The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201904106.Bacterial infection is one of the top ten leading causes of death globally and the worst killer in low-income countries. The overuse of antibiotics leads to ever-increasing antibiotic resistance, posing a severe threat to human health. Recent advances in nanotechnology provide new opportunities to address the challenges in bacterial infection by killing germs without using antibiotics. Antibiotic-free antibacterial strategies enabled by advanced nanomaterials are presented. Nanomaterials are classified on the basis of their mode of action: nanomaterials with intrinsic or light-mediated bactericidal properties and others that serve as vehicles for the delivery of natural antibacterial compounds. Specific attention is given to antibacterial mechanisms and the structureperformance relationship. Practical antibacterial applications employing these antibiotic-free strategies are also introduced. Current challenges in this field and future perspectives are presented to stimulate new technologies and their translation to fight against bacterial infection.

Nature's creations with spiky topological features typically exhibit intriguing surface adhesive properties. From micrometer-sized pollen grains that can easily stick to hairy insects for pollination to nanoscale virus particles that are highly infectious toward host cells, multivalent interactions are formed taking advantage of rough surfaces. Herein, this nature-inspired concept is employed to develop novel drug delivery nanocarriers for antimicrobial applications. A facile new approach is developed to fabricate silica nanopollens (mesoporous silica nanospheres with rough surfaces), which show enhanced adhesion toward bacteria surfaces compared to their counterparts with smooth surfaces. Lysozyme, a natural antimicrobial enzyme, is loaded into silica nanopollens and shows sustained release behavior, potent antimicrobial activity, and long-term total bacterial inhibition up to 3 days toward Escherichia coli. The potent antibacterial activity of lysozyme-loaded silica nanopollens is further demonstrated ex vivo by using a small-intestine infection model. Our strategy provides a novel pathway in the rational design of nanocarriers for efficient drug delivery.

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A new type of monodispersed mesoporous silica nanoparticles with a core-cone structure (MSN-CC) has been synthesized. The large cone-shaped pores are formed by silica lamellae closely packed encircling a spherical core, showing a structure similar to the flower dahlia. MSN-CC has a large pore size of 45 nm and a high pore volume of 2.59 cm(3) g(-1). MSN-CC demonstrates a high loading capacity of large proteins and successfully delivers active β-galactosidase into cells, showing their potential as efficient nanocarriers for the cellular delivery of proteins with large molecular weights.

Iron oxide nanoparticles (IONPs) have emerging anti-cancer applications via polarizing tumor-associated macrophages from tumor-promoting phenotype (M2) to tumor-suppressing phenotype (M1). However, the underlying mechanism and structure-function relationship remain unclear. We report magnetite IONPs are more effective compared to hematite in M1 polarization and tumor suppression. Moreover, magnetite IONPs specifically rely on interferon regulatory factor 5 signaling pathway for M1 polarization and downregulate M2-assoicated arginase-1. This study provides new understandings and paves the way for designing advanced iron-based anti-cancer technologies.