Plasmonic-Assisted Thermocyclizations in Living Cells Using Metal-Organic Framework Based Nanoreactors.

Carolina Carrillo-Carrión,María Tomás-Gamasa,Pablo Del Pino,Beatriz Pelaz,Manuel Ceballos,Fernando López,Raquel Martínez,José L Mascareñas,Paolo Destito,Ester Polo

doi:10.1021/acsnano.1c07983

Abstract

We describe a microporous plasmonic nanoreactor to carry out designed near-infrared (NIR)-driven photothermal cyclizations inside living cells. As a proof of concept, we chose an intramolecular cyclization that is based on the nucleophilic attack of a pyridine onto an electrophilic carbon, a process that requires high activation energies and is typically achieved in bulk solution by heating at ∼90 °C. The core–shell nanoreactor (NR) has been designed to include a gold nanostar core, which is embedded within a metal–organic framework (MOF) based on a polymer-stabilized zeolitic imidazole framework-8 (ZIF-8). Once accumulated inside living cells, the MOF-based cloak of NRs allows an efficient diffusion of reactants into the plasmonic chamber, where they undergo the transformation upon near-IR illumination. The photothermal-driven reaction enables the intracellular generation of cyclic fluorescent products that can be tracked using fluorescence microscopy. The strategy may find different type of applications, such as for the spatio-temporal activation of prodrugs.

Highlights

We describe a microporous plasmonic nanoreactor to carry out designed near-infrared (NIR)-driven photothermal cyclizations inside living cells
We have comprehensively characterized the physicochemical properties of inorganic nanoparticles equipped with zeolitic imidazole framework-8 (ZIF-8)/PMA coatings in a previous work.[23,36]
Different metal−organic framework (MOF)-based combinations have been proposed for thermoplasmonic catalysis in solar energy conversion.[38]

Summary

Introduction

We describe a microporous plasmonic nanoreactor to carry out designed near-infrared (NIR)-driven photothermal cyclizations inside living cells. Living cells respond to external signals through cascades of connected chemical reactions that take place at physiological temperatures Most of these reactions are catalyzed by enzymes and have been selected by evolution to ensure an appropriate functioning of living organisms.[1] A major current goal in chemical and cell biology consists of the discovery of chemically engineered, intracellular reactions that allow to implement non-native functions, thereby influencing the properties of cells in a predictable manner.[2] The last two decades have witnessed sustained progress in the development of a variety of bio-orthogonal and biocompatible reactions, most of which are based on the use of strained reactants[3−5] or of metal catalysts.[6−11] Some of these reactions have already allowed impressive applications either in the activation of prodrugs,[12−15] or in interrogating biological processes.[16] these approaches are not devoid of important limitations, such as the intrinsic reactivity of the strained reactants, or the problems of biocompatibility and efficiency of the metal-based reagents.[2]. It deals with a typical uncaging that might be alternatively performed with palladium catalysts[34] or with NP-based gold catalysts without light stimulation.[35]

Methods

Results

Conclusion