New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus, whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria.
Multiplexed
detection of extracellular vesicle (EV)-derived microRNAs
(miRNAs) plays a critical role in facilitating disease diagnosis and
prognosis evaluation. Herein, we developed a highly specific nucleic
acid detection platform for simultaneous quantification of several
EV-derived miRNAs in constant temperature by integrating the advantages
of a clustered regularly interspaced short palindromic repeats/CRISPR
associated nucleases (CRISPR/Cas) system and rolling circular amplification
(RCA) techniques. Particularly, the proposed approach demonstrated
single-base resolution attributed to the dual-specific recognition
from both padlock probe-mediated ligation and protospacer adjacent
motif (PAM)-triggered cleavage. The high consistency between the proposed
approach RCA-assisted CRISPR/Cas9 cleavage (RACE) and reverse transcription
quantitative polymerase chain reaction (RT-qPCR) in detecting EV-derived
miRNAs’ abundance from both cultured cancer cells and clinical
lung cancer patients validated its robustness, revealing its potentials
in the screening, diagnosis, and prognosis of various diseases. In
summary, RACE is a powerful tool for multiplexed, specific detection
of nucleic acids in point-of-care diagnostics and field-deployable
analysis.
Bacterial outer membrane vesicle (OMV) is a kind of spherical lipid bilayer nanostructure naturally secreted by bacteria, which has diverse functions such as intracellular and extracellular communication, horizontal gene transfer, transfer of contents to host cells, and eliciting an immune response in host cells. In this review, several methods including ultracentrifugation and precipitation for isolating OMVs were summarized. The latest progresses of OMVs in biomedical fields, especially in vaccine development, cancer treatment, infection control, and bioimaging and detection were also summarized in this review. We highlighted the importance of genetic engineering for the safe and effective application and in facilitating the rapid development of OMVs. Finally, we discussed the bottleneck problems about OMVs in preparation and application at present and put forward our own suggestions about them. Some perspectives of OMVs in biomedical field were also provided.
Immunological adjuvants are essential for successful cancer vaccination. However, traditional adjuvants have some limitations, such as lack of controllability and induction of systemic toxicity, which restrict their broad application. Here, we present a light-activable immunological adjuvant (LIA), which is composed of a hypoxia-responsive amphiphilic dendrimer nanoparticle loaded with chlorin e6. Under irradiation with near-infrared light, the LIA not only induces tumour cell lysis and tumour antigen release, but also promotes the structural transformation of 2-nitroimidazole containing dendrimer to 2-aminoimidazole containing dendrimer which can activate dendritic cells via the Toll-like receptor 7-mediated signaling pathway. The LIA efficiently inhibits both primary and abscopal tumour growth and induces strong antigen-specific immune memory effect to prevent tumour metastasis and recurrence in vivo. Furthermore, LIA localizes the immunological adjuvant effect at the tumour site. We demonstrate this light-activable immunological adjuvant offers a safe and potent platform for in situ cancer vaccination.
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