Morphological Transformation and In Situ Polymerization of Caspase-3 Responsive Diacetylene-Containing Lipidated Peptide Amphiphile for Self-Amplified Cooperative Antitumor Therapy.

In order to artificially regulate cell behaviors, intracellular polymerization as an emerging chemical technique has attracted much attention. Yet, it is still a challenge to achieve effective intracellular polymerization to conquer tumors in the complex cellular environment. Herein, this work develops a tumor-targeting and caspase-3 responsive nanoparticle composed of a diacetylene-containing lipidated peptide amphiphile and mitochondria-targeting photosensitizer (C3), which undergoes nanoparticle-to-nanofiber transformation and efficient in situ polymerization triggered by photodynamic treatment and activation of caspase-3. The locational nanofibers on the mitochondria membranes lead to mitochondrial reactive oxygen species (mtROS) burst and self-amplified circulation, offering persistent high oxidative stress to induce cell apoptosis. This study provides a strategy for greatly enhanced antitumor therapeutic efficacy through mtROS burst and self-amplified circulation induced by intracellular transformation and in situ polymerization.

Self-Adhesive Hyaluronic Acid/Antimicrobial Peptide Composite Hydrogel with Antioxidant Capability and Photothermal Activity for Infected Wound Healing.

Bacterial infection can delay wound healing, causing wounds to deteriorate and even threaten the patient's life. Recently, although many composite hydrogels as wound dressing have been developed, it is still highly desired to construct photothermal hydrogels with antimicrobial and antioxidant properties to accelerate the infected wound healing. In this work, a hyaluronic acid (HA)-based composite hydrogel consisting of a dopamine-substituted antimicrobial peptide (DAP) and Iron (III) ions is developed, which exhibits photothermal-assisted promotion and acceleration of healing process of bacteria-infected wounds. DAP, serving as both antimicrobial agent and ROS-scavenger, forms Schiff's base bonds with aldehyde hyaluronic acid (AHA) and iron-catechol coordination bonds to reinforce the composite hydrogel. The presence of Fe3+ can also promote covalent polymerization of dopamine, which endows the hydrogel with photothermal capacity. The in vitro and in vivo experiments prove that the composite hydrogel can effectively accelerate the infected wound healing process, including antibacterial, accelerated collagen deposition, and re-epithelization. This study suggests that the multifunctional composite hydrogel possesses remarkable potential for bacteria-infected wound healing by combining inherent antimicrobial activity, antioxidant capability, and photothermal effect.

An N-linked disalicylaldehyde together with its caesium ion and dichloromethane sensing performances: 'dual key & lock' LMCT-enhanced fluorescence strategy.

The development of inexpensive, selective and rapid-response chemosensors for detecting Cs+ in waste water is highly desirable in the nuclear power industry. Here we demonstrate an efficient Cs+ optical sensor based on the N-linked disalicylaldehyde H2Qj with excited state intramolecular proton transfer (ESIPT), and it will transform into the ligand-to-metal charge transfer (LMCT) process in the presence of Cs+, resulting in dramatically enhanced fluorescence together with a distinct change of color from light-green to green-yellow. Simultaneously, it is found that CH2Cl2 can serve as the quencher of LMCT-enhanced fluorescence, thus enabling selective CH2Cl2 detection in a turn-off fluorescence approach. Further detailed studies reveal that both Cs+ and CH2Cl2 sensing processes are rapid within 60 seconds. The corresponding limit of detection (LOD) values for sensing Cs+ and CH2Cl2 are as low as 0.37 mM and 0.37%. Moreover, it was also verified that Cs+ sensing is applicable in the range of pH = 7-11 and the reversibility of sensor H2Qj can be easily achieved by modulating pH values, and H2Qj is also assessed for its Cs+ sensing performces in real water samples. This H2Qj-Cs sensing system must provide a valuable reference for further Cs+ sensors.

An excellent colorimetric and "turn off" fluorescent probe for tetrahydrofuran based on a luminescent macrocyclic samarium(iii) complex.

In this paper we report a novel probe based on a luminescent 23-membered [1 + 1] Schiff-base macrocyclic mononuclear Sm(iii) complex Sm-2e, originating from the dialdehyde H2Qe and 1,2-bis(2-aminoethoxy)ethane precursors, which is synthesized by the Sm(iii) ion template method. X-ray structural analyses confirm that each ten-coordinate Sm(iii) center with the coordination geometry of a distorted bicapped square antiprism is fully encapsulated by a flexible macrocyclic ligand H2L2e to form a "lasso-type" architecture, and this architecture could enable efficient energy transfer in various solvents confirmed by long lifetimes (33.5-65.2 µs) and high quantum yields (0.23-0.76%) of the Sm(iii) ion. Simultaneously, complex Sm-2e could serve as a probe for sensing organic solvents. Particularly, this complex probe Sm-2e exhibits a highly selective, rapid and sensitive response to tetrahydrofuran (THF), which is easily distinguished by a large absorption shift, even visible to the naked eye, and complete fluorescence quenching. Moreover, the limit of detection for THF is about 0.20% determined by titration experiments, and good selectivity for THF could still be realized in mixture solvents. Consequently, this colorimetric and "turn off" fluorescent probe Sm-2e could be a valuable candidate as a sensor material for sensing THF which has been rarely reported.

Polyphenol-sodium alginate supramolecular injectable hydrogel with antibacterial and anti-inflammatory capabilities for infected wound healing.

Injectable hydrogel has attracted appealing attention for skin wound treatment. Although multifunctional injectable hydrogels can be prepared by introducing bioactive ingredients with antibacterial and anti-inflammatory capabilities, their preparation remains complicated. Herein, a polyphenol-based supramolecular injectable hydrogel (PBSIH) based on polyphenol gallic acid and biological macromolecule sodium alginate is developed as a wound dressing to accelerate wound healing. We show that such PBSIH can be rapidly formed within 15 s by mixing the sodium alginate and gallic acid solutions based on the hydrogen bonding and hydrophobic interactions. The PBSIH shows excellent cytocompatibility, antibacterial, and antioxidant properties, which enhance infected wound healing by inhibiting bacterial infection and alleviating inflammation after treatment of 11 days. Moreover, we show that the preparative strategies of injectable supramolecular hydrogels can be extended to other polyphenols, including protocatechuic and tannic acids. This study provides a facile yet highly effective method to design injectable polyphenol- sodium alginate hydrogel for wound dressing based on naturally bioactive ingredients.

Acidity-activated aggregation and accumulation of self-complementary zwitterionic peptide-decorated gold nanoparticles for photothermal biofilm eradication.

Drug-resistant biofilm infection is an extremely serious clinical problem, that easily leads to failure of antibiotic treatment. Although gold nanoparticles (AuNPs) as photothermal agents have been widely used in biofilm eradication, there are still challenges to be addressed, such as insignificantly redshifted absorption and slow assembly process of aggregated AuNPs. Herein, we developed an acidity-activated dispersion-to-aggregation transition to enhance the accumulation of self-complementary zwitterionic peptide-decorated AuNPs for photothermal eradication of drug-resistant biofilm infections. AuNPs were decorated with self-complementary zwitterionic peptides (ZP1 and ZP2) coupled with pH-sensitive anhydride (DMA) and pH-insensitive anhydride (SA), respectively. ZP2-decorated AuNPs with DMA modification (AuNP@ZP2(DMA)) exhibited prolonged blood circulation and enhanced accumulation in acidic biofilm microenvironment. Moreover, the electrostatic attraction between self-complementary ligands drove AuNPs to form closely packed aggregates with strong near-infrared absorption, leading to in vivo photoacoustic imaging ability and photothermal effect against drug-resistant bacteria and fungus, as well as microbial biofilms. AuNP@ZP2(DMA) with longer charge domains and a polyethylene glycol oligomer spacer showed greater photothermal antimicrobial and biofilm resistance in vitro and in vivo. This study develops an innovative acidity-activated AuNP photothermal agent, which provides an effective approach for treatment of biofilm infections.

Autophagy activator-loaded bicomponent peptide nanocarriers for phototherapy-triggered immunity enhancement against metastatic breast cancer.

Mild autophagy accompanied with immunogenic cell death (ICD) effect destructs immune-associated antigens, weakening the immune response against tumor growth. To address this dilemma, we develop a peptide-based bicomponent nanocarrier with encapsulation of a cellular hyperautophagy activator (STF-62247) for near-infrared (NIR) photo/immunotherapy to eliminate primary and metastatic breast tumors. The electrostatic-driven nanodrug (PPNPs@STF) with active-targeting and efficient endosomal escape can induce specific ICD effect upon NIR laser irradiation, and trigger autophagy to a mild activation state. Notably, the simultaneously released STF-62247 precisely promotes autophagy to an overactivated state, resulting in autophagic death of tumor cells and further boosting ICD-related antigen presentation. More importantly, the combined photo/immunotherapy of PPNPs@STF not only inhibits tumor cell proliferation, but also promotes dendritic cells (DCs)-associated immune response. In 4 T1 tumor-bearing mice, PPNPs@STF effectively inhibits growth of primary and distant tumors, and suppresses lung metastasis with a minimized side effect. This study provides a hyperautophagy activator-assisted strategy that can enhance ICD-based antitumor immune response for the treatment of metastatic breast cancer.

Supramolecular H-Aggregates of Squaraines with Enhanced Type I Photosensitization for Combined Photodynamic and Photothermal Therapy.

Combined photodynamic and photothermal therapy (PDT and PTT) can achieve more superior therapeutic effects than the sole mode by maximizing the photon utilization, but there remains a significant challenge in the development of related single-molecule photosensitizers (PSs), particularly those with type I photosensitization. In this study, self-assembly of squaraine dyes (SQs) is shown to be a promising strategy for designing PSs for combined type I PDT and PTT, and a supramolecular PS (TPE-SQ7) has been successfully developed through subtle molecular design of an indolenine SQ, which can self-assemble into highly ordered H-aggregates in aqueous solution as well as nanoparticles (NPs). In contrast to the typical quenching effect of H-aggregates on reactive oxygen species (ROS) generation, our results encouragingly manifest that H-aggregates can enhance type I ROS (•OH) generation by facilitating the intersystem crossing process while maintaining a high PTT performance. Consequently, TPE-SQ7 NPs with ordered H-aggregates not only exhibit superior combined therapeutic efficacy than the well-known PS (Ce6) under both normoxic and hypoxic conditions but also have excellent biosafety, making them have important application prospects in tumor phototherapy and antibacterial fields. This study not only proves that the supramolecular self-assembly of SQs is an effective strategy toward high-performance PSs for combined type I PDT and PTT but also provides a different understanding of the effect of H-aggregates on the PDT performance.

Endogenous stimuli-responsive separating microneedles to inhibit hypertrophic scar through remodeling the pathological microenvironment.

Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.

Optimized Charge/Hydrophobicity Balance of Antimicrobial Peptides Against Polymicrobial Abdominal Infections.

Antimicrobial peptides (AMPs) potentially serve as ideal antimicrobial agents for the treatment of polymicrobial abdominal infections due to their broad-spectrum antimicrobial activity and excellent biocompatibility. However, the balance of chain length, positive charges, and hydrophobicity on the antimicrobial activity of AMPs are still far from being optimal. Herein, a series of AMPs ([KX]n -NH2 , X = Ile, Leu or Phe, n = 3, 4, 5, or 6) with varied charges and hydrophobicity for the treatment of polymicrobial abdominal infections are designed. Specifically, [KI]4 -NH2 peptide exhibits the best in vitro antimicrobial activity against Gram-positive and -negative bacteria, as well as fungal strains. Based on the good cell biocompatibility, [KI]4 -NH2 peptide is found to have negligible in vivo toxicity at the dosage of up to 28 mg kg-1 . Furthermore, great in vivo therapeutic efficacy of [KI]4 -NH2 peptide against S. typhimurium is demonstrated in the mice abdominal infection model. The design of short sequence of antimicrobial peptides with a charge/hydrophobicity balanced structures provides a simple and efficient strategy for potential clinical applications of antimicrobial peptide-based biomaterials in a variety of bacterial infection diseases.

Luminescent Sm(III) complex bearing dynamic imine bonds as a multi-responsive fluorescent sensor for F- and PO43- anions together with Zn2+ cation in water samples.

We have designed and synthesized a new luminescent mononuclear samarium (III) complex Sm-2h based on the [1 + 1] Schiff-base macrocycle H2L2h, derived from the cyclocondensation reaction between dialdehyde and diamine precursors, and its exact architecture is determined to be [Sm(HL2h) (NO3)2]. The sensing ability of complex Sm-2h is carefully evaluated for various common inorganic ions in solution. It is shown that complex Sm-2h is a multi-responsive fluorimetric sensor with high selectivity for F- and PO43- anions together with Zn2+ cation. The sensing process is rapid within 60 s for F- and PO43- ions and 300 s for Zn2+ ion. Further detailed responsive investigations suggest that its sensing behavior has excellent linear relationship between the fluorescence intensity (or absorption value) and ion concentration. The limit of detection (LOD) for sensing F-, PO43- and Zn2+ ions are as low as 2.61 µM (2.94 µM), 1.92 µM (1.64 µM) and 5.67 µM (3.53 µM), respectively, verified by fluorimetric (or colorimetric) titration experiments. ESI mass spectra prove that these efficient detections originate from the structure collapse of sensor Sm-2h because of the ion-induced imine bond breakage. Moreover, sensor Sm-2h shows excellent sensing performances for F-, PO43- and Zn2+ ions in real water samples, and we also have developed a convenient method to detect these three ions by use of the sensor impregnated test paper strips, providing rapid and distinguishable fluorimetric color changes. Therefore, the macrocyclic Sm(III) complex Sm-2h could be regarded as a valuable candidate for monitoring F-, PO43- and Zn2+ ions in practical applications.

Series of Highly Luminescent Macrocyclic Sm(III) Complexes: Functional Group Modifications Together with Luminescence Performances in Solid-State, Solution, and Doped Poly(methylmethacrylate) Film.

Here, we report our trials to regulate the luminescence performance of the macrocyclic samarium(III) complex and prepare four excellent luminescent Sm(III) complex-doped poly(methylmethacrylate) (PMMA) composites. Four 23-membered [1 + 1] Schiff-base macrocyclic mononuclear Sm(III) complexes, Sm-2 a -Sm-2 d , originating from dialdehydes with different pendant arms and 1,2-bis(2-aminoethoxy)ethane, have been constructed by the template method. Crystal structures reveal that every Sm(III) ion with the coordination geometry of a distorted bicapped square antiprism is capsulated by the macrocyclic cavity environment forming the "lasso-type" protection. Relative photophysical properties of macrocyclic Sm(III) complexes are carefully investigated in solid-state, methanol solution, and doped PMMA film, and all these show characteristic emissions of the Sm(III) ion associated with satisfactory lifetimes and quantum yields in all media, which could be comparable to reported outstanding examples. Especially, the luminescence performance for this type of Sm(III) complex could be regulated in the solid state by the use of different functional groups in the pendant arm while it is not achieved in solution and the doped PMMA composite. High emitting and air-stable plastic materials could be obtained when these Sm(III) complexes are doped in PMMA with 0.1 wt % mixing ratio, and the corresponding maximum lifetime and quantum yield are 61.2 µs and 0.63% in the case of complex Sm-2 a , respectively. We believe that these highly luminescent "lasso-type" Sm(III) complexes and doped PMMA composites are valuable references in the design of luminescent lanthanide(III) hybrid materials.