Guanosine-based supramolecular particles for enhanced drug and gene delivery in cell culture

05 February 2025, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Supramolecular hacky sacks (SHS) are a novel class of self-assembled colloidal particles formed from guanosine (G) derivatives, designed to function as versatile tools for cellular and therapeutic applications. Here, we investigate the structure-dependent cellular uptake, intracellular trafficking, and functional performance of SHS particles. Confocal microscopy and flow cytometry studies reveal that SHS uptake is highly dependent on the composition of the G-derivatives, suggesting selective interactions with cellular pathways. Importantly, we demonstrate that SHS particles serve as a biocompatible platform for drug and gene delivery, effectively encapsulating and releasing doxorubicin for enhanced cytotoxicity, as well as facilitating plasmid transfection with sustained fluorescent protein expression. These results establish SHS particles as a versatile biocompatible platform with tunable bioactivity, offering new opportunities for the application of supramolecular assemblies in drug delivery and gene therapy. The inherent biodegradability, simplicity of synthesis, and versatility of SHS particles underscore their potential as next-generation biomaterials for biomedical applications.

Keywords

supramolecular biomaterials
guanosine self-assembly
drug delivery systems
gene transfection
biocompatible nanomaterials
supramolecular G-quadruplexes
controlled drug release

Supplementary materials

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Supporting Information file
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A 26-page Supporting Information file to accompany the main manuscript, providing additional experimental details, extended data analysis, and supplementary figures that further substantiate our findings.
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