The Marriage of Aggregation-Induced Emission with Polymer Science.

Aggregation-induced emission (AIE) is a novel photophysical phenomenon coined in 2001 by our group and describes the enhanced light emission of some luminogens in the aggregate or solid state. The combination of AIE research and polymer science is a smart approach to produce functional luminescent materials with mechanical strength and excellent processability for real-world applications. In this feature article, recent progress in AIE polymeric systems, including chemical synthesis and physical blending strategies, is summarized. Through chemical synthesis, various AIE-active polymers, such as covalently bonded polymers, supramolecular polymers, and nonconjugated luminescent polymers, can be obtained. Serving as environmentally sensitive probes, AIE luminogens can also be physically doped into polymers to generate interesting systems. Finally, outlooks and perspectives on the future direction of AIE polymeric systems are discussed.

Spatiotemporally sequential delivery of biomimetic liposomes potentiates glioma chemotherapy.

As one of the most challenging cancers, glioma still lacks efficient therapeutic treatment in clinics. The dilemmas of nanodrug-based therapies for glioma are due not only the limited permeability of the blood-brain barrier (BBB) but also the deficiency of targeting tumor lesions. Thus, spatiotemporally sequential delivery of therapeutics from BBB-crossing to glioma accumulation is considered a strategy to obtain better outcomes. Here, we developed a biomimetic chemotherapy nanodrug composed of the hybrid membrane envelope of U87 cell membranes and RAW264.7 cell membranes, and the core of paclitaxel (PTX)-loaded liposome (PTX@C-MMCL). In the research, PTX@C-MMCL showed superior ability to cross the BBB via RAW264.7 cell membranes and accurate targeting to the brain tumor lesions relying on the homotypic targeting capacity of U87 cell membranes. Furthermore, PTX@C-MMCL can maintain a prolonged circulation in vivo. Importantly, PTX@C-MMCL effectively inhibited the development of glioma. Conclusively, our biomimetic nanodrug holds great potential for brain tumor targeting therapy.

Multi-Stimuli-Responsive and Cell Membrane Camouflaged Aggregation-Induced Emission Nanogels for Precise Chemo-photothermal Synergistic Therapy of Tumors.

Targeted and controllable drug release at lesion sites with the aid of visual navigation in real-time is of great significance for precise theranostics of cancers. Benefiting from the marvelous features (e.g., bright emission and phototheranostic effects in aggregates) of aggregation-induced emission (AIE) materials, constructing AIE-based multifunctional nanocarriers that act as all-arounders to integrate multimodalities for precise theranostics is highly desirable. Here, an intelligent nanoplatform (P-TN-Dox@CM) with homologous targeting, controllable drug release, and in vivo dual-modal imaging for precise chemo-photothermal synergistic therapy is proposed. AIE photothermic agent (TN) and anticancer drug (Dox) are encapsulated in thermo-/pH-responsive nanogels (PNA), and the tumor cell membranes are camouflaged onto the surface of nanogels. Active targeting can be realized through homologous effects derived from source tumor cell membranes, which advantageously elevates the specific drug delivery to tumor sites. After being engulfed into tumor cells, the nanogels exhibit a burst drug release at low pH. The near-infrared (NIR) photoinduced local hyperthermia can activate severe cytotoxicity and further accelerate drug release, thus generating enhanced synergistic chemo-photothermal therapy to thoroughly eradicate tumors. Moreover, P-TN-Dox@CM nanogels could achieve NIR-fluorescence/photothermal dual-modal imaging to monitor the dynamic distribution of therapeutics in real-time. This work highlights the great potential of smart P-TN-Dox@CM nanogels as a versatile nanoplatform to integrate multimodalities for precise chemo-photothermal synergistic therapy in combating cancers.

Pursuing Phase Transitions of a Concentrated Polymer Solution by In Situ Fluorescence Measurements Based On Aggregation-Induced Emission.

Concentration-dependent phase transitions in concentrated solutions have remained speculation due to the serious impediment of macromolecule dynamics by intensive topological entanglement or intermolecular interaction as well as the absence of powerful tool for detecting changes in chain or segment movement. Herein, taking a general polymer, namely, poly(vinyl alcohol) (PVA), as an example, a water-soluble fluorescent molecule with aggregation-induced emission (AIE) is introduced into the PVA solutions as a chain dynamics indicator to investigate phase transitions at high concentrations through in situ monitoring of the solvent evaporation process. Two turning points of fluorescent intensity are observed for the first time at mean concentrations of ∼25% and ∼45%, corresponding to the gelation and amorphous-to-crystalline transitions, respectively. Our work offers a fundamental insight into the physical nature of concentrate-dependent nonequilibrium transitions and develops a reliable and sensitive approach based on the AIE phenomenon for following high-concentration-triggered property changes of a polymer solution.

Cyclam-Modified Polyethyleneimine for Simultaneous TGFß siRNA Delivery and CXCR4 Inhibition for the Treatment of CCl4-Induced Liver Fibrosis.

BACKGROUND: Liver fibrosis is a chronic liver disease with excessive production of extracellular matrix proteins, leading to cirrhosis, hepatocellular carcinoma, and death. PURPOSE: This study aimed at the development of a novel derivative of polyethyleneimine (PEI) that can effectively deliver transforming growth factor ß (TGFß) siRNA and inhibit chemokine receptor 4 (CXCR4) for TGFß silencing and CXCR4 Inhibition, respectively, to treat CCl4-induced liver fibrosis in a mouse model. METHODS: Cyclam-modified PEI (PEI-Cyclam) was synthesized by incorporating cyclam moiety into PEI by nucleophilic substitution reaction. Gel electrophoresis confirmed the PEI-Cyclam polyplex formation and stability against RNAase and serum degradation. Transmission electron microscopy and zeta sizer were employed for the morphology, particle size, and zeta potential, respectively. The gene silencing and CXCR4 targeting abilities of PEI-Cyclam polyplex were evaluated by luciferase and CXCR4 redistribution assays, respectively. The histological and immunohistochemical staining determined the anti-fibrotic activity of PEI-Cyclam polyplex. The TGFß silencing of PEI-Cyclam polyplex was authenticated by Western blotting. RESULTS: The 1H NMR of PEI-Cyclam exhibited successful incorporation of cyclam content onto PEI. The PEI-Cyclam polyplex displayed spherical morphology, positive surface charge, and stability against RNAse and serum degradation. Cyclam modification decreased the cytotoxicity and demonstrated CXCR4 antagonistic and luciferase gene silencing efficiency. PEI-Cyclam/siTGFß polyplexes decreased inflammation, collagen deposition, apoptosis, and cell proliferation, thus ameliorating liver fibrosis. Also, PEI-Cyclam/siTGFß polyplex significantly downregulated α-smooth muscle actin, TGFß, and collagen type III. CONCLUSION: Our findings validate the feasibility of using PEI-Cyclam as a siRNA delivery vector for simultaneous TGFß siRNA delivery and CXCR4 inhibition for the combined anti-fibrotic effects in a setting of CCl4-induced liver fibrosis.

Recent New Methodologies for Acetylenic Polymers with Advanced Functionalities.

Polymers synthesized from acetylenic monomers often possess electronically unsaturated fused rings and thus show versatile optoelectronic properties and advanced functionalities. To expand the family of acetylenic polymers, development of new catalyst systems and synthetic routes is critically important. We summarize herein recent research progress on development of new methodologies towards functional polymers using alkyne building blocks since 2014. The polymerizations are categorized by the number of monomer components, namely homopolymerizations, two-component polymerizations, and multicomponent polymerizations. The properties and applications of acetylenic polymers, such as aggregation-induced emission, fluorescent photopatterning, light refraction, chemosensing, mechanochromism, chain helicity, etc., are also discussed.