There is a real need for new antibiotics against self‐evolving bacteria. One option is to use biofriendly broad‐spectrum and mechanically tunable antimicrobial hydrogels that can combat multidrug‐resistant microbes. Whilst appealing, there are currently limited options. Herein, broad‐spectrum antimicrobial biometallohydrogels based on the self‐assembly and local mineralization of Ag+‐coordinated Fmoc‐amino acids are reported. Such biometallohydrogels have the advantages of localized delivery and sustained release, reduced drug dosage and toxicity yet improved bioavailability, prolonged drug effect, and tunable mechanical strength. Furthermore, they can directly interact with the cell walls and membrane, resulting in the detachment of the plasma membrane and leakage of the cytoplasm. This leads to cell death, triggering a significant antibacterial effect against both Gram‐negative (Escherichia coli) and Gram‐positive (Staphylococcus aureus) bacteria in cells and mice. This study paves the way for developing a multifunctional integration platform based on simple biomolecules coordinated self‐assembly toward a broad range of biomedical applications.

The transition of peptides and proteins from the solution phase into fibrillar structures is ageneral phenomenon encountered in functional and aberrant biology and is increasingly exploited in soft materials science.H owever,t he fundamental molecular events underpinning the early stages of their assembly and subsequent growth have remained challenging to elucidate.H ere,w es how that liquid-liquid phase separation into solute-rich and solute-poor phases is af undamental step leading to the nucleation of supramolecular nanofibrils from molecular building blocks,including peptides and even amphiphilic amino acids.T he solute-rich liquid droplets act as nucleation sites,a llowing the formation of thermodynamically favorable nanofibrils following Ostwalds step rule.T he transition from solution to liquid droplets is entropyd riven while the transition from liquid droplets to nanofibrils is mediated by enthalpic interactions and characterizedb ys tructural reorganization. These findings shed light on howt he nucleation barrier towardt he formation of solid phases can be lowered through ak inetic mechanism which proceeds through ametastable liquid phase.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Photothermal nanomedicine based on self‐assembly of biological components, with excellent biosafety and customized performance, is vital significance for precision cancer therapy. However, the programmable design of photothermal nanomedicine remains extremely challenging due to the vulnerability and variability of noncovalent interactions governing supramolecular self‐assembly. Herein, it is reported that amino acid encoding is a facile and potent means to design and construct supramolecular photothermal nanodrugs with controlled therapeutic activities. It is found that the amount and type of amino acid dominates the assembled nanostructures, structural stability, energy‐conversion pathway, and therapeutic mechanism of the resulting nanodrugs. Two optimized nanodrugs are endowed with robust structural integrity against disassembly along with high photothermal conversion efficiency, efficient cellular internalization, and enhanced tumor accumulation, which result in more efficient tumor ablation. This work demonstrates that design based on amino acid encoding offers an unprecedented opportunity for the construction of remarkable photoactive nanomedicines toward cancer diagnostics and therapeutics.