From Bench to Cell: A Roadmap for Assessing the Bioorthogonal “Click” Reactivity of Magnetic Nanoparticles for Cell Surface Engineering

Abstract

In this work, we report the use of bioorthogonal chemistry, specifically the strain-promoted click azide–alkyne cycloaddition (SPAAC) for the covalent attachment of magnetic nanoparticles (MNPs) on living cell membranes. Four types of MNPs were prepared, functionalized with two different stabilizing/passivation agents (a polyethylene glycol derivative and a glucopyranoside derivative, respectively) and two types of strained alkynes with different reactivities: a cyclooctyne (CO) derivative and a dibenzocyclooctyne (DBCO) derivative. The MNPs were extensively characterized in terms of physicochemical characteristics, colloidal stability, and click reactivity in suspension. Then, the reactivity of the MNPs toward azide-modified surfaces was evaluated as a closer approach to their final application in a living cell scenario. Finally, the DBCO-modified MNPs, showing superior reactivity in suspension and on surfaces, were selected for cell membrane immobilization via the SPAAC reaction on the membranes of cells engineered to express azide artificial reporters. Overall, our work provides useful insights into the appropriate surface engineering of nanoparticles to ensure a high performance in terms of bioorthogonal reactivity for biological applications.

Bioorthogonal chemistry of polyoxometalates – challenges and prospects

“…The related concept, involving supramolecular protection followed by strain-promoted click conjugation, has recently been demonstrated for the bioorthogonal attachment of magnetic nanoparticles to cell membranes. 52 Our Perspective focuses on the challenges and prospects of introducing, implementing, and adapting (post)functionalized POMs 9,12,53 to accelerate progress in the development of their bioorthogonal chemistry. hybrid compounds.…”

Química bioortogonal: cuando los organismos vivos se convierten en matraces de reacción

“…Por su parte, la química click en combinación con métodos capaces de introducir receptores artificiales en la membrana de células tumorales, de forma controlada y con independencia del tipo de célula (por ejemplo, a través de glicoingeniería metabólica, como se ha descrito anteriormente), permite superar estas limitaciones y abordar en mejores condiciones la vectorización de las NP hacia las células diana. 5,48 El concepto de etiquetado universal de células tumorales mediante glicoingeniería metabólica se describe en la Figura 8.…”

Bioorthogonal Chemistry of Polyoxometalates – Challenges and Prospects

“…The related concept, involving supramolecular protection followed by strain-promoted "click" conjugation, has recently been demonstrated for the bioorthogonal attachment of magnetic nanoparticles to cell membranes. 48 This Perspective focuses on the challenges and prospects of incorporation, implementation and adaptation of (post)functionalized POMs 9,12,49 to give rise to their efficient bioorthogonal chemistry.…”