Biology subjects

Kumar, D. A.

Publications and source records attributed to Kumar, D. A..

6 recordsLinked to original sources

bioRxiv2026

Programmable DNA Nanocages Enhance Levodopa Delivery for Neuroprotection in a Zebrafish Model of Parkinson's Disease

Parkinsons Disease (PD) is the second-most prevalent neurodegenerative disease, often characterized by neural motor dysfunction, oxidative stress, and dopamine receptor malfunction leading to improper dopamine levels in the system. DNA tetrahedron nanostructures are a promising drug delivery agent due to their biocompatibility and properties of controlled and sustained release. In this study we evaluated the potential of using TD-mediated Levodopa delivery for a MPTP induced Parkinsons Disease model in Zebrafish larvae. The induction of Parkinsonism led to morphological behaviour changes like the presence of tremors, erratic swimming behaviour, latency, and reduced locomotor activity, even elevated reactive oxygen species (ROS) and apoptosis was observed. These effects and symptoms were alleviated when the larvae were treated using TD:Levodopa conjugates, particularly at the 1:100 ratio. At the molecular level, genes like TH, DAT, SOX2, PARKIN and apoptotic genes like BCL2 and caspases showed alteration in expression in the Parkinsonism model and post treatment was induced. This highlights the potential of using DNA nanocages as a novel drug delivery agent as therapeutic strategy for Parkinsons disease. TOCDopamine loaded DNA nanocages with the capacity to overcome biological barriers for release of dopamine with neuroprotection activity in Parkinsons disease model of zebrafish. O_FIG O_LINKSMALLFIG WIDTH=193 HEIGHT=200 SRC="FIGDIR/small/742731v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1d2b94eorg.highwire.dtl.DTLVardef@183bc1aorg.highwire.dtl.DTLVardef@1b254ddorg.highwire.dtl.DTLVardef@e1b589_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

Green Synthesis of Fluorescent Carbon Quantum Dots from Bearberry Extract via Hydrothermal and Microwave-Assisted Routes: Comparative Physicochemical Characterisation, Antioxidant Activity, and Biocompatibility Evaluation

Producing photoluminescent nanomaterials with controllable surface chemistry and predictable biological activity remains one of the outstanding problems in green nanoscience. The present study shows that, even when the same bearberry (Arctostaphylos uva-ursi) extract precursor is used, the mode of energy delivery during synthesis plays a determining role in shaping the surface composition, photophysical properties, and biological activity of the resulting carbon quantum dots (CQDs). Hydrothermal processing at 160 {degrees}C for 6 h yielded CQDs with an average particle size of 7.13 nm. Surface characterisation indicated abundant hydroxyl- and carbonyl-containing functionalities, while XPS analysis showed a comparatively higher proportion of graphitic sp2 carbon (43.06%). These structural features were accompanied by strong DPPH free-radical scavenging activity. Microwave-assisted synthesis, by contrast, yields 9.65 nm particles carrying a substantially greater surface carboxylate content (O-C=O: 19.06%), a higher fluorescence quantum yield, and enhanced intracellular uptake statistically significant in retinal epithelial cells at 200 {micro}g/mL (p < 0.001) and showing concentration-dependent accumulation in zebrafish larvae from 100 {micro}g/mL onwards (p < 0.05). XPS C 1s deconvolution, interpreted alongside FTIR difference spectroscopy, points to incomplete decarboxylation under microwave conditions as the primary mechanistic origin of these divergent properties. Cytocompatibility was uncompromised for both formulations across the full concentration range tested (10-250 {micro}g/mL) in RPE-1 and HeLa cells, with no statistically significant loss of viability at any concentration. Taken together, these results define a synthesis-route-encoded structure-property relationship that permits rational selection between an antioxidant-optimised and an imaging-optimised CQD formulation from the same green precursor feedstock.

bioengineering↗

bioRxiv2026

Hamelia patens-Derived Red-Emitting Carbon Quantum Dots: Surface-State Luminescence, Antioxidant Potency, and In Vitro Bioimaging

Red-emitting carbon quantum dots (HP-CQDs) were synthesised for the first time from aqueous leaf extracts of Hamelia patens through single-step, reagent-free microwave-assisted carbonisation (750 W). The resulting nanoparticles displayed a narrow hydrodynamic size distribution centred at 3.9 nm, consistent with atomic force microscopy measurements showing a maximum height of 2.81 nm. Under 400 nm excitation, the CQDs exhibited a characteristic red emission maximum at 675 nm, representing a rare example of long-wavelength-emitting green CQDs derived from plant biomass. UV-Vis absorption bands at 224 and 256 nm were assigned to {pi}-{pi}* transitions of aromatic carbon domains and n-{pi}* transitions associated with carbonyl-containing surface groups, respectively. X-ray photoelectron spectroscopy (XPS) indicated a carbon-rich composition (C: 67.24%, O: 31.25%, N: 1.52%) with prominent C-O (42.67%) and C-C/C=C (42.64%) contributions. ATR-FTIR further confirmed the retention of hydroxyl, ether, and aliphatic functionalities following carbonisation. The excitation-wavelength-independent emission peak position implicates discrete surface molecular states rather than a heterogeneous distribution of emitters. HP-CQDs exhibit potent DPPH radical scavenging activity (ICOO = 141.8 {micro}g mLO{superscript 1}), comparable to ascorbic acid (ICOO = 114.8 {micro}g mLO{superscript 1}), and maintain >95% cell viability in both HeLa and RPE-1 cells up to 250 {micro}g mLO{superscript 1}. Confocal microscopy demonstrates concentration-dependent cytoplasmic accumulation and selective perinuclear localization at 300 {micro}g mLO{superscript 1}. In vivo biodistribution in zebrafish larvae confirms systemic uptake with statistically significant fluorescence enhancement at 500 {micro}g mLO{superscript 1} (p < 0.01), establishing HP-CQDs as biocompatible red-fluorescent probes with dual imaging-antioxidant functionality. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/724069v2_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@17be668org.highwire.dtl.DTLVardef@153d874org.highwire.dtl.DTLVardef@1a7e6edorg.highwire.dtl.DTLVardef@29f13a_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Growth-factor ligand functionalization enhances cellular and in vivo uptake of DNA nanodevices

Epidermal Growth Factor (EGF) and Transforming Growth Factor beta (TGF-{beta}) are two important classes of growth factor that regulates cell growth, cell proliferation, differentiation, immune responses, and extracellular matrix generation. Using a short peptide-based ligand coupled to DNA nanocages, we present the enhanced internalization of a receptor-mediated peptide-DNA nanocage. We used here tdDNA as a delivery vehicle. Our study in cellular and in vivo showed excellent internalization, cell growth, and inhibition. We expect that a tdDNA-modified receptor-binding peptides could become a valuable scaffold for use as a cellular programming and regenerative material.

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↗