Saleeem, S. | Search bioRxiv

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↗

bioRxiv2022

Scavenger receptor B1 facilitates the endocytosis of Escherichia coli via TLR4 signaling in mammary gland infection

SCARB1 belongs to class B of Scavenger receptors (SRs) that are known to be involved in binding and endocytosis of various pathogens. SRs have emerging role in regulating innate immunity and host-pathogen interactions by acting in co-ordination with Toll-like receptors. Little is known about the function of SCARB1 in milk-derived mammary epithelial cells (MECs). This study reports the role of SCARB1 in infection and its potential association in TLR4 signaling on bacterial challenge in Goat mammary epithelial cells (GMECs). The novelty in the establishment of MEC culture lies in the method that aims to enhance the viability of the cells with intact characteristics upto a higher passage number. We represent MEC culture to be used as a potential infection model for deeper understanding of animal physiology especially around the mammary gland. On E.coli challenge the expression of SCARB1 was significant in induced GMECs at 6 h. Endoribonuclease-esiRNA based silencing of SCARB1 affects the expression of TLR4 and its pathways i.e. MyD88 and TRIF pathways on infection. Knockdown also affected the endocytosis of E.coli in GMECs demonstrating that E.coli uses SCARB1 function to gain entry in cells. Furthermore, we predict 3 unique protein structures of uncharacterized SCARB1 (Capra hircus) protein. Overall, we highlight SCARB1 as a main participant in host defence and its function in antibacterial advances to check mammary gland infections.

immunology↗