
Abhinav P AcharyaUniversity of Florida | UF
Abhinav P Acharya
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Introduction
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Publications
Publications (62)
Biomaterials can act as pro- or anti-inflammatory agents. However, effects of biomaterials crystallinity on immune responses are poorly understood. We demonstrate that the adjuvant-like behaviour of covalent organic framework (COF) biomaterial is dependent on its crystallinity. COF crystallinity is inversely correlated with the activation of mouse...
Intracortical microelectrodes (IMEs) are devices designed to be implanted into the cerebral cortex for various neuroscience and neuro-engineering applications. A critical feature of IMEs is their ability to detect neural activity from individual neurons. Currently, IMEs are limited by chronic failure, largely considered to be caused by the prolonge...
Rheumatoid arthritis (RA) causes inflammatory and metabolic imbalances in tissue, which then exacerbates inflammation in affected joints. Therefore, restoring tissue homeostasis is necessary for the remission of RA symptoms. In fact, the changes in immunological and metabolic tissue homeostasis at different stages of the disease is not well underst...
Evolving knowledge about the tumor–immune microenvironment (TIME) is driving innovation in designing novel therapies against hard‐to‐treat breast cancer. Targeting the immune components of TIME has emerged as a promising approach for cancer therapy. While recent immunotherapies aim at restoring antitumor immunity, counteracting tumor escape remains...
The immune response is a dynamic process by which the body determines whether an antigen is self or nonself. The state of this dynamic process is defined by the relative balance and population of inflammatory and regulatory actors which comprise this decision making process. The goal of immunotherapy as applied to, e.g. Rheumatoid Arthritis (RA), t...
Rheumatoid Arthritis (RA) is a chronic debilitating disease characterized by auto-immune reaction towards self-antigen such as collagen type II. In this study, we investigated the impact of exponentially decreasing levels of antigen exposure on pro-inflammatory T-cell responses in the collagen-induced arthritis (CIA) mouse model. Using a controlled...
Inhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 (inhibitor of PFKFB3, rate-limiting step in glycolysis), while simultaneously glycolysis and func...
Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of succinate in the TME modulates macrophage responses. Administering PES MPs locally with or without a...
Covalent organic framework (COF) crystalline biomaterials have great potential for drug delivery since they can load large amounts of small molecules (e.g. metabolites) and release them in a controlled manner, as compared to their amorphous counterparts. Herein, we screened different metabolites for their ability to modulate T cell responses in vit...
Alloy based implants have made a great impact in the clinic and in preclinical research. Immune responses are one of the major causes of failure of these implants in the clinic. Although the immune responses toward non-degradable alloy implants are well documented, there is a poor understanding of the immune responses against degradable alloy impla...
Boosting the metabolism of immune cells while restricting cancer cell metabolism is challenging. Herein, we report that using biomaterials for the controlled delivery of succinate metabolite to phagocytic immune cells activates them and modulates their metabolism in the presence of metabolic inhibitors. In young immunocompetent mice, polymeric micr...
Metabolic reprogramming of immune cells modulates their function and reduces the severity of autoimmune diseases. However, the long-term effects of the metabolically reprogrammed cells, specifically in the case of immune flare-ups, need to be examined. Herein, a re-induction rheumatoid arthritis (RA) mouse model was developed by injecting T-cells f...
Metabolites are not only involved in energy pathways but can also act as signaling molecules. Herein, we demonstrate that polyesters of alpha-ketoglutararte (paKG) can be generated by reacting aKG with aliphatic diols of different lengths, which release aKG in a sustained manner. paKG polymer-based microparticles generated via emulsion-evaporation...
Although different metabolic pathways have been associated with distinct macrophage phenotypes, the field of utilizing metabolites to modulate macrophage phenotype is in a nascent stage. In this report, we developed microparticles based on polymerization of alpha-ketoglutarate (a Krebs cycle metabolite), with or without encapsulation of spermine (a...
Activated effector T cells induce pro-inflammatory responses in rheumatoid arthritis (RA) which then lead to inflammation of the joints. In this report, we demonstrate that polymeric nanoparticles with alpha keto-glutarate (aKG) in their polymer backbone (termed as paKG NPs) modulate T cell responses in vitro and in vivo. Impressively, a low dose o...
The immune response is a dynamic process by which the body determines whether an antigen is self or nonself. The state of this dynamic process is defined by the relative balance and population of inflammatory and regulatory actors which comprise this decision making process. The goal of immunotherapy as applied to, e.g. Rheumatoid Arthritis (RA), t...
Drug delivery vehicles have made a great impact on cancer immunotherapies in clinics and pre-clinical research. Notably, the science of delivery of cancer vaccines and immunotherapeutics, modulating immune cell functions has inspired development of several successful companies and clinical products. Interestingly, these drug delivery modalities not...
An increasing number of findings highlight the fundamental role of metabolism in autoimmunity. This growing recognition of metabolic irregularities being a factor of immune dysregulation in autoimmunity has provided novel therapeutic opportunities. Although there have been advancements in the field of immunometabolism, it is important to note that...
The systemic pharmacotherapeutic efficacy of immunomodulatory drugs is heavily influenced by its route of administration. A few common routes for the systemic delivery of immunotherapeutics are intravenous, intraperitoneal, and intramuscular injections. However, the development of novel biomaterials, in adjunct to current progress in immunoengineer...
Dendritic cells (DCs) rely on glycolysis for their energy needs to induce pro-inflammatory antigen-specific immune responses. Therefore, inhibiting DC glycolysis, while presenting the self-antigen, may prevent pro-inflammatory antigen-specific immune responses. Previously we demonstrated that microparticles with alpha-ketoglutarate (aKG) in the pol...
Background
Pulmonary hypertension (PH) is a deadly disease characterized by vascular stiffness and altered cellular metabolism. Current treatments focus on vasodilation and not other root causes of pathogenesis. Previously, it was demonstrated that glutamine metabolism, as catalyzed by GLS1 (glutaminase 1) activity, is mechanoactivated by matrix st...
Adoptive Cell Transfer (ACT) therapies have recently fostered excitement for the treatment of hematogenous cancers. However, efficacy has largely been stunted in the treatment of solid tumors, especially for ovarian cancer, in part due to nutrient restriction within the tumor microenvironment. We recently demonstrated that intracellular delivery of...
Simple Summary
This review paper here describes the recent progress that has been made in chimeric antigen receptor (CAR) -based therapies for treatment of tumors and the role of metabolism in the tumor microenvironment in relation to these therapies. Moreover, this manuscript also discusses role of different CAR-based cells for treatment of solid...
Generating formulations for the delivery of a mixture of natural compounds extracted from natural sources is a challenge because of unknown active and inactive ingredients and possible interactions between them. As one example, natural cranberry extracts have been proposed for the prevention of biofilm formation on dental pellicle or teeth. However...
Vascularized composite allotransplantation (VCA) encompasses face and limb transplantation, but as with organ transplantation, it requires lifelong regimens of immunosuppressive drugs to prevent rejection. To achieve donor-specific immune tolerance and reduce the need for systemic immunosuppression, we developed a synthetic drug delivery system tha...
Polyurethane is an important biomaterial with wide applications in biomedical engineering. Here, we report a new method to make an azido-functionalized polyurethane pre-polymer with no need of post modification. This pre-polymer can easily form stable porous elastomers through click chemistry for crosslinking, instead of using a toxic polyisocyanat...
Significance
Vascularized composite allotransplantation (VCA) is an emerging field that is particularly beneficial for select amputees and patients with devastating soft tissue loss that is not amenable to conventional reconstructive surgeries. As with solid organ transplantation, VCA recipients are subjected to a lifelong regimen of antirejection...
Metal-organic frameworks (MOFs) formed from metals and organic ligands, are crystalline materials that are degradable in aqueous medium, and capable of releasing Ca and Sr ions. In this manuscript, the ability of MOFs to degrade and release osteogenic Ca and Sr ions was investigated. MOFs were generated by choosing osteoinductive Ca and Sr metals,...
Electronic cigarette (EC) use is gaining popularity as a substitute for conventional smoking due to the perception and evidence it represents a safer alternative. In contrast to the common perception amongst users that ECs represent no risk initial studies have revealed a complex composition of e-cigarette liquids. Conventional cigarette smoking is...
Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This infl...
The aqueous nature of complex coacervates provides a biologically-relevant context for various therapeutic applications. In this sense, biological applications demand a corresponding level of biocompatibility from the polyelectrolytes that participate in complex coacervation. Continued development with naturally-occuring polyelectrolytes such as he...
Although hematuria (blood in urine) is the most common symptom of bladder cancer, 70-98% of hematuria cases are benign. These hematuria patients unnecessarily undergo costly, invasive, and expensive evaluation for bladder cancer. Therefore, there remains a need for noninvasive office-based tests that can rapidly and reliably rule out bladder cancer...
Dry eye disease (DED) is a common ocular disorder affecting millions of individuals worldwide. The pathology of DED involves the infiltration of CD4⁺ lymphocytes, leading to tear film instability and destructive inflammation. In the healthy steady state, a population of immunosuppressive T-cells called regulatory T-cells (Treg) regulates proliferat...
As tumors employ complementary overlapping and/or independent mechanisms to evade immune surveillance, many emerging cancer immunotherapies attempt to target multiple pathways to eradicate malignant cells. Although modulation of independent pathways by simultaneous administration of multiple immune modulators (e.g., checkpoint inhibitors, cytokines...
Experimental vaccine adjuvants are being designed to target specific toll-like receptors (TLRs) alone or in combination, expressed by antigen presenting cells, notably dendritic cells (DCs). There is a need for high-content screening (HCS) platforms to explore how DC activation is affected by adjuvant combinations. Presented is a cell-based microar...
Divalent cations, the most prevalent minerals in the body, are responsible for a wide variety of cellular functions including signaling, proliferation, differentiation and cell death, and therefore their transmembrane transportation is tightly regulated. Despite the importance of divalent cations in cell activity, there are currently no intracellul...
Significance
Cancer research has relied on in vitro experiments with established cell lines to investigate the efficacy of chemotherapy drug panels, which limit clinical correlation. Targeting tumor-initiating cells could be a viable clinical strategy, but these cells are extremely rare, necessitating new methods for rapid and robust screening. We...
Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delive...
Stimuli-responsive polymers have a wide range of clinical applications from targeted drug delivery to medical diagnostics. On page 1433, D. Liepmann, N. Murthy, and co-workers develop a new stimuli-responsive polymer that is sensitive to reactive oxygen species, and utilize it to develop a point-of-care biosensor for measuring oxidative stress and...
A new turn-off fluorescent substrate for horseradish peroxidase is introduced, termed clics, which enhances the sensitivity of commercial enzyme-linked immunosorbant assays (ELISA) by 32-fold and detects chlamydial infections in patients. Clics are cost-effective, stable, and can be easily incorporated in commercial ELISA kits, and therefore should...
A digital point-of-care biosensor for measuring reactive oxygen species is presented based on novel reactive oxygen species responsive polymer-based electrodes. The biosensor is able to detect a drug-induced liver injury by monitoring the oxidative stress in the blood.
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Arteriovenous malformation (AVM) refers to a vascular anomaly where arteries and veins are directly connected through a complex, tangled web of abnormal AV fistulae without a normal capillary network. Hereditary hemorrhagic telangiectasia (HHT) types 1 and 2 arise from heterozygous mutations in endoglin (ENG) and activin receptor-like kinase 1 (ALK...
Acidosis causes millions of deaths each year and strategies for normalizing the blood pH in acidosis patients are greatly needed. The lactate dehydrogenase (LDH) pathway has great potential for treating acidosis due to its ability to convert protons and pyruvate into lactate and thereby raise blood pH, but has been challenging to develop into a the...
The low detection sensitivity of enzyme linked immunosorbent assays (ELISAs) is a central problem in science and limits progress in multiple areas of biology and medicine. In this report we demonstrate that the hydrocyanines, a family of fluorescent reactive oxygen species (ROS) probes, can act as turn on fluorescent horseradish peroxidase (HRP) pr...
The immune system is traditionally considered from the perspective of defending against bacterial or viral infections. However, foreign materials like implants can also illicit immune responses. These immune responses are mediated by a large number of molecular signals, including cytokines, antibodies and reactive radical species, and cell types, i...
In this report we present a new strategy for targeting chemotherapeutics to tumors, based on targeting extracellular DNA. A gemcitabine prodrug was synthesized, termed H-gemcitabine, which is composed of Hoechst conjugated to gemcitabine. H-gemcitabine has low toxicity because it is membrane impermeable, however it still has high tumor efficacy bec...
Magnesium has recently received an increased amount of interest due to its potential use in biodegradable implant applications. The rapid degradation of conventional Mg is, however, a major limitation that needs to be addressed in the design of these materials, along with consideration of toxicity in selection of alloying elements. In this study, f...
J. Neurochem. (2011) 118, 784–795.
Curcumin, a major active component of Curcuma longa, possesses antioxidant and neuroprotective activities. The present study explores the mechanisms underlying the neuroprotective effect of curcumin against corticosterone and its relation to 5-hydroxy tryptamine (5-HT) receptors. Exposure of cortical neurons to co...
A study was conducted to demonstrate that multilamellar lipid vesicles with crosslinked walls carrying protein antigens in the vesicle core and immunostimulatory drugs in the vesicle walls generated immune responses comparable to the strongest live vector vaccines. Investigations revealed that multilamellar lipid vesicles also entrapped immunostimu...
Stress is an unavoidable life experience. It induces mood, cognitive dysfunction and plasticity changes in chronically stressed individuals. Among the various brain regions that have been studied, the hippocampus and amygdala have been observed to have different roles in controlling the limbic-hypothalamic-pituitary-adrenal axis (limbic-HPA axis)....
It is known that adsorbed adhesive proteins on implanted biomaterials modulate inflammatory responses; however, modulation of dendritic cell (DC) responses upon interaction with adhesive proteins has only begun to be characterized. DCs are specialized antigen-presenting cells that modulate both innate and adaptive immune responses. Previously we ha...
Dendritic cells (DCs) are central regulators of the immune system that operate in both innate and adaptive branches of immunity. Activation of DC by numerous factors, such as danger signals, has been well established. However, modulation of DC functions through adhesion-based cues has only begun to be characterized. In this work, DCs were cultured...
Well-designed biomaterial polymer particle-based vaccines will optimally promote immune cell antigen-presenting behavior while minimizing adverse inflammatory responses to the particles and encapsulated drugs or adjuvants. It is important in the design of particle-based vaccines to consider possible harmful effects of immune response on tissue at t...
Immunogenomic approaches combined with advances in adjuvant immunology are guiding progress toward rational design of vaccines. Furthermore, drug delivery platforms (e.g., synthetic particles) are demonstrating promise for increasing vaccine efficacy. Currently there are scores of known antigenic epitopes and adjuvants, and numerous synthetic deliv...
Imaging of immune system and tissue response to immunogenic agents can be important to the development of new biomaterials. Additionally, quantitative functional imaging can be useful for testing and evaluation of methods to alter or control the immune system response to implanted materials. In this preliminary study, we employ spectral imaging and...
While it is well-known that adsorbed proteins on implanted biomaterials modulate inflammatory responses, modulation of dendritic cells (DCs) via adhesion-dependent signaling has only been begun to be characterized. In this work, we demonstrate that adhesive substrates elicit differential DC maturation and adaptive immune responses. We find that adh...