Biology subjects

Vaswani, P.

Publications and source records attributed to Vaswani, P..

9 recordsLinked to original sources

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

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

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↗

bioRxiv2023

DNA tetrahedron as a carrier of doxorubicin for metastatic breast cancer treatment

Metastatic breast cancer is a significant clinical challenge calling for novel and efficient therapeutic approaches. DNA tetrahedron, a highly programmable nanocage, offers some promising attributes including biocompatibility, stability, and functionalization making it an attractive candidate for drug delivery. In this study, we have explored the potential of DNA tetrahedron as a carrier of doxorubicin, a DNA and RNA synthesis-inhibiting chemotherapy drug. We have encapsulated doxorubicin in DNA tetrahedron (TD: Dox) and subsequently focused on metastatic breast cancer cells for the effect of the same. We showed that TD: Dox has the potential to inhibit the migration of cancerous cells in the 2D model and inhibit the invasion of tumor cells in the 3D model as well. This system also can be uptaken in in vivo zebrafish model as well. Overall, this study promises the TD: Dox system as an ideal drug delivery model and a viable approach for metastatic breast cancer treatment.

bioengineering↗

bioRxiv2023

Red Fluorescent Carbon Nanoparticles Derived from Spinacia oleracea L.: A Versatile Tool for Bioimaging & Biomedical Applications

Carbon-based fluorescent quantum dots are an emerging class of nanoparticles for targeted bioimaging and biomedical applications. We present a facile microwave-assisted approach for synthesizing carbon nanoparticles with bright red fluorescence using ethanolic extracts of Spinacia oleracea leaves, with a quantum yield of 94.67%. These nanoparticles, called CNPs, ranging from 15-50 nm, demonstrated fluorescence emission in the near-infrared (NIR) region between 650 and 700 nm, independent of excitation wavelength. Upon excitation at a wavelength of 410 nm, they exhibit an emission maxima peak at 672 nm. The significant uptake of CNPs in mammalian cells and zebrafish larvae highlights their potential as bioimaging agents in diverse biomedical applications in vivo. Further, these quantum dots enhance cellular proliferation and migration as observed by wound healing assay in mammalian cells, indicating their possible application in tissue engineering and regenerative medicine. These findings suggest that biosynthesized carbon nanoparticles possess significant potential for biomedical activities, which can serve as a robust benchmark for researchers towards promoting sustainability.

bioengineering↗

bioRxiv2022

Self-assembled DNA nanostructures promote cell migration & differentiation of human umbilical vein endothelial cells

DNA nanostructures have been explored for capabilities to influence cellular behavior and its functions. Recent times have seen the development of new emergent functionalities of DNA nanodevices as class of biomaterials with immense capacity to interface with biological systems and having vast potential in disease diagnosis and therapeutics. Being chemically robust and biocompatible in nature, DNA nanostructures have been surface modified and structurally fine-tuned to find emerging applications in the field of stem cell therapy and tissue regeneration. DNA nanostructures can be utilized for therapeutic angiogenesis that involves induction of blood vessel formation and can be used to treat ischemic diseases like stroke or heart failure. This work addresses the effect of DNA nanostructures structural topology in their capacity to stimulate endothelial cells angiogenesis. We tested a panel of four geometries of DNA nanostructure and checked their potential on the differentiation of human umbilical vein endothelial cells (HUVECs). While different DNA nanostructure geometries showed successful angiogenesis induction and cell migration in HUVECs, tetrahedral DNA cages showed the maximum uptake and angiogenesis potential indicating that not only the composition of materials, but also the 3D arrangement of ligands might also play role in stimulating the angiogenesis process.

bioengineering↗

bioRxiv2021

Ligand geometry dictates cellular and in vivo uptake of 3D DNA nanostructures

Fabrication of nanoscale DNA devices to generate 3D nano-objects with precise control of shape, size, and presentation of ligands has shown tremendous potential for therapeutic applications. The interactions between different topologies of 3D DNA nanostructures and the cell membranes are crucial for designing efficient tools for interfacing DNA devices with biological systems. The practical applications of these DNA nanocages are still limited in cellular and biological systems owing to the limited understanding of interactions of different surface topologies of DNA nanodevices with cell membranes. The correlation between the geometry of DNA nanostructures and their internalization efficiency remains elusive. We investigated the influence of the shape and size of 3D DNA nanostructure on their cellular internalization efficiency. We found that of different geometries designed, one particular geometry, i.e., the tetrahedral shape, is more favoured over other geometries for their cellular uptake in 2D and 3D cell models. This is also replicable for cellular processes like 3D cell invasion assays in 3D spheroid models and passing the epithelial barriers in in-vivo zebrafish model systems. Our work establishes ground rules for the rational designing of DNA nanodevices for their upcoming biological and biomedical applications.

bioengineering↗

bioRxiv2021

Water soluble, red emitting, carbon nanoparticles stimulate 3D cell invasion via clathrin-mediated endocytic uptake

Bright, fluorescent nanoparticles with excitation and emission towards the red end of the spectrum are highly desirable in the field of bioimaging. We present here a new class of organic carbon-based nanoparticles (CNPs) with robust quantum yield and fluorescence towards the red region of the spectrum. Using organic substrates like para-phenylenediamine (PPDA) dispersed in diphenyl ether and reflux conditions, we achieved scalable amounts of CNPs of the average size of 25 nm. These CNPs were readily uptaken by different mammalian cells, and we show that they prefer clathrin-mediated endocytosis for their cellular entry route. Not only can these CNPs be specifically uptaken in cells, but they also stimulate cellular processes like cell invasion from 3D spheroid models. These new class of CNPs, which have sizes similar to proteinaceous ligands, hold immense potential for their surface functionalization, whereby they could be explored as promising bioimaging agents for biomedical imaging and intracellular drug delivery.

bioengineering↗