Biology subjects

Kumar, D. A.

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

3 recordsLinked to original sources

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↗