Crafting Designer Nanoreactors for Bioorthogonal Catalysis

Bio-orthogonal catalysis offers a highly versatile toolkit for biochemical modulation and capability to perform <i>new-to-nature</i> reactions inside living systems. It endows enormous opportunities to develop advanced platforms for augmented non-evolutionary functions, early disease-diagnosis, controlled drug release and precision medicine. Unfortunately, conventional catalyts have limitations such as bio-toxicity, hydrophobicity, poor reactivity and inability to control the reactions by remote stimuli. Our aim is to bridge the field of molecular synthesis with broader areas of biological and biomedical science by developing silica-based nanoreactors (NRs) where composition, morphologies, interfacial active-sites and microenvironment around different metals can be precisely controlled by novel nanospace-confined chemistries.^[1] We have designed and synthesized plasmonically integrated NRs (<i>PINRs</i>) with customizable structure and NIR-light-induced synergistic function for efficiently promoting intracellular catalytic reactions.^[2] <i>PINRs</i> consist of plasmonic corona comprising closely spaced Au-nanospheroids around the proximal and reactant-accessible silica-compartmentalized catalytic nanospace with different metal (Au/Pt/Pd) nanocrystals (NCs). Due to the highly coupled plasmonic antenna-effect, <i>PINRs</i> located inside the cytoplasmic region, can be remotely activated by NIR light to perform decaging reactions of masked molecular probes and pro-drugs. “<i>Nanocatalosome”</i>, a plasmonic Au-bilayer NR, where catalytic metals can be directly modified inside the semi-confined cavities in a unique interlayer nanospace.^[3] Such hierarchical vesicular designs can concentrate electromagnetic fields at numerous plasmonic hot-spots to promote reactions. Plasmonic-catalytic hybrid platforms are highly useful for photocatalysis but conventional thick catalytic metal-shells cause dramatic loss in quantum efficiency. To solve the issue, our NC-lamination strategy can functionalize NCs with a skin-like ultrathin few-atomic conformal metal layers, rendering the NRs with excellent photocatalytic performance.^[4] Besides NIR light, alternating magnetic field (AMF) is another benign source of energy. We designed magnetothermia-induced NR (<i>MAG-NR</i>) by selective growth of Pd-NCs on a preinstalled superparamagnetic iron-oxide core inside a hollow-porous silica nanoshell.^[5] <i>MAG-NRs</i> afforded opportunity to apply AMF to promote catalytic reactions inside living cells. By inventing solution-based and solid-state nanochemistries, different compositions, morphologies and architectures of silica nano-templates can be synthesized which can serve as tunable NR-platforms.^[1] A round bottom <i>jar</i>-like silica nanostructures (<i>SiJARs</i>) with a chemo-responsive metal-silicate <i>lid</i> is synthesized from a highly controlled solid-state NC-conversion process.^[6] In <i>SiJAR</i>, different catalytic noble metals were selectively modified on the <i>lid</i>-section through galvanic reactions and the <i>lid</i> aperture-opening was regulated by intracellular environment, accommodating the metals and enzymes inside an open-mouth NR for biorthogonal asymmertric chemo-enzymatic catalysis. Besides, an <i>yolk-shell</i> silica nano-template acted as dynamic cast for growing Au/Pt-based Janus NR, resembling to “egg-in-nest” morphology (<i>Au/Pt-ENs</i>).^[7] <i>Au/Pt-ENs</i> demonstrated chemotactic motion as a result of dual catalytic cascade in biomedia, and performed drug-delivery to cancer cells. As a future prospect, the field of biomedical engineering can hugely benefit by the aid of novel nanomaterials chemistry-based design and synthesis of engineered nano-devices and implants performing unique bioorhtogonal chemistry functions.<br/><br/>[1] <i>Acc. Chem. Res. </i><b>2018</b>,<i> 51, </i>2867–2879; [2]<i> ACS Catalysis</i> <b>2019</b>, 9, 977–990.; [3]<i> Angew. Chem. Int. Ed.</i> <b>2020</b>, <i>59</i>, 9460–9469.; [4] <i>J. Am. Chem. Soc.</i> <b>2021</b>, <i>143</i>, 10582–10589.; [5] <i>Nano Lett.</i> <b>2020</b>, <i>20, </i>6981–6988.; [6] <i>Angew. Chem. Int. Ed.</i> <b>2021</b>, <i>60</i>, 16337–16342; [7] <i>Angew. Chem. Int. Ed.</i> <b>2021</b>, <i>60</i>, 17579–17586.