Co-assembly nanoreactor protocol for the efficient synthesis of single-chain nanoparticles

Single-chain nanoparticles (SCNPs) show great promise in biomedical applications, due to their unique properties in ultra-small size, high porosity, and ease of functionalization. Traditional synthesis protocols for SCNPs often result in high polydispersity of size and deviations from globular compact conformations, accompanied by challenges such as high energy consumption and low yield. By means of simulation, we propose an innovative method for the synthesis of SCNPs through a co-assembly nanoreactor. This protocol adeptly avoids intermolecular aggregation of the precursor chain under poor solvent conditions by crosslinking inside the central cavity of nanoreactors formed by co-assembled nanorods, significantly enhancing the quality and efficiency of the SCNP synthesis. Our results pave the way for the synthesis of SCNP with highly controllable size/topology, with potential applications in nanocarrier, drug delivery, and cell uptake, among other fields. [Display omitted] •An innovative method for the synthesis of SCNPs through a co-assembly nanoreactor is proposed via molecular dynamics simulations.•This method can effectively prevent intermolecular coupling of the precursor chains in poor solvent.•The resulted SCNPs maintain a narrow size distribution and globular compact conformations.•The proposed method guarantees high-quality preparation of SCNPs at high polymer concentrations.