Biology subjects

Gothelf, K. V.

Publications and source records attributed to Gothelf, K. V..

3 recordsLinked to original sources

bioRxiv2025

Highly controllable co-delivery of siRNA and doxorubicin via cationic niosomes for synergistic anticancer effects

The combination of anticancer drugs and siRNA has emerged as a promising strategy for cancer therapy due to their synergistic effects. However, a major challenge is developing a co-delivery system with high controllability capable of simultaneously encapsulating both the chemical drug and siRNA. In this study, we developed a simple and highly controllable co-delivery system for delivering Doxorubicin (Dox) and siRNA. Co-encapsulation was achieved by intercalating Dox into duplex GC-rich oligodeoxynucleotides, (CGA)7/(TCG)7 (termed CGA-Dox), followed by mixing with siRNA and subsequent condensation using a cationic noisome (SPN) through electrostatic interactions. SPN/siRNA/Dox exhibited efficient cellular uptake and high gene silencing efficiency in both H1299 and MDA-MB-231 cells. Furthermore, co-delivery of Dox and siRNA targeting ribonucleotide reductase subunit M2 (RRM2) using this system significantly enhanced cellular apoptosis and antiproliferative effect in MDA-MB-231 cells compared to Dox alone. These results indicate that our co-delivery system constructed via Dox-DNA intercalation and electrostatic complexation, represents a promising strategy for synergistic anticancer therapy.

bioengineering↗

bioRxiv2025

Enzyme-powered DNA origami nanostructures for enhanced mucosal diffusion

Crossing mucosal barriers is a central challenge for oral drug delivery, where nanoparticle design must balance stability with mobility in complex fluids. Here, we demonstrate DNA origami as a programmable platform to investigate these processes. Using FRET analysis, we show that DNA nanostructures retain their structural integrity for extended periods in porcine intestinal fluid and mucus, establishing their suitability for biologically relevant environments. Building on this, we used single-particle tracking to assess enzyme-powered propulsion within mucus. Both urease and catalase enhanced diffusion only when anchored to the DNA origami structure, with propulsion persisting for tens of minutes. Importantly, enzyme spatial organization dictated performance: symmetric urease placement improved mobility via uniform local pH shifts, while asymmetric catalase placement enabled efficient bubble-driven propulsion. These results highlight DNA origami as a uniquely versatile tool to dissect structure-function relationships in mucus transport and provide design principles for next-generation, enzyme-powered oral delivery systems.

bioengineering↗

bioRxiv2025

Bacteriophage-Mimetic DNA Origami Needle for Targeted Membrane Penetration and Cytosolic Cargo Delivery

Inspired by the natural ability of bacteriophages to deliver genetic material directly into host cells, we employed a bottom-up approach to construct a multifunctional synthetic DNA origami needle-like structure. This origami is functionalized with trastuzumab antibodies, cholesterol, protective polymers, and two dyes, which together enable selective targeting and insertion into SKBR3 cancer cells. A disulfide-linked dye payload was attached to the apex of the needle, allowing controlled release in the cytoplasm triggered by the high intracellular glutathione concentration. Real-time tracking of the payload confirmed both successful targeting of the origami structure and subsequent direct cytosolic delivery. By mimicking fundamental mechanisms of bacteriophages, we propose that this artificial needle structure can serve as a prototypical device for the targeted delivery of small-molecule drugs directly into the cytosol.

biochemistry↗