Pre-targeted Imaging of Protease Activity through In Situ Assembly of Nanoparticles

The pre-targeted imaging of enzyme activity has not been reported, likely owing to the lack of a mechanism to retain the injected substrate in the first step for subsequent labeling. Herein, we report the use of two bioorthogonal reactions—the condensation reaction of aromatic nitriles and aminothiols and the inverse-electron demand Diels–Alder reaction between tetrazine and trans-cyclooctene (TCO)—to develop a novel strategy for pre-targeted imaging of the activity of proteases. The substrate probe ( TCO-C-SNAT4 ) can be selectively activated by an enzyme target (e.g. caspase-3/7), which triggers macrocyclization and subsequent in situ self-assembly into nanoaggregates retained at the target site. The tetrazine-imaging tag conjugate labels TCO in the nanoaggregates to generate selective signal retention for imaging in vitro, in cells, and in mice. Owing to the decoupling of enzyme activation and imaging tag immobilization, TCO-C-SNAT4 can be repeatedly injected to generate and accumulate more TCO-nanoaggregates for click labeling.     

Microenvironment‐Induced In Situ Self‐Assembly of Polymer–Peptide Conjugates That Attack Solid Tumors Deeply

In cancer treatment, the unsatisfactory solid‐tumor penetration of nanomaterials limits their therapeutic efficacy. We employed an in vivo self‐assembly strategy and designed polymer–peptide conjugates (PPCs) that underwent an acid‐induced hydrophobicity increase with a narrow pH‐response range (from 7.4 to 6.5). In situ self‐assembly in the tumor microenvironment at appropriate molecular concentrations (around the IC₅₀ values of PPCs) enabled drug delivery deeper into the tumor. A cytotoxic peptide KLAK, decorated with the pH‐sensitive moiety cis‐aconitic anhydride (CAA), and a cell‐penetrating peptide TAT were conjugated onto poly(β‐thioester) backbones to produce PT‐K‐CAA, which can penetrate deeply into solid tumors owing to its small size as a single chain. During penetration in vivo, CAA responds to the weak acid, leading to the self‐assembly of PPCs and the recovery of therapeutic activity. Therefore, a deep‐penetration ability for enhanced cancer therapy is provided by this in vivo assembly strategy.     

An All‐Inorganic Colloidal Nanocrystal Flexible Polarizer

Inorganic single crystals with anisotropic structures usually suffer from high brittleness and stiffness. Flexible polymers are used to replace inorganic crystals, but the hot‐stretching‐induced orientation process is tedious, and oriented molecular chains tend to revert to random coils during aging. To overcome these obstacles and using the similarities between sub‐1 nm nanowires (NWs) and linear polymers, we successfully fabricated anisotropic, transparent, flexible, and stable (ATFS) NW films with great potential for optical applications through a wet‐spinning method. The NW films show birefringence, and their birefractive index is higher than that of many polymers. They also showed polarized absorption of UV light and anisotropic scattering of visible light. The integrated films composed of NWs and quantum dots showed good fluorescence polarization. The tedious synthesis of quantum rods and fabrication of oriented polymer films can thus be avoided.     

Kinetic Control of Aggregation Shape in Micellar Self‐Assembly

The first steps towards top‐down morphology control in micellar self‐assembly are introduced. Kinetically stable micelles are formed from block copolymers (BCPs) using continuous flow techniques by turbulent mixing of water with a THF solution of polymers. In this way, particle shape and size can be altered from spheres to ellipsoids solely via tuning of mixing parameters from a single BCP.     

Catalytically Active Peptide–Gold Nanoparticle Conjugates: Prospecting for Artificial Enzymes

The self-assembly of peptides onto the surface of gold nanoparticles has emerged as a promising strategy towards the creation of artificial enzymes. The resulting high local peptide density surrounding the nanoparticle leads to cooperative and synergistic effects, which result in rate accelerations and distinct catalytic properties compared to the unconjugated peptide. This Minireview summarizes contributions to and progress made in the field of catalytically active peptide–gold nanoparticle conjugates. The origin of distinct properties, as well as potential applications, are also discussed.     

Dual-Phase Thermally Activated Delayed Fluorescence Luminogens: A Material for Time-Resolved Imaging Independent of Probe Pretreatment and Probe Concentration

Developing luminescent probes with long lifetime and high emission efficiency is essential for time-resolved imaging. However, the practical applications usually suffer from emission quenching of traditional luminogens in aggregated states, or from weak emission of aggregation-induced emission type luminogens in monomeric states. Herein, we overcome this dilemma by a rigid-and-flexible alternation design in donor–acceptor–donor skeletons, to achieve a thermally activated delayed fluorescence luminogen with high emission efficiency both in the monomeric state (quantum yield up to 35.3 %) and in the aggregated state (quantum yield up to 30.8 %). Such a dual-phase strong and long-lived emission allows a time-resolved luminescence imaging, with an efficiency independent of probe pretreatment and probe concentration. The findings open opportunities for developing luminescent probes with a usage in larger temporal and spatial scales.