Mutualistic Synthesis from Orthogonal Dynamic Covalent Reactions.

Mutualisms are interactions that benefit all species involved. It has been widely investigated in neighbouring subjects, such as biology, ecology, sociology, and economics. However, such a reciprocal relationship in synthetic chemical systems has rarely been studied. Here, we demonstrate a mutualistic synthesis where byproducts from two orthogonal chemical reactions aid each other's production. Disulfide exchange and hydrazone exchange were chosen to generate two dynamic combinatorial libraries. A minor tetrameric macrocycle from the active disulfide library was quantitatively amplified in the presence of the hydrazone library. This incorporation also turned on the previously inert hydrazone reaction, producing a linear species that formed a "handcuffs" catenane with the disulfide tetramer. These findings not only lend robust support to the hypothesis of "RNA-peptide coevolution" for the origin of life but also broaden the scope of synthetic chemistry, highlighting the untapped potential of minor products from different reactions. Additionally, the co-self-assembly of these mutualistic entities to form supramolecular structures opens new avenues for future development of composite nanosystems with synergistic properties.

Protocol for preparing dynamic covalent macrocycles for co-delivering genes and drugs to cancer cell lines.

Combination therapy using effective drug molecules and functional genes such as small interfering RNA (siRNA) has been suggested as a powerful strategy against multiple drug resistance. Here, we present a protocol for preparing a delivery system by developing dynamic covalent macrocycles using a dithiol monomer to co-deliver doxorubicin and siRNA. We describe steps for preparing the dithiol monomer, followed by co-delivery to form nanoparticles. We then detail procedures for cell uptake and assessing enhanced anti-cancer efficacy in vitro. For complete details on the use and execution of this protocol, please refer to Lyu et al.1.

Using host-guest interactions at the interface of quantum dots to load drug molecules for biocompatible, safe, and effective chemo-photodynamic therapy against cancer.

Combining photodynamic therapy (PDT) and chemotherapy (CHT) by loading an anti-cancer drug and a photosensitizer (PS) into the same delivery nanosystem has been proposed as an effective approach to achieve synergistic effects for a safe cancer treatment. However, exploring an ideal delivery nanosystem has been challenging, because the noncovalent interactions must be maintained between the multiple components to produce a stable yet responsive nanostructure that takes into account the encapsulation of drug molecules. We addressed this issue by engineering the interfacial interaction between Ag2S quantum dots (QDs) using a pillararene derivative to direct the co-self-assembly of the entire system. The high surface area-to-volume ratio of the Ag2S QDs provided ample hydrophobic space to accommodate the anti-drug molecule doxrubicine. Moreover, Ag2S QDs served as PSs triggered by 808 nm near-infrared (NIR) light and also as carriers for high-efficiency delivery of drug molecules to the tumor site. Drug release experiments showed smart drug release under the acidic microenvironments (pH 5.5) in tumor cells. Additionally, the Ag2S QDs demonstrated outstanding PDT ability under NIR light, as confirmed by extracellular and intracellular reactive oxygen species generation. Significant treatment efficacy of the chemo-photodynamic synergistic therapy for cancer using the co-delivery system was demonstrated via in vitro and in vivo studies. These findings suggest that our system offers intelligent control of CHT and PDT, which will provide a promising strategy for constructing hybrid systems with synergistic effects for advanced applications in biomedicine, catalysis, and optoelectronics.

A dual ammonia-responsive sponge sensor: preparation, transition mechanism and sensitivity.

PDMS-PU (polydimethylsiloxane-polyurethane) sponge decorated with In(OH)3 (indium hydroxide) and BCP (bromocresol purple) particles is shown to be a room-temperature ammonia sensor with high sensitivity and excellent reproducibility; it can accomplish real-time detection and monitoring of ammonia in the surrounding environment. The superhydrophobic and yellowish In(OH)3-BCP-TiO2-based ammonia-responsive (IBT-AR) sponge changes to a purple superhydrophilic one when exposed to ammonia. Notably, after reacting with ammonia, the sponge can recover its original wettability and color after heating in air. The wettability, color and absorption signal of IBT-AR sponge have been measured for sensing ammonia using the water contact angle, macroscopic observation and UV-vis absorption spectrometry, respectively. The minimum ammonia concentrations that can be detected by the sponge wettability, color and absorption signal are 0.5%, 1.4 ppm and 50 ppb, respectively. This kind of sponge with smart wettability and color is a promising new ammonia detector.