We first officially propose the brand-new concept of “biosafety materials”, which utilizes materials science to solve biosafety problems.

serious infections including tuberculosis, endocarditis, osteomyelitis, necrotizing pneumonia, and sepsis. [1] Treatment often requires long-term and intensive antibiotics administration; however, treatment failure and relapse are unfortunately common. [2] As we currently understand it, the major reasons for the failure of clinical therapy to eradicate intracellular bacteria include: i) poor cellular membrane penetration, suboptimal intracellular accumulation, and short retention of antibiotics; [3] ii) diminished antibacterial activity of antibiotics because of the harsh acidic and hydrolytic environment within phagolysosomes; [4] iii) intracellular bacteria being in a dormant state and tolerance of otherwise lethal concentration of antibiotics; [5] and iv) bacteria escape from phagolysosomes and hide in privileged intracellular compartments that evade the bactericidal actions of antibiotics. [6] At later timepoints, potentially after the cessation of therapy, the bacteria may then proliferate resulting in the apoptosis and autophagy of the cells. The evasive bacteria re-enter the circulation or re-infect local tissues. [7] As such, the infected cells have been likened to "Trojan horses" that protect bacteria with later dissemination of the infection into deeper tissues. [8] Drug delivery systems (DDSs) have shown increasing potential for the treatment of intracellular bacterial infection. [9] The Intracellular bacteria in latent or dormant states tolerate high-dose antibiotics. Fighting against these opportunistic bacteria has been a long-standing challenge. Herein, the design of a cascade-targeting drug delivery system (DDS) that can sequentially target macrophages and intracellular bacteria, exhibiting on-site drug delivery, is reported. The DDS is fabricated by encapsulating rifampicin (Rif ) into mannose-decorated poly(α-N-acryloylphenylalanine)-block-poly(β-N-acryloyl-d-aminoalanine) nanoparticles, denoted as Rif@FAM NPs. The mannose units on Rif@FAM NPs guide the initial macrophage-specific uptake and intracellular accumulation. After the uptake, the detachment of mannose in acidic phagolysosome via Schiff base cleavage exposes the d-aminoalanine moieties, which subsequently steer the NPs to escape from lysosomes and target intracellular bacteria through peptidoglycan-specific binding, as evidenced by the in situ/ex situ co-localization using confocal, flow cytometry, and transmission electron microscopy. Through the on-site Rif delivery, Rif@FAM NPs show superior in vitro and in vivo elimination efficiency than the control groups of free Rif or the DDSs lacking the macrophages-or bacteria-targeting moieties. Furthermore, Rif@FAM NPs remodel the innate immune response of the infected macrophages by upregulating M1/M2 polarization, resulting in a reinforced antibacterial capacity. Therefore, this biocompatible DDS enabling macrophages and bacteria targeting in a cascade manner provides a new outlook for the therapy of intracellular pathogen infection.

The limited drug penetration and robust bacteria‐mediated drug inactivation in pancreatic cancer result in the failure of chemotherapy. To fight against these issues, a dual‐cascade responsive nanoparticle (sNP@G/IR) that can sequentially trigger deep penetration, killing of intratumor bacteria, and controlled release of chemo‐drug, is reported. sNP@G/IR consists of a hyaluronic acid (HA) shell and glutathione (GSH)‐responsive polymer‐core (NP@G/IR), that encapsulates gemcitabine (Gem) and photothermal agent (IR1048). The polymer core, as an antibiotic alternative, is tailored to exert optimal antibacterial activity and selectivity. sNP@G/IR actively homes in on the tumor due to the CD44 targeting of the HA shell, which is subsequently degraded by the hyaluronidase in the extracellular matrix. The resultant NP@G/IR in decreased size and reversed charge facilitates deep tumor penetration. After cellular endocytosis, the exposed guanidine on NP@G/IR kills intracellular bacteria through disrupting cell membranes. Intracellular GSH further triggers the controlled release of the cargo. Thus, the protected Gem eventually induces cell apoptosis. Under laser irradiation, the hyperthermia of IR1048 helps further elimination of tumors and bacteria. Moreover, sNP@G/IR activates immune response, thereby reinforcing anticancer capacity. Therefore, this dual‐cascade responsive sNP@G/IR eliminates tumor‐resident intracellular bacteria and augments drug delivery efficacy, providing a new avenue for improving cancer therapy.

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Antimicrobial modification of poly­(ethylene terephthalate) (PET) is effective in preventing the adhesion and growth of microorganisms on its surface. However, few methods are available to modify PET directly at its backbone to impart the antimicrobial effect. Herein, menthoxytriazine-modified PET (PMETM) based on the stereochemical antimicrobial strategy was reported. This novel PET was prepared by inserting menthoxytriazine into the PET backbone. The antibacterial adhesion test and the antifungal landing test were employed to confirm the antiadhesion ability of PMETM. PMETM could effectively inhibit the adhesion of bacteria, with inhibition ratios of 99.9 and 99.7% against Escherichia coli (Gram-negative) and Bacillus subtilis (Gram-positive), respectively. In addition, PMETM exhibited excellent resistance to Aspergillus niger (fungal) contamination for more than 30 days. Cytotoxicity assays indicated that PMETM was a noncytotoxic material. These results suggested that the insertion of menthoxytriazine in the PET backbone was a promising strategy to confer antimicrobial properties to PET.