Gaocan Li

Preparation of organic mechanochromic fluorophores with simple structures and promising mechanochromic luminescence properties

Organic mechanochromic fluorescent materials have attracted increasing interest over the last few years. However, organic mechanochromic fluorophores reported so far usually have complicated structures and require multi-step synthesis. In this paper, a simple method to design and synthesize organic mechanochromic fluorophores with simple structures and promising mechanochromic luminescence properties is reported. Based on this method, a broad range of pyrene-based phosphonium materials with promising mechanochromic luminescence have been developed. Among all pyrene-based mechanochromic materials reported so far, tributyl(pyren-1-ylmethyl)phosphonium fluorophore 1·PF6 reported in this paper is the smallest pyrene-based mechanochromic fluorophore with the longest emission wavelength shift. The method reported in this study has shown great potential for the rapid construction of mechanochromic materials and opened a new avenue to develop novel mechanochromic materials.

Highly specific probe for dual-emissive mitochondrial imaging based on a photostable and aqueous-soluble phosphonium fluorophore

In recent years, fluorescent mitochondrial imaging has emerged as a powerful tool for monitoring the biological processes of mitochondria with high spatial and temporal resolution. However, conventional fluorescent reagents for mitochondrial imaging usually suffer from poor photostability and poor solubility in water as well as complex molecular structure and multi-step synthesis. Therefore, the development of an efficient method to construct specifically mitochondria-targeted molecules with superior photostability and aqueous solubility is in high demand for the study of mitochondrial functions. In this manuscript, a new type of aqueous-soluble fluorescent probe based on the perylene skeleton has been developed efficiently and exhibits high specificity to mitochondria with dual-emissive luminescence in living cells. To the best of our knowledge, this is the first report of a dual-emissive probe for specific mitochondrial imaging. Moreover, this perylene-based probe also exhibits superior photostability. The dual-emissive imaging, high specificity, and superior photostability as well as the efficient preparation make this perylene-based phosphonium fluorophore highly attractive as a fluorescent probe for mitochondrial imaging.

High contrast stimuli-responsive luminescence switching of pyrene-1-carboxylic esters triggered by a crystal-to-crystal transition

Unexpected high contrast mechanochromic, thermochromic and vaporchromic luminescence has been achieved through a simple introduction of an ester group to a pyrene skeleton and a series of stimuli-responsive materials based on pyrene-1-carboxylic esters were efficiently developed. The mechanistic investigation of stimuli-responsive luminescence indicates that the emission change might be ascribed to a reversible crystal-to-crystal transition. Furthermore, the electron-withdrawing effect of the ester groups to suppress the π–π interaction of the pyrene rings might be the key factor to trigger the promising stimuli-responsive luminescence.

Cation–anion interaction directed dual-mode switchable mechanochromic luminescence

In the past few years, organic mechanochromic materials have attracted more and more attention and a number of organic mechanochromic materials have been reported. However, only a single mode for switching of mechanochromic luminescence, either red-shift or blue-shift of the luminescence, can be observed for all the reported mechanochromic materials. Herein, based on a single tributyl(perylen-3-ylmethyl)phosphonium (TPMP) fluorophore, dramatic dual-mode switchable mechanochromic luminescence triggered by tunable cation–anion interactions has been reported for the first time. The trend of mechanochromic luminescence changes gradually from a red-shift to a blue-shift along with the strength order of the cation–anion interaction: Br− > BF4− > PF6− > NTf2−. A reversible transition of a crystalline state to an amorphous phase might be involved in the mechanochromic luminescence of TPMP·X (X = counteranion) with different counteranions.

Cation–anion interaction-directed formation of functional vesicles and their biological application for nucleus-specific imaging

A strategy for construction of counterion-induced vesicles in aqueous media has been described using imidazolium salts with multiple imidazolium moieties and alkyl carboxylate counteranions. The spontaneous formation of vesicles can be achieved by the simple selection of the counteranion to satisfy the requirement of the packing parameter for vesicle formation. Functional fluorescent vesicles can also be formed by the introduction of an aggregation-induced emission (AIE) fluorophore, tetraphenylethene (TPE), as the core of the imidazolium salt TPEI-C8, which also exhibits highly specific nucleus imaging in living cells. Considering the distinct AIE characteristic of TPEI-C8, the aggregation-induced strong fluorescence emission of TPEI-C8 in the cell nucleus may be the main reason for the specific fluorescence images of the cell nucleus. The strategy for the construction of functional vesicles reported in this study has shown great potential for the construction of other functional vesicles.

Micelles prepared from poly(N-isopropylacrylamide-co-tetraphenylethene acrylate)-b-poly [oligo(ethylene glycol) methacrylate] double hydrophilic block copolymer as hydrophilic drug carrier

Self-assembled micelles obtained from a double hydrophilic block copolymer (DHBC) based on poly(N-isopropylacrylamide) (PNIPAAm) are a facile and green strategy compared to the conventional solvent exchange method. However, hydrophobic drug encapsulation in micelles from PNIPAAm-based DHBC has relatively low drug loading (DL) and encapsulation efficiency (EE). Intermolecular and intramolecular hydrogen bondings of PNIPAAm chains are formed to exclude hydrophobic drugs. Nevertheless, hydrogen bonding can be used for hydrophilic drug delivery. Therefore, we report micelles prepared from a poly(N-isopropylacrylamide-co-tetraphenylethene acrylate)-b-poly[oligo(ethylene glycol) methacrylate] [P(NIPAAm-co-TPE)-b-POEGMA] double hydrophilic block copolymer as a hydrophilic drug (thymopentin, TP5) carrier. The FTIR results confirm hydrogen bond formation between PNIPAAm chain and TP5. Micelles are obtained by simply increasing the temperature above the critical micelle temperature (CMT). The self-assembly behaviour of polymeric micelles is investigated by DLS, TEM and aggregation-induced emission (AIE) phenomenon. Cytotoxicity results indicate that the micelles are biocompatible. The in vitro prolonged drug release (from 6 min to several hours) and in vivo immunity enhancement indicate that the micelles formed by P(NIPAAm-co-TPE)-b-POEGMA DHBC are promising candidates as hydrophilic drug carriers, where hydrogen bonding is formed between PNIPAAm and drug.

Redox-Responsive Biomimetic Polymeric Micelle for Simultaneous Anticancer Drug Delivery and Aggregation-Induced Emission Active Imaging

Intelligent polymeric micelles have been developed as potential nanoplatforms for efficient drug delivery and diagnosis. Herein, we successfully prepared redox-sensitive polymeric micelles combined aggregation-induced emission (AIE) imaging as an outstanding anticancer drug carrier system for simultaneous chemotherapy and bioimaging. The amphiphilic copolymer TPE-SS-PLAsp- b-PMPC could self-assemble into spherical micelles, and these biomimetic micelles exhibited great biocompatibility and remarkable ability in antiprotein adsorption, showing great potential for biomedical application. Anticancer drug doxorubicin (DOX) could be encapsulated during the self-assembly process, and these drug-loaded micelles showed intelligent drug release and improved antitumor efficacy due to the quick disassembly in response to high levels of glutathione (GSH) in the environment. Moreover, the intracellular DOX release could be traced through the fluorescent imaging of these AIE micelles. As expected, the in vivo antitumor study exhibited that these DOX-carried micelles showed better antitumor efficacy and less adverse effects than that of free DOX. These results strongly indicated that this smart biomimetic micelle system would be a prominent candidate for chemotherapy and bioimaging.

Redox and pH Dual-Responsive Polymeric Micelles with Aggregation-Induced Emission Feature for Cellular Imaging and Chemotherapy

Intelligent polymeric micelles for antitumor drug delivery and tumor bioimaging have drawn a broad attention because of their reduced systemic toxicity, enhanced efficacy of drugs, and potential application of tumor diagnosis. Herein, we developed a multifunctional polymeric micelle system based on a pH and redox dual-responsive mPEG-P(TPE- co-AEMA) copolymer for stimuli-triggered drug release and aggregation-induced emission (AIE) active imaging. These mPEG-P(TPE- co-AEMA)-based micelles showed excellent biocompatibility and emission property, exhibiting great potential application for cellular imaging. Furthermore, the antitumor drug doxorubicin (DOX) could be encapsulated during self-assembly process with high loading efficiency, and a DOX-loaded micelle system with a size of 68.2 nm and narrow size distribution could be obtained. DOX-loaded micelles demonstrated great tumor suppression ability in vitro, and the dual-responsive triggered intracellular drug release could be further traced. Moreover, DOX-loaded micelles could efficiently accumulate at the tumor site because of enhanced permeability and retention effect and long circulation of micelles. Compared with free DOX, DOX-loaded micelles exhibited better antitumor effect and significantly reduced adverse effects. Given the efficient accumulation targeting to tumor tissue, dual-responsive drug release, and excellent AIE property, this polymeric micelle would be a potential candidate for cancer therapy and diagnosis.