Dosimeters can help determine the radiation dose delivered to target diseased tissue while minimizing damage to surrounding healthy tissue. However, existing dosimeters can be complex to...
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Surgical site infection and postoperative leakage are complications that may develop following colorectal surgery and result in fatal consequences. Rapid, fluid-tight wound closure through laser tissue welding (LTW) can reduce postoperative leakage and thus decrease infection. Laser tissue welding involves generation of localized heat by exposing a...
Article
We describe the parallel synthesis of lipopolymers generated by conjugating alkanoyl chlorides to polymers derived from aminoglycoside antibiotic monomers as novel vehicles for transgene delivery and expression in mammalian cells. Parallel screening of lipopolymers led to the identification of six leads that demonstrated higher transgene expression...
Article
The objective of the present study was to synthesize and investigate the transgene expression efficacy of quaternized derivatives of aminoglycoside polymers in different cancer cell lines. A series of glycidyltrimethylammonium chloride (GTMAC) derivatives of aminoglycoside polymers (GTMAC-AM polymers), containing varying degrees of quaternization (...
Article
Effective vehicles are often required to deliver nucleic acids and drugs to diseased tissues due to poor stability, susceptibility to enzymatic degradation, and/or unfavorable pharmacokinetics associated with these therapeutic molecules. Nanostructures can be employed to load, target, and release nucleic acid and drug therapeutics selectively to pr...
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Human cells contain hundreds of kinase enzymes that regulate several cellular processes, which likely include transgene delivery and expression. We identified several kinases that influence gene delivery and / or expression by performing a kinome-level screen in which, we identified small-molecule kinase inhibitors that significantly enhanced non-v...
Conference Paper
The sophisticated vasculature of leaves has been replicated to aid in the construction of a microfluidic like device. Their abundance in nature necessitates research into their development into low-cost, renewable platforms for various applications. The presence of functional groups of amines, hydroxyls in the leaf vasculature along with its porous...
Conference Paper
Abstracts: * Identification of Kinase Inhibitors for Enhanced Polymer-Mediated Transgene Expression.docx (13.9KB) - Uploading Abstracts
Conference Paper
Widespread use of ionizing radiation, including X-rays and gamma rays, in food technology, imaging and cancer therapy necessitates precise control over dose, which in turn motivates the development of sensors that can detect various energy levels. A variety of dosimeters, including one-dimensional ion-chambers have been explored for different appli...
Conference Paper
Abstracts: * Modulation of Cellular Behavior by Inhibition of Intracellular Enzymes to Enhance... Poster Abstract 2014.docx (15.3KB) - Uploading Abstracts
Conference Paper
Plasmid DNA is playing a decisive role as a therapeutic option for multiple diseases such as cancer, cystic fibrosis and as DNA vaccines. Future clinical treatments that use plasmid DNA must be able to produce pharmaceutical grade quality of DNA in large amounts. Currently, plasmid DNA is grown in bacterial broths from which is extracted by cell ly...
Conference Paper
Abstracts: * Identification of Kinase Inhibitors for Enhanced Polymer-Mediated Transgene Expression_Award Submission.docx (13.9KB) - Uploading Abstracts
Conference Paper
Abstracts: * HDAC Inhibition Enhances Transgene Expression Abstract_AIChE 2014 Atlanta.docx (14.5KB) - Uploading Abstracts
Article
Leaves are an abundant natural resource, and consist of a sophisticated microfluidic network of veins that transports nutrients and water, thereby enabling photosynthesis. Here, we simultaneously exploit the microfluidics as well as chemistry of processed leaf vasculature (venation) in order to template the in situ generation of plasmonic metal (go...
Article
Plasmid DNA (pDNA) therapeutics are under investigation for gene therapy and DNA vaccines against diseases including cancer, cystic fibrosis and AIDS. In addition, several applications in modern biotechnology require pDNA for transient protein production. Here, we describe the synthesis, characterization, and evaluation of microbeads ('Amikabeads')...
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Plasmonic nanoparticles have been increasingly investigated for numerous applications in medicine, sensing, and catalysis. In particular, gold nanoparticles have been investigated for separations, sensing, drug / nucleic acid delivery, and bioimaging. In addition, silver nanoparticles demonstrate antibacterial activity resulting in potential applic...
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Nanomaterials have the potential to solve some of the toughest challenges facing modern medicine. Their unique optical, magnetic and chemical properties at the nanoscale make them different from their macroscale counterparts. Successful application of nanomaterials can revolutionize therapeutics, diagnostics and imaging in several biomedical applic...
Article
Gene therapy has garnered significant attention as a therapeutic approach for bladder cancer but efficient delivery and gene expression remain major hurdles. The goal of this study was to determine if cationic polymers can enhance adenoviral gene expression in cells that are difficult to transduce in vitro and to subsequently investigate lead candi...
Article
We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in hi...
Conference Paper
Ionizing radiation, including gamma rays and X-rays, has numerous applications in nuclear energy, astrophysics, food technology1, biomedical imaging2, and cancer therapy3 However, ionizing radiation causes DNA damage in cells5 leading to carcinogenesis, and can also cause deleterious effects on the environment6. Consequently, the necessity for dete...
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Full-text available
TNFα-related apoptosis-inducing ligand (TRAIL) induces death selectively in cancer cells. However, subpopulations of cancer cells are either resistant to or can develop resistance to TRAIL-induced death. As a result, strategies that overcome this resistance are currently under investigation. We have recently identified several US FDA-approved drugs...
Conference Paper
Cationic polymers are attractive candidates for transgene delivery and expression since they are considered to be safer alternatives to viral delivery vehicles. Amphiphilic polymers that combine cationic character with hydrophobicity are hypothesized to possess high efficacies for nucleic acid condensation and uptake across cellular membranes. Here...
Conference Paper
Despite their popularity, two dimensional cell cultures fail to capture the inherent complexity within a 3D tumor. Three dimensional co-culture systems are effective in vitro models of the tumor microenvironment, since they can better represent cell-cell contacts and interactions, existence of metabolic and nutrient gradients, necrotic core regions...