Antibacterial materials that prevent bacterial infections and mitigate bacterial virulence have attracted great scientific interests. In recent decades, the bactericidal polymers have been presented as promising candidates to combat bacterial pathogens, mainly based on the construction of bactericidal cationic polymers, functionalization with biocidal agents, and formation of bacterial-repelling layers. However, these established strategies have inherent disadvantages because they often overlook important features such as their biocompatibility and biosafety, especially for biomedical applications. In recent years, many efforts have been made focusing on the development of multifunctional antibacterial materials to meet the elaborate requirements for medical devices and public hygiene products. Herein the recent advances in developing multifunctional materials for their antibacterial activities together with other functions including "kill-and-release" capability, hemocompatibility, cell proliferation promoting properties, and coagulation promoting ability for wound dressing are highlighted. In addition, the outlooks on the remaining challenges that should be addressed in the field of multifunctional antibacterial materials are also described.

Biomedical device-associated infection (BAI) is a great challenge in modern clinical medicine. Therefore, developing efficient antibacterial materials is significantly important and meaningful for the improvement of medical treatment and people’s health. In the present work, we developed a strategy of surface functionalization for multifunctional antibacterial applications. A functionalized polyurethane (PU, a widely used biomedical material for hernia repairing) surface (PU-Au-PEG) with inherent antifouling and photothermal bactericidal properties was readily prepared based on a near-infrared (NIR)-responsive organic/inorganic hybrid coating which consists of gold nanorods (Au NRs) and polyethylene glycol (PEG). The PU-Au-PEG showed a high efficiency to resist adhesion of bacteria and exhibited effective photothermal bactericidal properties under 808 nm NIR irradiation, especially against multidrug-resistant bacteria. Furthermore, the PU-Au-PEG could inhibit biofilm formation long term. The biocompatibility of PU-Au-PEG was also proved by cytotoxicity and hemolysis tests. The in vivo photothermal antibacterial properties were first verified by a subcutaneous implantation animal model. Then, the anti-infection performance in a clinical scenario was studied with an infected hernia model. The results of animal experiment studies demonstrated excellent in vivo anti-infection performances of PU-Au-PEG. The present work provides a facile and promising approach to develop multifunctional biomedical devices.

Cationic agents, such as ionic liquids (ILs)-based species, have broad-spectrum antibacterial activities. However, the antibacterial mechanisms lack systematic and molecular-level research, especially for Gram-negative bacteria, which have highly organized membrane structures. Here, we designed a series of flexible fluorescent diketopyrrolopyrrole-based ionic liquid derivatives (ILDs) with various molecular sizes (1.95−4.2 nm). The structure−antibacterial activity relationships of the ILDs against Escherichia coli (E. coli) were systematically studied thorough antibacterial tests, fluorescent tracing, morphology analysis, molecular biology, and molecular dynamics (MD) simulations. ILD-6, with a relatively small molecular size, could penetrate through the bacterial membrane, leading to membrane thinning and intracellular activities. ILD-6 showed fast and efficient antimicrobial activity. With the increase of molecular sizes, the corresponding ILDs were proven to intercalate into the bacterial membrane, leading to the destabilization of the lipid bilayer and further contributing to the antimicrobial activities. Moreover, the antibacterial activity of ILD-8 was limited, where the size was not large enough to introduce significant membrane disorder. Relative antibacterial experiments using another common Gram-negative bacteria, Pseudomonas aeruginosa (PAO1), further confirmed the proposed structure-antibacterial activity relationships of ILDs. More impressively, both ILD-6 and ILD-12 displayed significant in vivo therapeutic effects on the PAO1-infected rat model, while ILD-8 performed poorly, which confirmed the antibacterial mechanism of ILDs and proved their potentials for future application. This work clarifies the interactions between molecular sizes of ionic liquid-based species and Gram-negative bacteria and will provide useful guidance for the rational design of high-performance antibacterial agents.

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging-guided therapy of cancer. In this work, a near-infrared (NIR)-triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two-armed ethanolamine-modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD-PGEA) has been successfully fabricated for multimodal imaging-guided triple-combination treatment of cancer. A hierarchical hetero-structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X-ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl-rich CD-PGEA/pDNA complexes, realizing the co-delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR-triggered release of DOX through the facilitated detachment of CD-PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging-guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.

Nucleic acid (NA)-based therapy is proposed to address serious diseases such as cardiovascular diseases (CVDs). Powerful NA delivery vehicles are essential for effective gene therapy. Herein, a novel type of delivery vehicle, an unlockable core-shell nanocomplex (Hep@PGEA) with self-accelerating NA release, is structurally designed. Hep@PGEA is composed of disulfide-bridged heparin nanoparticle (HepNP) core and low-toxicity PGEA cationic shell. In comparison with NA, heparin, a negatively charged polysaccharide macromolecule, exhibits stronger interactions with cationic species. Upon the breakdown of redox-responsive HepNP cores, unlocked heparin would interact with the outer cationic shells and replace the condensed NA to facilitate NA release. Such unique Hep@PGEA is successfully explored for effective miRNA-pDNA staged gene therapy of myocardial infarction (MI), one of the most serious CVDs. With the progression of MI, glutathione amounts in heart tissues increase. MiR-499 (for the inhibition of cardiomyocyte apoptosis) and plasmid encoding vascular endothelial growth factor (for the promotion of angiogenesis) are sequentially delivered for systemic treatment of MI. Such treatment produces impressive results in restoring heart function and suppressing cardiac hypertrophy. Due to the wide existence of redox agents in cells, the proposed unlockable delivery nanovehicle and staged therapy strategy can provide new methods to effectively treat different serious diseases.