Near-Infrared Light-Activated Phototherapy by Gold Nanoclusters for Dispersing Biofilms.

A bacterial biofilm is strongly associated with chronic infections and is difficult to be eradicated, posing serious threats to public health. Development of effective therapeutic strategies to prevent and control hospital-acquired infections via eradication of bacteria shielded by biofilms is challenging. Herein, we developed deoxyribonuclease (DNase)-functionalized gold nanoclusters (AuNCs) (DNase-AuNCs), which are capable of killing Gram-positive and Gram-negative bacteria, especially dispersing the surrounding biofilms. The DNase can break down the extracellular polymeric substance matrix to expose the defenseless bacteria to photothermal therapy (PTT) and photodynamic therapy (PDT) by DNase-AuNCs under 808 nm laser irradiation. The combination of enzymolysis, PDT, and PTT can effectively remove biofilms with a dispersion rate of up to 80% and kill ∼90% of the shielded bacteria. DNase-AuNCs exhibit an outstanding therapeutic effect in treating bacterial biofilm-coated orthodontic devices (Invisalign aligners), suggesting their potential applications in medical devices.

Cell-Based Assays on Microfluidics for Drug Screening.

Microfluidics is an appealing platform for drug screening and discovery. Compared with the conventional drug screening methods based on Petri dishes and experimental animals, microfluidic devices have many advantages including miniaturized size, ease-to-use, high sensitivity, and high throughput. More importantly, bioassays on microfluidics can avoid ethical issues which can be a big obstacle hindering the performance of the experiments on animals or human being. Furthermore, three-dimensional (3D) microchips can recapitulate various biochemical and biophysical conditions in vivo and mimic the natural microenvironment of the tissues/organs, providing versatile in vitro models for biomedical applications. In this Perspective, we will focus on the cell-based microfluidic assays for drug screening. Meanwhile, we also propose potential solutions for the difficulties in this field and discuss the prospects of microfluidics-based technologies for drug screening.

Thermo-triggered Release of CRISPR-Cas9 System by Lipid-Encapsulated Gold Nanoparticles for Tumor Therapy.

CRISPR/Cas9 system is a powerful toolbox for gene editing. However, the low delivery efficiency is still a big hurdle impeding its applications. Herein, we report a strategy to deliver Cas9-sgPlk-1 plasmids (CP) by a multifunctional vehicle for tumor therapy. We condensed CPs on TAT peptide-modified Au nanoparticles (AuNPs/CP, ACP) via electrostatic interactions, and coated lipids (DOTAP, DOPE, cholesterol, PEG2000-DSPE) on the ACP to form lipid-encapsulated, AuNPs-condensed CP (LACP). LACP can enter tumor cells and release CP into the cytosol by laser-triggered thermo-effects of the AuNPs; the CP can enter nuclei by TAT guidance, enabling effective knock-outs of target gene (Plk-1) of tumor (melanoma) and inhibition of the tumor both in vitro and in vivo. This AuNPs-condensed, lipid-encapsulated, and laser-controlled delivery system provides a versatile method for high efficiency CRISPR/Cas9 delivery and targeted gene editing for treatment of a wide spectrum of diseases.