Biology subjects

Dave, H.

Publications and source records attributed to Dave, H..

4 recordsLinked to original sources

bioRxiv2026

Hypoxia Induced Modulation of Cellular and in vivo uptake of DNA nanocage implications in therapeutics

DNA tetrahedra (DNA Td) are promising nanocarriers for drug delivery, but how hypoxia affects their cellular internalisation remains poorly understood. We synthesised and characterised Cy5-labelled DNA Td and established chemical hypoxia; in HeLa, MDA-MB-231, and MCF-7 cells. Hypoxia was confirmed by HIF-1; nuclear translocation. Confocal microscopy revealed significantly reduced DNA Td uptake under hypoxia, whereas transferrin and cholera toxin B uptake increased, indicating cargo-selective regulation. Temperature-arrest experiments confirmed reduced energy-dependent internalisation. Pharmacological profiling showed a shift from clathrin-mediated and galectin/glycan-dependent pathways toward lipid raft/cholesterol-dependent uptake. Hypoxia increased plasma membrane electronegativity, suggesting a biophysical barrier to DNA Td uptake. Importantly, DOTMA complexation restored uptake to normoxic levels, identifying electrostatic repulsion as a key determinant. In zebrafish larvae, hypoxia significantly enhanced whole-larva DNA Td accumulation. These findings highlight surface charge engineering as a strategy for improving DNA nanostructure delivery under hypoxic conditions.

bioinformatics↗

bioRxiv2026

Membrane sialylation orchestrates cellular gateways: A spatiotemporal analysis of cellular transport using DNA nanocages via membrane charge modulation

Negatively charged DNA nanostructures, such as tetrahedral nanocages, are internalized by cells despite the electrostatic repulsion from the anionic cell membrane, and, paradoxically, cancer cells, which carry intrinsically higher negative charge due to overexpression of sialic acids on their cell surface, show markedly higher uptake than normal cells. This contradiction exposes a fundamental gap in our understanding of how these anionic nanostructures overcome this repulsion. Using chemical modulation of cell-surface sialylation in RPE1 cells to create three groups with altered sialylation levels, together with inhibitor-based dissection of endocytic pathways, we demonstrate that an increase in cell surface sialylation governs the uptake of DNA tetrahedra not through electrostatics but by structurally remodeling the cell membrane via rearrangement of the GM1 lipid raft microdomain, recruiting caveolae-mediated endocytosis as an additional pathway alongside clathrin-mediated endocytosis, thereby increasing the intake of the nanostructure. These findings reframe tumor hyper-sialylation as a determinant of the uptake of anionic nanostructures, such as DNA tetrahedra, and as a targetable parameter for rational optimization of DNA-based nanotherapeutics against cancer. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/722926v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@10eede7org.highwire.dtl.DTLVardef@124dd56org.highwire.dtl.DTLVardef@13f5355org.highwire.dtl.DTLVardef@780ecf_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

Engineering pH-Responsive trans-Ferulic Acid/κ-Carrageenan Beads for On-Demand Micronutrient Delivery in Plants

Micronutrient deficiencies in soils are a critical challenge in agriculture, particularly in acidic soil environments where nutrient availability is strongly limited by fixation, leaching, and altered metal speciation. These constraints contribute to inefficient nutrient uptake and reduced crop yields. Conventional micronutrient supplementation methods are often inefficient, environmentally harmful, and unsustainable, underscoring the need for smarter delivery systems tailored to soil pH conditions. In this study, we developed biodegradable, pH-responsive microbeads from {kappa}-carrageenan ({kappa}-CG) and trans-ferulic acid (TFA) for targeted micronutrient release. The {kappa}-CG-TFA microbeads were synthesized via an eco-friendly process and optimized for size, morphology, stability, and nutrient retention. Characterization confirmed the successful incorporation of functional groups, while swelling, degradation, and release studies demonstrated efficient delivery of essential micronutrients (Mn2+, Zn2+, Cu2+, and Fe3+) under acidic conditions (pH 4.0), mimicking acidic soil environments. The inherent antioxidant activity of TFA conferred strong radical-scavenging capacity, further enhancing its functionality. Soil water and plant growth assays revealed that the microbeads improved micronutrient availability, significantly increased chlorophyll content and leaf area, promoted vigorous seedling growth, and caused no phytotoxic effects. Collectively, these findings establish {kappa}-CG-TFA microbeads as a promising, eco-friendly platform for sustainable micronutrient delivery and stress reduction, thereby improving crop productivity in agriculture.

bioengineering↗

bioRxiv2020

Development of a small molecule that corrects misfolding and increases secretion of Z α1-antitrypsin

Severe 1-antitrypsin deficiency results from the Z allele (Glu342Lys) that causes the accumulation of homopolymers of mutant 1-antitrypsin within the endoplasmic reticulum of hepatocytes in association with liver disease. We have used a DNA-encoded chemical library to undertake a high throughput screen to identify small molecules that bind to, and stabilise Z 1-antitrypsin. The lead compound blocks Z 1-antitrypsin polymerisation in vitro, reduces intracellular polymerisation and increases the secretion of Z 1-antitrypsin three-fold in mammalian cells including an iPSC model of disease. Crystallographic and biophysical analyses demonstrate that GSK716 and related molecules bind to a cryptic binding pocket, negate the local effects of the Z mutation and stabilise the bound state against progression along the polymerization pathway. Oral dosing of transgenic mice at 100 mg/kg three times a day for 20 days increased the secretion of Z 1-antitrypsin into the plasma by 7-fold. There was no observable clearance of hepatic inclusions with respect to controls. This study provides proof-of-principle that mutation ameliorating small molecules are a viable approach to treat protein conformational diseases.

pharmacology and toxicology↗