A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing. These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre protein and Cas9:sgRNA complexed with bioreducible lipids into cultured human cells enables gene recombination and genome editing with efficiencies greater than 70%. In addition, we demonstrate that these lipids are effective for functional protein delivery into mouse brain for gene recombination in vivo. Therefore, the integration of this bioreducible lipid platform with protein engineering has the potential to advance the therapeutic relevance of protein-based genome editing.

New fluorescent sensors have been developed, utilizing the aggregation-induced emission (AIE) attribute of silole and tetraphenylethene luminogens. In this feature article, we briefly summarize recent progress in the development of AIE-based bio/chemosensors for assays of nuclease and AChE activities, screening of inhibitors, and detection of various analytes including charged biopolymers, ionic species, volatile and explosive organic compounds.

A novel approach towards the construction of multicomponent two-dimensional (2-D) and threedimensional (3-D) metallosupramolecules is reported. Simply by mixing carboxylate and pyridyl ligands with cis-Pt(PEt 3 ) 2 (OTf) 2 in a proper ratio, coordination-driven self-assembly occurs, allowing for selective generation of discrete multicomponent structures via charge separation on the metal centers. Using this method, a variety of 2-D rectangles and 3-D prisms were prepared under mild conditions. Moreover, multicomponent self-assembly can also be achieved by supramolecule-to-supramolecule transformations. The products were characterized by 31 P and 1 H multinuclear NMR spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and pulsed-field-gradient spin echo (PGSE) NMR techniques together with computational simulations.

Herein we report a convenient chemical approach to reversibly modulate protein (RNase A) function and develop a protein that is responsive to reactive oxygen species (ROS) for targeted cancer therapy. The conjugation of RNase A with 4-nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyl carbonate (NBC) blocks protein lysine and temporarily deactivates the protein. However, the treatment of RNase A-NBC with hydrogen peroxide (one major intracellular ROS) efficiently cleaves the NBC conjugation and restores the RNase A activity. Thus, RNase A-NBC can be reactivated inside tumor cells by high levels of intracellular ROS, thereby restoring the cytotoxicity of RNase A for cancer therapy. Due to higher ROS levels inside tumor cells compared to healthy cells, and the resulting different levels of RNase A-NBC reactivation, RNase A-NBC shows a significant specific cytotoxicity against tumor cells.