Shweta Dumoga

Bio: Shweta Dumoga is an academic researcher from Indian Institute of Technology Delhi. The author has contributed to research in topics: Camptothecin & Vesicle. The author has an hindex of 3, co-authored 3 publications receiving 33 citations.

Red Blood Cells-Derived Vesicles for Delivery of Lipophilic Drug Camptothecin.

Abstract: Recently, cell membrane-derived nanoparticles, particularly of RBCs, have been explored for delivery of hydrophilic solutes of varied size and complexities. So far, these naturally derived nanoparticles show a significant overlap with liposomes in terms of stability, solute encapsulation, and release. Unlike hydrophilic molecules, which are loaded inside the aqueous core, hydrophobic moieties largely partition inside the lipophilic shell, hence fate of these nanocarriers may be different. Since vesicles have more complex membrane architecture (due to natural lipids and additional proteins and glycoproteins), ease of loading hydrophobic drug, its release pattern, and overall particle stability cannot be compared to those of synthetic lipid-based carriers. Therefore, we derived nanovesicles (NVEs) from RBC membrane, loaded with hydrophobic drug camptothecin (CPT) and labeled noncovalently with amphiphilic fluorophore (CM-DiI). Although both CPT and CM-DiI are known to partition inside the membrane, the overall stability of NVEs and composition of membrane proteins, particularly CD47, "marker of self", did not change. Additionally, the developed NVEs were found to be nonphagocytic even in the presence of serum and showed minimal stimulation of macrophages to release cytokines. Further, this system showed slow release but strong retention of CPT and CM-DiI, respectively, over 24 h, hence appropriate for theranostic applications. Also, NVEs were internalized by lung carcinoma cells and possessed slightly higher toxicity than free CPT. When injected intravenously in balb/c mice, these nanovesicles showed higher retention in blood over 48 h and insignificant accumulation in vital organs like heart and kidneys, thus suggesting its potential for in vivo application. We believe that this system has superior stealth and comparable physicochemical properties to synthetic lipid-based nanocarriers; hence, it can be further developed as personalized medicine.

Modulating neutrophil extracellular traps for wound healing

Abstract: A diabetic microenvironment primes neutrophils for NETosis, a process of formation of neutrophil extracellular traps (NETs) that further degrades the neutrophils and makes them unavailable for the early-stage inflammatory processes. Mechanistically, simple modification of arginine residues of histones to citrulline by peptidylarginine deiminase (PAD4) enzyme is considered to be a prerequisite for NETosis. In fact, under diabetic conditions, an increase in PAD4-mediated NET formation is considered as one of the reasons for impaired wound healing. Therefore, in the present work, an alginate-GelMa (generally recognized as safe category by FDA, USA) based hydrogel scaffold containing a tripeptide (Thr-Asp-F-amidine) that inhibits PAD4 is developed, based on the hypothesis that inhibiting PAD4 enzyme might offer a way to enhance wound healing under diabetic conditions. The scaffolds are thoroughly characterized for their physicochemical and biological properties. Furthermore, neutrophil-scaffold interactions in terms of NETosis ability and release of other related biomarkers are studied. The wound healing ability is evaluated by a cell migration assay. In vivo wound healing efficacy of the developed scaffolds is demonstrated using a diabetic rat model. The results suggest a reduction in NETosis in the presence of a PAD4 inhibitor. Thus, the study demonstrates a novel scaffold system to deliver the PAD4 inhibitor that can be used to modulate NETosis and improve wound healing.

Immunology of Acute and Chronic Wound Healing

Abstract: Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.

Advances of hydrogel dressings in diabetic wounds.

Abstract: Currently, the treatment and care of diabetic wounds, which generally possess the characteristics of a high amputation rate, high recurrence rate and high mortality, has developed into a worldwide challenge. Wound dressings have been playing an important role in diabetic wound treatment and continuously innovated to obtain many amazing properties. Among them, hydrogel dressings have become one of the most attractive and promising wound dressings because of their considerable moisture retention, biocompatibility and therapeutic properties. In recent years, with the in depth understanding of the pathogenesis of diabetic wounds, various functionalized hydrogel dressings have been reported and shown encouraging results, which has brought great benefits to the improvement of diabetic wounds. In this work, we will systematically and comprehensively summarize the advances of hydrogel dressings in diabetic wounds, aiming to provide not only theoretical support for hydrogel dressing devising but also inspiration for diabetic wound treatment.

Extracellular Vesicles from Red Blood Cells and Their Evolving Roles in Health, Coagulopathy and Therapy

Abstract: Red blood cells (RBCs) release extracellular vesicles (EVs) including both endosome-derived exosomes and plasma-membrane-derived microvesicles (MVs). RBC-derived EVs (RBCEVs) are secreted during erythropoiesis, physiological cellular aging, disease conditions, and in response to environmental stressors. RBCEVs are enriched in various bioactive molecules that facilitate cell to cell communication and can act as markers of disease. RBCEVs contribute towards physiological adaptive responses to hypoxia as well as pathophysiological progression of diabetes and genetic non-malignant hematologic disease. Moreover, a considerable number of studies focus on the role of EVs from stored RBCs and have evaluated post transfusion consequences associated with their exposure. Interestingly, RBCEVs are important contributors toward coagulopathy in hematological disorders, thus representing a unique evolving area of study that can provide insights into molecular mechanisms that contribute toward dysregulated hemostasis associated with several disease conditions. Relevant work to this point provides a foundation on which to build further studies focused on unraveling the potential roles of RBCEVs in health and disease. In this review, we provide an analysis and summary of RBCEVs biogenesis, composition, and their biological function with a special emphasis on RBCEV pathophysiological contribution to coagulopathy. Further, we consider potential therapeutic applications of RBCEVs.