Department of Biomedical Engineering

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IIT Hyderabad

We consider a two-dimensional (2-D) model of an autophoretic particle. Beyond a certain emission/absorption rate (characterized by a dimensionless Péclet number,) the particle is known to undergo a bifurcation from a non-motile to a motile state, with different trajectories, going from a straight to a chaotic motion by increasing. From the full model, we derive a reduced closed model which involves only two time-dependent complex amplitudes and corresponding to the first two Fourier modes of the solute concentration field. It consists of two coupled nonlinear ordinary differential equations for and and presents several advantages: (i) the straight and circular motions can be handled fully analytically; (ii) complex motions such as chaos can be analysed numerically very efficiently in comparison with the numerically expensive full model involving partial differential equations; (iii) the reduced model has a universal form dictated only by symmetries (meaning that the form of the equations does not depend on a given phoretic model); (iv) the model can be extended to higher Fourier modes. The derivation method is exemplified for a 2-D model, for simplicity, but can easily be extended to three dimensions, not only for the presently selected phoretic model, but also for any model in which chemical activity triggers locomotion. A typical example can be found, for example, in the field of cell motility involving acto-myosin kinetics. This strategy offers an interesting way to cope with swimmers on the basis of ordinary differential equations, allowing for analytical tractability and efficient numerical treatment. © 2022 The Author(s). Published by Cambridge University Press.

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Fulltext

Journal of Fluid Mechanics

A reduced model for a phoretic swimmer

Nano-biofertilizers are the biologically synthesized nano-fertilizers from the microbes and plants employed in the agricultural fields to promote crop production and protection. For instance, specifically, the plant growth-promoting microbes (PGPM) having significant growth promotion and antagonistic traits, have led to their wide range of applications as nano-biofertilizers. In the agricultural scenario, the soil, crops, microbiome and nano-biofertilizers often influence one another and their ecological systems. The application of these PGPM nano-biofertilizers often promised enhanced soil quality and crop protection during both abiotic and biotic stress conditions through their bioactive compounds. This made the PGPM nano-biofertilizers as key players of yield enhancers and an advantage to the ever-increasing global food demand. However, day by day, nanotechnology being more beneficial and economical, many researchers and agriculturalists are shifting towards their wide range of applications in modern agricultural practices. This challenges the nanoparticles (NPs) dosage, toxicity, and their environmental footprint in the agricultural soils over a long time. This chapter highlights the key features of the PGPM nano-biofertlizers, their type and time of application, their dynamics on plant soil health, and the necessity for better and safer marketing applications of these NPs in the agricultural fields. © 2022, Indian National Science Academy.

Proceedings of the Indian National Science Academy

Nano-biofertilizers on soil health, chemistry, and microbial community: benefits and risks

Exosomes play pivotal roles in intercellular communication, and pathophysiological functions. In this study, we aimed to understand the role of exosomal proteome derived from C. albicans infected mice (C57BL/6) eyeball. Exosomes were characterized by Dynamic Light Scattering and Western blot, quantified and subjected to LC-MS/MS and cytokine quantification by ELISA. The average size of exosomes was 170–200 nm with number of exosomes amounted to 1.42 × 1010 in infected set compared to control (1.24 × 109). Western blot was positive for CD9, CD63 and CD81 confirming the presence of exosomes. IL-6, IL1β, TNF-α, and IFN-γ levels were significantly elevated in infected eye at 72 h.p.i. Proteomic analysis identified 42 differentially expressed proteins, of these 37 were upregulated and 5 were downregulated. Gene Ontology (GO) revealed enrichment of cell adhesion, cytoskeleton organisation, and cellular response proteins such as aquaporin-5, gasdermin-A, CD5 antigen-like, Catenin, V-ATPase, and vesicle associated protein. Additionally, KEGG pathway analysis indicated the association of metabolic and carbon signalling pathways with exosomes from C. albicans infected eye. The protein cargo in exosomes released during endophthalmitis with C. albicans seems to play a unique role in the pathogenesis of the disease and further validations with larger cohort of patients is required to confirm them as biomarkers. © 2022 Elsevier Inc.

Experimental Cell Research

Proteomic profiling of exosomes in a mouse model of Candida albicans endophthalmitis

Exploring the enhanced permeability and retention (EPR) effect through therapeutic nanoparticles has been a subject of considerable interest in tumor biology. This passive targeting based phenomenon exploits the leaky blood vasculature and the defective lymphatic drainage system of the heterogeneous tumor microenvironment resulting in enhanced preferential accumulation of the nanoparticles within the tumor tissues. This article reviews the fundamental studies to assess how the EPR effect plays an essential role in passive targeting. Further, it summarizes various therapeutic modalities of nanoformulation including chemo-photodynamic therapy, intravascular drug release, and photothermal immunotherapy to combat cancer using enhanced EPR effect in neoplasia region. © 2022 Elsevier B.V.

Photodiagnosis and Photodynamic Therapy

Enhanced permeability and retention effect: A key facilitator for solid tumor targeting by nanoparticles

This study reports a hybrid lipo-polymeric nanosystem (PDPC NPs) synthesized by a modified hydrogel-isolation technique. The ability of the nanosystem to encapsulate hydrophilic and hydrophobic molecules has been demonstrated, and their enhanced cellular uptake has been observed in vitro. The PDPC NPs, surface coated with gold by in situ reduction of chloroauric acid (PDPC-Au NPs), showed a photothermal transduction efficacy of ∼65%. The PDPC-Au NPs demonstrated an increase in intracellular ROS, triggered DNA damage and resulted in apoptotic cell death when tested against breast cancer cells (MCF-7). The disintegration of PDPC-Au NPs into smaller nanoparticles with near-infrared (NIR) laser irradiation was understood using transmission electron microscopy imaging. The lipo-polymeric hybrid nanosystem exhibited plasmon-enhanced fluorescence when loaded with IR780 (a NIR dye), followed by surface coating with gold (PDPC-IR-Au NPs). This paper is one of the first reports on the plasmon-enhanced fluorescence within a nanosystem by simple surface coating of Au, to the best of our knowledge. This plasmon-enhanced fluorescence was unique to the lipo-polymeric hybrid system, as the same was not observed with a liposomal nanosystem. The plasmon-enhanced fluorescence of PDPC-IR-Au NPs, when applied for imaging cancer cells and zebrafish embryos, showed a strong fluorescence signal at minimal concentrations of the dye. The PDPC-IR-Au NPs were also applied for photothermal therapy of breast cancer in vitro and in vivo, and the results depicted significant therapeutic benefits. © 2022 The Royal Society of Chemistry.

Nanoscale

A plasmon-enhanced fluorescent gold coated novel lipo-polymeric hybrid nanosystem: synthesis, characterization and application for imaging and photothermal therapy of breast cancer

Chemo-photothermal therapy is one of the emerging therapies for treating triple-negative breast cancer. In this study, we have used ionotropic gelation method to fabricate chitosan and IR806 dye-based polyelectrolyte complex (CIR-PEx) nanoparticles. These nano-complexes were in size range of 125 ± 20 nm. The complexation of IR 806 dye with chitosan improved photostability, photothermal transduction, and showed excellent biocompatibility. Cancer cells treated with CIR-PEx NPs enhanced intracellular uptake within 5 h of incubation and also displayed mitochondrial localization. With the combination of CIR-PEx NPs and a chemotherapeutic agent (i.e., mitoxantrone, MTX), a significant decline in cancer cell viability was observed in both 2D and 3D cell culture models. The chemo-photothermal effect of CIR-PEx NPs + MTX augmented apoptosis in cancer cells when irradiated with NIR light. Furthermore, when tested in the 4 T1-tumor model, the chemo-photothermal therapy showed a drastic decline in tumor volume and inhibited metastatic lung nodules. The localized hyperthermia caused by photothermal therapy reduced the primary tumor burden, and the chemotherapeutic activity of mitoxantrone further complemented by inhibiting the spread of cancer cells. The proposed chemo-photothermal therapy combination could be a promising strategy for treating triple-negative metastatic breast cancer. © 2022 Elsevier B.V.

International Journal of Biological Macromolecules

Chitosan IR806 dye-based polyelectrolyte complex nanoparticles with mitoxantrone combination for effective chemo-photothermal therapy of metastatic triple-negative breast cancer

Personalized medicine has gained much attention as a major milestone in cancer treatment to overcome the underlying genetic variations in an individual's response to drug. Nanotheranostics have become a potential tool to overcome the critical challenges faced in personalized medicine development. In this perspective, iron oxide nanoparticles represent a potential class of nanomaterials attributing to their unique physicochemical properties for theranostic applications. This review summarizes the recent advances in the use of iron oxide nanoparticles (IONPs) in various applications such as magnetic resonance imaging (MRI), magnetically activated cell sorting, magnetic biosensors, magnetic hyperthermia, drug delivery, radioimmunotherapy, magnetofection and ferrotherapy in detail. © 2022 Elsevier B.V.

Department of Physics

Journal of Drug Delivery Science and Technology

Iron oxide nanoparticles for theranostic applications - Recent advances

Herbal biomolecules (HBs) are plant components with discrete biological activities and therapeutic potentials. Historically these molecules were used in traditional medicinal systems for the treatment of various ailments. Ongoing research on ethnobotanical use of these HBs provide a scientific rationale for their use as potential nutraceuticals. This chapter reviews such plant-based bioactive molecules that can be used as food supplements and nutraceuticals. “Nutraceuticals” is a broad term that sums up all the food products with general health to prevent and treat any disease conditions. These products have generated great demand all over the world. The global market of nutraceuticals is estimated to be 198.7 billion USD in 2016, increasing with a 7.5% compound annual growth rate. This chapter also focuses on a diverse range of plant-based bioactive nutraceuticals based on their food sources, their pharmacological activities, and chemicals. Upon further development, these materials can yield efficient nutraceuticals agents that can contribute to society’s better health. © 2022 Elsevier Inc. All rights reserved.

Herbal Biomolecules in Healthcare Applications

Herbal biomolecules as nutraceuticals

One of the key factors required in tissue engineering/regeneration is to create a dynamic platform to increase the interaction of cells in response to various stimuli. In this context, facile synthesis of modified polyethylene glycol (FL PEG) encapsulated Iron Oxide nanoparticles [PoeM (Fe) NPs] is reported for its wound healing application in presence of an external magnetic field. Iron Oxide nanoparticles (8 ± 2nm) are synthesized and coated with FL PEG resulting in the formation of PoeM (Fe) NPs. The synthesized nanoparticles are characterized for their UV-Vis absorbance, DLS and TEM. These PoeM (Fe) NPs show excellent biocompatibility and enhanced wound healing activity in L929 fibroblasts when compared with control groups. This study could pave the way for the development of novel biomimetic nanosystems for wound healing applications. © 2002-2012 IEEE.

IEEE Transactions on Nanotechnology

Modified Polyethylene Glycol Encapsulated Iron Oxide Nanoparticles for Accelerated Wound Healing Application

Activated microglia helps in resolving injury and supports wound healing. However, prolonged activation of microglia can lead to the aggravation of wound. Objective: The present study investigates neuronal injury-induced inflammatory response in microglia and how it is influenced by the treatment with an anti-inflammatory formulation, Eugenol encapsulated liposomes. Method: We introduced injury in an in vitro model of neuronal and microglia origin cell lines using scratch assay and evaluated wound closure rates with respect to treatment. On similar lines, both cell lines were treated in a combinatorial model using Eugenol encapsulated liposomes and investigated the effect of secreted factors in Conditioned Media (CM) on Reactive Oxygen Species (ROS) production, cell viability etc. We also evaluated the polarization properties of microglia in case of an injury by evaluating the amount of nitrite release. Further, in a co-culture model, we introduced neuronal injury in the vicinity of microglia. We then evaluated the inflammatory response of microglia after incubating the injured cells with the formulation for an hour. Results: Individual wounds, CM and co-culture models of neuronal injury treated with Eugenol encapsulated liposomes indicated a decrease in the production of ROS and pro-inflammatory microglia, with the latter displaying an enhanced difference (50–75% with respect to control). The markers produced by microglia cells with respect to an inflammatory condition followed by treatment with Eugenol encapsulated liposomes were investigated using ELISA and Western blotting. There was a reduction in the amount of pro-inflammatory markers TNF-α, IL-1β and an increase in the amount of anti-inflammatory markers IL-10 and IL-4. In control and treatment groups, cardiac rhythm was found to be in the basal levels (100–150 beats per minute). Viability of the embryos were also unaffected due to the treatment in individual group of 20 embryos each. Further, uptake of the formulation in embryos 2,3 & 4 days post fertilization (dpf) were analyzed. Co-encapsulating tracker dye, Nile red within the formulation indicated encapsulated tracker dye crossing organ barriers with respect to free dye. Conclusion: Neuronal injury causes microglial activation. Prolonged microglial activation hinders wound closure and can lead to secondary trauma. The present study was conducted using an in vitro scratch assay wound model. Treating the site of injury with an anti-inflammatory formulation, Eugenol loaded liposomes, converts pro-inflammatory microglia to an anti-inflammatory state and increases the rate of wound closure. © 2022