Biology subjects

Bhatia, D. D.

Publications and source records attributed to Bhatia, D. D..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Synthesis of Metal-Organic Framework (MOF) Based Composites for pH-Responsive Drug Delivery

Metal-Organic Frameworks (MOFs) are nanoporous, and nanostructured resources crafted from hydrocarbon-based linkers connecting inorganic metal nodes. A considerable amount of curcumin can be encapsulated within MOFs porous structure, shielding it from deterioration. The curcumins solubility was significantly improved by including carbon quantum dots (QDs) into the nanocomposite. In this study, curcumin was encapsulated using the double emulsion approach using MOF-based nanoparticles and pH-sensitive chitosan/PEG hydrogel. The nanocarrier was characterised by X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FE-SEM), Dynamic light scattering (DLS), and zeta potential. UV spectroscopy and spectrofluorimetric provided insights into the binding of curcumin to the added QDs. Curcumin loading and encapsulation efficiency were found to be about 31% and 85%, respectively. The release profile of curcumin showed pH-dependence and controlled release by the nanocomposite, following the K-P diffusion model. Biocompatibility against the MCF-7 breast cancer cells validated the anti-cancer potential of the nanocarrier.

bioengineering↗

bioRxiv2025

In silico self-assembly and complexation dynamics of cationic lipids with DNA nanocages to enhance lipofection

DNA nanostructures are promising materials for drug delivery due to their unique topology, shape, size control, biocompatibility, structural stability and blood-brain-barrier (BBB) penetration capability. However, their cellular permeability is hindered by strong electrostatic repulsion from negatively charged cellular membranes, posing a significant obstacle to the use of DNA nanostructures as a drug delivery vehicle. Recent experimental studies have shown enhanced cellular uptake for the conjugate binary mixtures of DNA Tetrahedron (TDN) with cationic lipid N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) compared to TDN alone. However, the cationic DOTMA lipids binding mechanism with the TDN nucleotides is still elusive. Using fully atomistic MD simulations, we aim to understand the molecular interactions that drive the formation and stability of the TDN-DOTMA binary complexes in a physiological environment. Our results uncovered that lipid concentration plays a crucial role in the energetics of the TDN-DOTMA association. We also report that distinct timescales are associated with the self-assembly of cationic DOTMA lipids first, followed by the complexation of self-assembled DOTMA lipid clusters with the TDN nucleotides, where electrostatics, hydrophobicity, and hydrogen bonding are the key interactions that drive the formation and stability of these complexes. These results provide molecular insights into TDN-DOTMA interactions, highlighting the lipid self-assembly dynamics, complex stability, and morphology, paving the way for the better rational design of cationic lipid functionalized DNA nanostructures for efficient drug delivery and transfection.

biophysics↗

bioRxiv2025

Engineered Fluorescent Carbon Dots for Selective Cellular Bioeffects: A Comparative Study of Cancer and epithelial Cells

Cancer remains one of the most critical global health challenges, with early detection being essential for effective treatment and improved survival rates. However, conventional diagnostic tools often fail to detect cancer at early stages due to limitations such as low sensitivity, high cost, and dependence on large tumour presence. Commercial dyes used for imaging are frequently hindered by poor water solubility, toxicity, instability, and high expense. In recent years, CDs have emerged as promising fluorescent probes due to their nanoscale size, tenable surface properties, strong fluorescence, and excellent biocompatibility. make them applicable to various biological applications such as bioimaging, drug delivery, and tissue engineering. In this study, CDs were synthesized using citric acid and ascorbic acid as carbon sources via a reflux method at 130 {degrees}C for 12 hours in a water-ethanol medium. The resulting CDs exhibited high water solubility, strong photostability, and low toxicity. Notably, they effectively distinguished cancerous cells from normal cells. And showing higher uptake in cancer cells due to increased membrane permeability and metabolic activity. Higher uptake means more accumulation within cells that leads to an increment in fluorescence intensity, based on the fluorescent intensity distinguishing the cancer cells and normal cells. These findings highlight the potential of CDs as cost-effective, biocompatible imaging agents for cancer diagnosis and cellular studies.

bioengineering↗

bioRxiv2025

Alpha-tocopherol conjugated DNA tetrahedron with enhanced cellular uptake and selective cytotoxicity for cancer therapeutics

One of the most fatal diseases in the world, cancer, lacks proper therapies that are toxic to cancer cells and specifically kill them. A newly emerging field, DNA nanotechnology facilitates the design of programmable, biocompatible DNA-based nanostructures, with applications spanning drug delivery, biosensing, and a number of applications in biomedical and therapeutics. However, the negatively charged outer leaflet of the plasma membrane poses challenges for the uptake of negatively charged DNA nanostructures. Strategies such as functionalizing DNA nanostructures with cationic lipids have been attempted, but these approaches have yielded conflicting results and certain limitations including stability and ambiguity of lipid functionalisation. Additionally, drug delivery using DNA tetrahedron (TD) and other conventional therapies has shown off-target effects due to the non-specificity of the drug. To address these challenges, this study utilizes a hydrophobic molecule, alpha-tocopherol succinate (AT), known for its selective cytotoxicity towards malignant cells over normal cells at appropriate concentrations. Covalently conjugating AT with TD preserved its selective toxicity property and enhance the cellular internalisation of DNA tetrahedron in specific cell lines. ROS generation was increased and led to apoptosis in malignant cell lines specifically. This suggests the development of a novel system with specific cytotoxicity towards cancer cells with increased uptake.

bioengineering↗

bioRxiv2025

Synthesis and In Vitro Assessment of Triazole-Based Compounds as Potential Inhibitors of Herpes Simplex Virus Type 1

A library of novel 1,2,4-triazole derivatives fused with a pyrazine moiety (5a-5t) was successfully synthesized and evaluated for their therapeutic potential against HSV-I virus and oxidative stress. These compounds were assessed for anti-inflammatory, antioxidant, and anti-HSV activities, demonstrating encouraging biological profiles. In particular, compounds 5f and 5t exhibited markedly improved antiviral efficacy compared to the reference drug, Acyclovir. The antioxidant capacity was also notable, with compound 5b showing exceptional radical scavenging potential. To better understand the interaction at the molecular level, docking studies were conducted, indicating that these molecules could potentially inhibit HSV1, a key enzyme required for viral replication. Also, in silico testing was conducted for assessing drug-likeness, ADME characteristics, and stability of metabolism which was helpful for optimizing further lead designs. Although the experimental methods were accurately implemented, some human error such as timing during administration of the compounds, measuring, and other tasks may have slight variations which are not entirely avoidable. These possible blunders are, however, unlikely to change significantly the observed trends. Ultimately, the study emphasizes these new hybrids of triazole-pyrazine as potential precursors for the synthesis of powerful anti-HSV-I and possibly antibacterial medicines, which require more advanced pharmacological and clinical research.

biochemistry↗

bioRxiv2025

Competence of DNA Tetrahedron and Exosomes as Nanocarriers for Epirubicin drug delivery in Breast Cancer Cells

Epirubicin, a chemotherapeutic agent, is used in treatment of metastatic breast cancer treatment. However, poor intracellular delivery and systemic toxicity are its major limitations. Our study evaluates the use of DNA tetrahedron (TD) structures and exosomes for targeted delivery of epirubicin to enhance its therapeutic efficacy. Increased intracellular concentration of epirubicin was observed in Flow cytometer when delivered via the TD: Epi system compared to free epirubicin. Cell viability assays using Annexin V-FITC and propidium iodide staining revealed higher apoptosis rates in the TD: Epi system. Exosomes, primarily 100 {+/-} 20 nm in size (99% of particles), exhibit a - 28.5 mV zeta potential, ensuring colloidal stability. SEM and TEM confirm their spherical shape, uniform size, and double membrane structure. The TD: Epi system showed the highest efficacy in RT-qPCR analysis, followed by Epirubicin + Exosomes systems and epirubicin alone, further corroborated with western blot results. While exosomes also provided improved delivery and therapeutic outcomes compared to free epirubicin, they were less effective than the TD: Epi system. These results suggest that the TD carrier significantly enhances the delivery and apoptotic efficacy of epirubicin when compared to exosome-based delivery or epirubicin alone offering a promising strategy for improving treatment outcomes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=178 HEIGHT=200 SRC="FIGDIR/small/637654v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@10e0393org.highwire.dtl.DTLVardef@10ce3eeorg.highwire.dtl.DTLVardef@148552aorg.highwire.dtl.DTLVardef@1cf4664_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Neurotransmitter loaded DNA nanocages as potential therapeutics for α-synuclein based neuropathies in cells and in vivo

Parkinsons disease is one of the neuropathies characterized by accumulation of -synuclein protein, leading to motor dysfunction. Levodopa is the gold standard treatment, however, in long term usage, it leads to levodopa induced dyskinesia (LID). New therapeutic options are need of the hour to treat the -synuclein based neuropathies. The role of imbalance of neurotransmitters other than dopamine has been underestimated in -synuclein based neuropathies. Here, we explore the role of serotonin, epinephrine and norepinephrine as a therapeutic moiety. For the efficient in vivo delivery, we use DNA nanotechnology-based DNA tetrahedra that has shown the potential to cross the biological barriers. In this study, we explore the use of DNA nanodevices, particularly DNA tetrahedron functionalized with neurotransmitters, as a novel therapeutic approach for MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced Parkinsons disease in PC12 cellular system. We first establish the effect of these nanodevices on clearance of -synuclein protein in cells. We follow the study by understanding the various cellular processes like ROS, iron accumulation and lipid peroxidation. We also explore the effect of the neurotransmitter loaded nanodevices in in vivo zebrafish model. We show that neurotransmitter loaded DNA nanocages can potentially clear the MPTP induced -synuclein aggregates in cells and in vivo. The findings of these work open up new avenues for use of DNA nanotechnology by functionalizing it with neurotransmitters for future therapeutics in treatment of neurodegenerative diseases such as Parkinsons disease. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/626934v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@94c347org.highwire.dtl.DTLVardef@a08756org.highwire.dtl.DTLVardef@1153704org.highwire.dtl.DTLVardef@1cefebb_HPS_FORMAT_FIGEXP M_FIG C_FIG TD:NT can clear -synuclein by targeting the ferroptosis pathway.

bioengineering↗

bioRxiv2024

Peptide modified, programmable DNA tetrahedra to modulate autophagy in biological systems

Autophagy is a critical cellular pathway for degrading and recycling damaged components, essential for maintaining cellular homeostasis. Dysregulation of autophagy contributes to various diseases, including neurodegenerative disorders, cancers, and metabolic syndromes, highlighting the therapeutic potential of controlled autophagy induction. However, current autophagy inducers often lack specificity and may inadvertently trigger apoptosis, limiting their clinical utility. Here, we present a DNA tetrahedron-BH3 peptide nanosystem (Tdpep) engineered to selectively induce autophagy by disrupting the Beclin 1-Bcl2 interaction, a pivotal regulatory point in autophagy initiation. Tdpep, functionalized with a BH3 peptide targeting Bcl2, demonstrated efficient cellular uptake and minimal cytotoxicity in HeLa cells at concentrations up to 200nM. Autophagy induction was confirmed by increased LC3B puncta formation and fluorescence intensity comparable to that induced by rapamycin. Autophagy flux analysis of Tdpep with bafilomycin A1 validated enhanced autophagic activity rather than flux inhibition. Furthermore, Tdpep treatment significantly reduced cellular ROS levels, indicating effective autophagic turnover. Apoptosis assays showed that Tdpep did not induce apoptosis, confirming its selective autophagy induction. Furthermore, Tdpep nanosystem also induced autophagy in Danio rerio larvae in vivo model. Thus, this targeted DNA tetrahedron nanosystem provides a precise autophagy modulation platform with minimized off-target effects, offering a promising therapeutic strategy for diseases associated with autophagy dysfunction. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/621781v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@193cde5org.highwire.dtl.DTLVardef@b2a041org.highwire.dtl.DTLVardef@13711eaorg.highwire.dtl.DTLVardef@792bb5_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Pathophysiological Implications of Nucleotide Self-Assembly: Adenine-Derived Nucleotides Aggregation in Disease Mechanisms

Adenine nucleotides, including adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate, play pivotal roles in cellular bioenergetics, nucleic acid metabolism, and signal transduction. However, their propensity to undergo self-assembly and form supramolecular aggregates under certain conditions is not well-characterized. In this study, we examined the self-assembly, aggregation, and cytotoxicity of AMP, ADP, and ATP in both fresh and aged conditions. Utilizing advanced microscopy techniques, Thioflavin T (ThT) fluorescence assays, and cross-seeding experiments, we identified oligomer formation in freshly prepared nucleotide solutions, which progressed to larger, more stable aggregates over time. The cytotoxic potential of these nucleotide aggregates was assessed using in vitro models, including human retinal pigment epithelial (RPE-1) and colorectal carcinoma (HCT-116) cell lines. Our findings demonstrate that nucleotide aggregation induces significant cytotoxic effects, particularly in aged conditions. Further investigations into bacterial toxicity models revealed similar deleterious impacts, indicating a broad-spectrum biological stress response to nucleotide aggregates. These results suggest that nucleotide self-assembly and aggregation may contribute to cellular dysfunction, offering new insights into their non-canonical roles in disease pathophysiology, potentially analogous to protein misfolding disorders.

bioengineering↗

bioRxiv2024

Assembly of branched chain amino acid (BCAA) to toxic fibrils may be related to pathogenesis of Maple syrup urine disease (MSUD)

Inborn errors of metabolism (IEMs) are a group of diseases caused by mutations in single genes, leading to the buildup of metabolites that are typically toxic or disrupt normal cellular function. The etiological relation of metabolic disorders has been uncovered through the study of metabolite amyloids. Various metabolites that accumulate in IEMs have been reported to self-assemble into organized structures. These structures exhibit similar physicochemical properties as proteinaceous amyloid fibrils. In this context, our study illustrated the aggregation properties of Branched chain amino acid (BCAA) i.e. Isoleucine, Leucine and Valine that accumulate in Maple syrup urine disease (MSUD) to investigate their propensities to assemble into amyloid-like fibrils. The structural morphologies of BCAA were studied via. microscopic techniques like Scanning electron microscopy (SEM), optical microscopy and phase contrast microscopy. Further, characterization techniques were employed to understand the physicochemical properties of the self-assemblies and its underlying mechanism. The amyloid-like nature of these aggregates was confirmed using Thioflavin T (ThT) and Congo Red (CR) assays, indicating a possible cytotoxic effect. The MTT assay reveals BCAAs were cytotoxic and significantly decrease cell viability. Our study plays a key role in understanding the physicochemical properties of MSUD in association to amyloid disease, possibly paving the way for the development of therapeutic solutions in the future. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/616096v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@13f26daorg.highwire.dtl.DTLVardef@10fdef5org.highwire.dtl.DTLVardef@f6e1d7org.highwire.dtl.DTLVardef@64f608_HPS_FORMAT_FIGEXP M_FIG C_FIG The self-assembly of BCAA-Ile, Leu, Val was investigated and the findings indicate that their aggregation may follow an amyloidogenic pathway.

bioengineering↗

bioRxiv2024

Designer DNA nanocages modulate anti-oxidative and anti-inflammatory responses in tumor associated macrophages

Cancer is a complex disease, with multiple treatment modalities, but no definitive cure. The tumor microenvironment contributes to the complexity of the disease by forming a niche of multiple cell types supporting each other to carry out various cellular functions. Tumor associated macrophages are one such kind of cells which support the tumor microenvironment via immunosuppression. DNA tetrahedron (TD), a widely explored DNA nanocage, has shown a lot of potential in therapeutics. However, the role of TD still remains quite unexplored in immunology. Here, we first establish the anti-oxidative and anti-inflammatory role of TD. We then proceed with using TD as a therapeutic agent in tumor associated macrophages by modulating the response of PD-L1. The findings of this work create a base for TD in biological applications such as cancer immunotherapy. Graphical AbstractImmunomodulatory effects of DNA nanocages on tumour associated macrophages O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/601504v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@10e585aorg.highwire.dtl.DTLVardef@ca91c4org.highwire.dtl.DTLVardef@12812a8org.highwire.dtl.DTLVardef@1e10880_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Programmable soft DNA hydrogels stimulate cellular endocytic pathways and proliferation

Hydrogels are pivotal in tissue engineering, regenerative medicine, and drug delivery applications. DNA molecules stand out among various biomaterials due to their unparalleled precision, programmability, and customization. In this study, we introduce a palate of novel cellular scaffolding platforms made of pure DNA-based hydrogel systems while improving the shortcomings of the existing platforms. DNA strands can form complex supramolecular branched structures essential for designing novel functional materials by its precise sequence-based self-assembly. These unique geometric scaffolds offer a soft, cushiony platform, ideal for culturing cells to mimic the complex native in vivo environments better. Each hydrogel comprises repeating units of branched DNA supramolecular structures, each possessing a distinct number of branching arms. The epithelial cells grown over these hydrogels show dynamic changes at multiple levels, from morphology to protein expression patterns, enhanced membrane traffic, and proliferation. The DNA hydrogels explored here are mechanically weak and soft and thus appropriate for applications in cell biology. This research lays the groundwork for developing a DNA hydrogel system with a higher dynamic range of stiffness, which will open exciting avenues for tissue engineering and beyond. Graphical abstract illustrating diverse branched DNA supramolecular architectures forming DNA hydrogels of various geometric profiles, each put to use in the cell culture applications. O_FIG O_LINKSMALLFIG WIDTH=160 HEIGHT=200 SRC="FIGDIR/small/595930v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1a3d4cborg.highwire.dtl.DTLVardef@e771cforg.highwire.dtl.DTLVardef@e0d5b4org.highwire.dtl.DTLVardef@ee42d3_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Self-assembled DNA-collagen bioactive scaffolds promote cellular uptake and neuronal differentiation

Different modalities of DNA-Collagen complexes have been utilized primarily for gene delivery studies. However, very few studies have investigated the potential of these complexes as bioactive scaffolds. Further, no studies have characterized the DNA-Collagen complex formed from the interaction of self-assembled DNA macrostructure and collagen. Towards this investigation, we report herein the fabrication of novel bioactive scaffolds formed from the interaction of sequence-specific, self-assembled DNA macrostructure and collagen type I. Varying molar ratios of DNA and collagen resulted in highly intertwined fibrous scaffolds with different fibrillar thicknesses. The formed scaffolds were biocompatible and presented as a soft matrix for cellular growth and proliferation. Cells cultured on DNA/Collagen scaffolds promoted enhanced cellular uptake of transferrin, and the potential of DNA/Collagen scaffolds to induce neuronal cell differentiation was further investigated. The DNA/Collagen scaffolds promoted neuronal differentiation of precursor cells with extensive neurite growth in comparison to control groups. These novel, self-assembled DNA/Collagen scaffolds could serve as a platform for the development of various bioactive scaffolds with potential applications in neuroscience, drug delivery, tissue engineering, and in vitro cell culture. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=137 HEIGHT=200 SRC="FIGDIR/small/595848v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@26e16aorg.highwire.dtl.DTLVardef@991d35org.highwire.dtl.DTLVardef@4c8909org.highwire.dtl.DTLVardef@b8ba55_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

2D MXene-DNA Hybrid Hydrogel for Thrombin Detection: A Versatile Approach for Biomedical Sensing

The delaminated MXene (2D MXene) and DNA hydrogel created enormous opportunities due to their versatility and ability to be tailored for specific applications. MXene offers high aspect ratio morphology and electrical conductivity, while DNA provides stimuli responsiveness and specificity in binding to ligands or complementary sequences. This synergy makes DNA an ideal actuator when combined with 2D MXenes. Present work makes the first effort to combine and exploit them for detecting the thrombin levels; a crucial proteolytic enzyme that plays a pivotal role in regulating blood clotting by cleaving fibrinogen into fibrin and plays a critical role in bleeding disorders such as Haemophilia and Von Willebrand disease. This study introduces a novel hybrid DNA hydrogel by leveraging the properties of 2D MXene with a thiol-modified thrombin binding aptamer (TBA) as a crosslinking agent. The TBA and its complementary DNA oligos are immobilized on 2D MXene sheets, forming a packed hydrogel. Upon thrombin binding, the TBA releases its complementary DNA, resulting in a loosened hydrogel and a change in resistance, which is used as a read-out for thrombin detection. The concept is successfully demonstrated, achieving 90-92% accuracy in detecting thrombin in artificial samples. This robust technique holds promise for biomedical sensing devices, allowing customization for the detection of various target molecules using specific aptamers.

bioengineering↗

bioRxiv2024

Cellular uptake and viability switch in the properties of lipid-coated carbon quantum dots for potential bioimaging and therapeutics

Carbon quantum dots derived from mango leaves exhibited bright red fluorescence. These negatively charged particles underwent coating with the positively charged lipid molecule N-[1-(2,3-dioleyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTMA). However, the bioconjugate displayed reduced uptake compared to the standalone mQDs in cancer cells (SUM 159A), and increased uptake in the case of epithelial (RPE-1) cells. Upon in vitro testing, the bioconjugate demonstrated a mitigating effect on the individual toxicity of both DOTMA and mQDs in SUM-159A (cancerous cells) and of DOTMA in RPE-1 cells. Conversely, it exhibited a proliferative effect on RPE-1 (epithelial cells). Surface modifications of QDs with lipids thus enhances their compatibility with biological systems, reducing systemic toxicity, minimizing off-site effects, sustaining drug release, and modulating cellular viability through various mechanisms (for example, apoptosis), which is, therefore, crucial for multiple applications such as targeted therapeutics. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/587464v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1eca201org.highwire.dtl.DTLVardef@7ff0a3org.highwire.dtl.DTLVardef@18f89b2org.highwire.dtl.DTLVardef@993b42_HPS_FORMAT_FIGEXP M_FIG C_FIG Red emitting, fluorescent carbon quantum dots synthesized using mango leaves(mQDs) showed enhanced cellular uptake and reduced cell viability in the case of cancer cells when compared with lipid-coated mQDs. However, in the case of non-cancerous cells, the lipid-coated mQDs showed enhanced cellular uptake and cell viability when compared with mQDs alone.

bioengineering↗

bioRxiv2024

Azadirachta indica: derived, red-emitting, carbon nanoparticles for cellular bioimaging and potential therapeutics

Red-emitting carbon nanoparticles (CNPs) were synthesized by the refluxed green synthesis method using ethanolic extract of neem leaves (Azadirachta indica). These nanoparticles were called as nQDs (neem quantum dots). The nQDs exhibited excellent photoluminescence properties with a maximum emission at 672nm, and the average size of nQDs was around 47nm. In the in-vitro study, Retinal Pigment epithelial (RPE1) cells and SUM159A cells showed enhanced cellular uptake. In RPE1 cells, the cellular uptake was higher than in SUM159A cells. In the biocompatibility assay, SUM159A cell viability declined with the increasing nQDs concentration. The results show that red-emissive CNPs can be synthesized from Azadirachta indica (neem) leaves using a simple method with a possible application in bioimaging and therapeutics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/582094v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@30da5aorg.highwire.dtl.DTLVardef@14f6fbcorg.highwire.dtl.DTLVardef@30e0f0org.highwire.dtl.DTLVardef@ffc962_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

DNA Tetrahedral Nanocages as a Promising Nanocarrier for Dopamine Delivery in Neurological Disorders

Dopamine is a neurotransmitter in the central nervous system that is essential for many bodily and mental processes, and a lack of it can cause Parkinsons disease. DNA tetrahedral (TD) nanocages are promising in bio-nanotechnology, especially as a nanocarrier. TD is highly programmable, biocompatible, and capable of cell differentiation and proliferation. It also has tissue and blood-brain barrier permeability, making it a powerful tool that could overcome potential barriers in treating neurological disorders. In this study, we used DNA-TD as a carrier for Dopamine to cells and zebrafish embryos. We investigated the mechanism of complexation between TD and dopamine hydrochloride using gel electrophoresis, fluorescence and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and molecular dynamic (MD) simulation tools. Further, we demonstrate these Dopamine-loaded DNA tetrahedral nanostructures cellular uptake and differentiation ability in SH-SY5Y neuroblastoma cells. Furthermore, we extended the study to zebrafish embryos as a model organism to examine survival and uptake. The research provides valuable insights into the complexation mechanism and cellular uptake of dopamine-loaded DNA tetrahedral nanostructures, paving the way for further advancements in nanomedicine for Parkinsons disease and other neurological disorders.

bioengineering↗

bioRxiv2023

Growth factor-induced desialylation for the fast control of endocytosis

It is commonly assumed that the glycan makeup of glycoproteins that reach the cell surface is final and static. Here, we challenge this notion by the discovery of a molecular switch that induces acute and reversible changes of glycans on the plasma membrane. We demonstrate that within minutes, the epidermal growth factor triggers the galectin-driven endocytosis of cell surface glycoproteins, such as integrins, that are key regulators of cell adhesion and migration. The onset of this process, mediated by the Na+/H+ antiporter NHE-1 and the neuraminidases Neu1/3, requires the pH-triggered enzymatic removal of sialic acids whose presence otherwise prevents galectin binding. Desialylated glycoproteins are then retrogradely transported to the Golgi apparatus where their glycan makeup is reset, and their function is repurposed to regulate EGF-dependent invasive cell migration. Glycosylation at the cell surface thereby emerges as a dynamic and reversible regulatory post-translational modification that controls a highly adaptable trafficking pathway.

cell biology↗