Laboratoire des biomateriaux programmables

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Publications associées (34)

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Selective integrin targeting with DNA-based nanomaterials

Eva Eugene Kurisinkal

Targeting cells specific to type and state remains a challenge in developing effective therapies, sensitive diagnostics, also robust and versatile tissue engineering. A promising strategy is to focuses on improving the inherent selectivity of the targeting system through precise orchestration of ligand-receptor interactions. Integrin receptors present themselves as a strategic target as their expression has been reported to be regulated across cell types and states. The principle of super-selectivity permits the selective targeting of integrin receptors above a threshold concentration in high valency and relative low affinity systems, leaving sparser counterparts unaffected. Here, we demonstrate that DNA based scaffolds with rigid ligand nanoscale spatial presentation can be designed to discriminate between adhesions by varying RGD ligand spacing targeting integrin âº5Î²1 receptors. We begin by modelling integrin âº5Î²1 receptors nearest neighbour distributions across HUVEC, CHO and HeLa cells. Targeting spacings in the sub-60nm reveal trends in binding efficacies based on cell type and activation state. An ensuing study of HUVEC response to local ligand geometries of varying global inter-geometry spacings presented on higher valency DNA scaffolds randomly immobilised result in two distinct adhesion cluster formations. Our findings open avenues in the design of super-selective targeting elements, besides providing insight on the regulation of integrin receptors on the cell surface across different cell types. Parameters for ligand presentation at the sub-adhesion scale affords selective cell engagement in biomaterial presentation.

EPFL2022

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DNA-Liposome Hybrid Carriers for Triggered Cargo Release

Diana Kornelia Morzy

The design of simple and versatile synthetic routes to accomplish triggered-release properties in carriers is of particular interest for drug delivery purposes. In this context, the programmability and adaptability of DNA nanoarchitectures in combination with liposomes have great potential to render biocompatible hybrid carriers for triggered cargo release. We present an approach to form a DNA mesh on large unilamellar liposomes incorporating a stimuli-responsive DNA building block. Upon incubation with a single-stranded DNA trigger sequence, a hairpin closes, and the DNA building block is allowed to self-contract. We demonstrate the actuation of this building block by single-molecule Forster resonance energy transfer (FRET), fluorescence recovery after photobleaching, and fluorescence quenching measurements. By triggering this process, we demonstrate the elevated release of the dye calcein from the DNA- liposome hybrid carriers. Interestingly, the incubation of the doxorubicin-laden active hybrid carrier with HEK293T cells suggests increased cytotoxicity relative to a control carrier without the triggered-release mechanism. In the future, the trigger could be provided by peritumoral nucleic acid sequences and lead to site-selective release of encapsulated chemotherapeutics.

AMER CHEMICAL SOC2022

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DNA-based nanomaterials are gaining popularity as uniform and programmable bioengineering tools as a result of recent solutions to their weak stability under biological conditions. The DNA nanotechnology platform uniquely allows decoupling of engineering parameters to comprehensively study the effect of each upon cellular encounter. We here present a systematic analysis of the effect of surface parameters of DNA-based nanoparticles on uptake in three different cell models: tumor cells, macrophages, and dendritic cells. The influence of surface charge, stabilizing coating, fluorophore types, functionalization technique, and particle concentration employed is found to cause significant differences in material uptake among these cell types. We therefore provide new insights into the large variance in cell type-specific uptake, highlighting the necessity of proper engineering and careful assay development when DNA-based materials are used as tools in bioengineering and as future nanotherapeutic agents.

AMER CHEMICAL SOC2022

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