The folding of certain proteins (e.g., enzymes) into perfectly defined 3D conformations via multi-orthogonal interactions is critical to their function. Concerning synthetic polymers chains, the “folding” of individual polymer chains at high dilution via intra-chain interactions leads to so-called single-chain nanoparticles (SCNPs). This review article describes the advances carried out in recent years in the folding of single polymer chains into discrete SCNPs via multi-orthogonal interactions using different reactive chemical species where intra-chain bonding only occurs between groups of the same species. First, we summarize results from computer simulations of multi-orthogonally folded SCNPs. Next, we comprehensively review multi-orthogonally folded SCNPs synthesized via either non-covalent bonds or covalent interactions. Finally, we conclude by summarizing recent research about multi-orthogonally folded SCNPs prepared through both reversible (dynamic) and permanent bonds.

Clean use of photons from light to activate chemical reactions offers many possibilities in different fields, from chemistry and biology to materials science and medicine. This review article describes the advances carried out in last decades toward the phototriggered synthesis of single-chain polymer nanoparticles (SCNPs) as soft nanomaterials with promising applications in enzyme-mimicking catalysis and nanomedicine, among other different uses. First, we summarize some different strategies developed to synthesize SCNPs based on photoactivated intrachain homocoupling, phototriggered intrachain heterocoupling and photogenerated collapse induced by an external cross-linker. Next, we comprehensively review the emergent topic of photoactivated multifolding applied to SCNP construction. Finally, we conclude by summarizing recent strategies towards phototriggered disassembly of SCNPs.

The folding of certain proteins (e.g., enzymes) into perfectly defined 3D conformations via multi-orthogonal interactions is critical to their function. Concerning synthetic polymers chains, the “folding” of individual polymer chains at high dilution via intra-chain interactions leads to so-called single-chain nanoparticles (SCNPs). This review article describes the advances carried out in recent years in the folding of single polymer chains into discrete SCNPs via multi-orthogonal interactions using different reactive chemical species where intra-chain bonding only occurs between groups of the same species. First, we summarize results from computer simulations of multi-orthogonally folded SCNPs. Next, we comprehensively review multi-orthogonally folded SCNPs synthesized via either non-covalent bonds or covalent interactions. Finally, we conclude by summarizing recent research about multi-orthogonally folded SCNPs prepared through both reversible (dynamic) and permanent bonds.

Clean use of photons from light to activate chemical reactions offer many possibilities in different fields, from chemistry and biology to materials science and medicine. This review article describes the advances carried out in last decades toward the phototriggered synthesis of single-chain polymer nanoparticles (SCNPs) as soft nanomaterials with promising applications in enzyme-mimicking catalysis and nanomedicine, among other different uses. First, we summarize different strategies developed to synthesize SCNPs based on photoactivated intrachain homocoupling, phototriggered intrachain heterocoupling and photogenerated collapse induced by external cross-linker. Next, we comprehensively review the emergent topic of photoactivated multifolding applied to SCNP construction. Finally, we conclude by summarizing recent strategies towards phototriggered disassembly of SCNPs.

We report herein on a new platform for synthesizing stable, inert, and dispersible metal-free single-chain nanoparticles (SCNPs) via intramolecular metal-traceless azide–alkyne click chemistry. It is well known that SCNPs synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) often experience metal-induced aggregation issues during storage. Moreover, the presence of metal traces limits its use in a number of potential applications. To address these problems, we selected a bifunctional cross-linker molecule, sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DIBOD). DIBOD has two highly strained alkyne bonds that allow for the synthesis of metal-free SCNPs. We demonstrate the utility of this new approach by synthesizing metal-free polystyrene (PS)-SCNPs without significant aggregation issues during storage, as demonstrated by small-angle X-ray scattering (SAXS) experiments. Notably, this method paves the way for the synthesis of long-term-dispersible, metal-free SCNPs from potentially any polymer precursor decorated with azide functional groups.