Tumor Microenvironment-Responsive Zn(II)-Porphyrin Nanotheranostics for Targeted Sonodynamic Therapy.

As a novel noninvasive tumor therapy, sonodynamic therapy (SDT) attracts booming concerns. However, the limited water solubility, inadequate biocompatibility, and low targeting ability of conventional sonosensitizers significantly hinder their potential for clinical application. Herein, novel zinc(II)-porphyrin nanotheranostics (HA@Zn-TCPP) were fabricated in which the zinc(II)-porphyrin (TCPP) metal-organic framework was first constructed by a simple thermal reaction, followed by the addition of hyaluronic acid (HA) for modification. The specific targeting ability of HA facilitated the internalization of HA@Zn-TCPP within tumor cells, resulting in its preferential accumulation in tumor tissues that exhibit CD44 receptor overexpression. The acidic tumor microenvironment induced the rapid decomposition of HA@Zn-TCPP, releasing free TCPP for activating SDT. This controllable generation of reactive oxygen species (ROS) could effectively decrease damage to normal tissues. The HA@Zn-TCPP exhibited remarkable antitumor effects in experiments, achieving a tumor inhibition rate of up to 82.1% when under ultrasound. This finding provides an imperative strategy to develop novel sonosensitizers for enhanced SDT.

Oligolysine-based hydrogel dressing with antibacterial, anti-inflammatory, and tissue-adhesion activities for infected wound treatment.

Fabricating injectable hydrogel with multiple functions and effective promotion of wound repair has a great prospect in treatment of bacterial infected wounds. Herein, a pH/reactive oxygen species (ROS) dual responsive injectable hydrogel (PVBDL-gel) was constructed, the PVBDL-gel was cross-linked by dynamic Schiff base bonds and borate ester bonds between poly(vanillin acrylate-co-3 acrylamide phenylboronic acid-co-N,N-dimethylacrylamide) (P(VA-co-AAPBA-co-DMA)), oligolysines and polyvinyl alcohol (PVA). The anti-inflammatory drug, dexamethasone sodium phosphate (DEX), was encapsulated in this hydrogel. The hydrogel exhibited excellent degradability, stable rheology and suitable tissue adhesion, more importantly, which showing pH/ROS responsive ability and controllable releasing of DEX. In vitro and in vivo experiment results showed that the PVBDL-gel with good biocompatibility and efficient anti-infection ability can effectively eradicate 99.9 % of pathogenic bacteria within 3 h and promote the repair and regeneration of bacterial infection wounds. This novel multifunctional injectable hydrogel has great application in the field of bacterial infection wound repair.

Polysulfonium: Unveiling a Bioactive Polymer to Induce Immunogenic Cell Death for Anticancer Therapy.

Here we report a brand-new bioactive polymer featuring sulfonium moieties that exhibits the capability of inducing immunogenic cell death (ICD) for anticancer therapy. The optimized polysulfonium presents a wide spectrum of potent anticancer activity and remarkable selectivity. In-depth mechanistic studies reveal that the polymer exerts its cytotoxic effects on cancer cells through a membrane-disrupting mechanism. This further initiates the release of a plethora of damage-associated molecular patterns, effectively triggering ICD and resulting in systemic anticancer immune responses. Notably, the compound demonstrated significant efficacy in suppressing tumor growth in the B16-F10 melanoma tumor model. Furthermore, it exhibits robust immune memory effects, effectively suppressing tumor recurrence and metastasis in both the rechallenge model and the lung metastatic tumor model. To the best of our knowledge, the study represents the pioneering exportation of cationic polysulfoniums, showcasing not only their remarkable safety and efficacy against primary tumors but also their unique ability in activating long-term immune memory.

Injectable antibacterial hydrogels based on oligolysines for wound healing.

Generally, oligolysine has poor antibacterial effect and almost no antibacterial activity. Herein, low cost and easily available oligolysines were chosen to prepare injectable antibacterial hydrogel (PVAL-gel) for wound healing. The hydrogel network was formed by cross-linking vanillin acrylate-N, N-dimethylacrylamide copolymer P(VA-co-DMA), oligolysine and adipate dihydrazide through Schiff base bond. The obtained hydrogel PVAL-gel exhibited not only excellent self-healing capability and injectability, but also the efficient contact antibacterial ability and good inhibitory effects on E.coli and S.aureus. In vitro, 99.9 % of pathogenic bacteria was killed within 160 min. Furthermore, the injectable PVAL-gel could rapidly eradicate bacteria in infected wounds and notably enhance the healing of full-thickness skin wounds. Therefore, PVAL-gel is expected to be used as a high-end dressing for the treatment of infected skin wounds, which can promote wound healing.

Proanthocyanidins-based tandem dynamic covalent cross-linking hydrogel for diabetic wound healing.

Wound healing in diabetic patients presents significant challenges in clinical wound care due to high oxidative stress, excessive inflammation, and a microenvironment prone to infection. In this study, we successfully developed a multifunctional tandem dynamic covalently cross-linked hydrogel dressing aimed at diabetic wound healing. This hydrogel was constructed using cyanoacetic acid functionalized dextran (Dex-CA), 2-formylbenzoylboric acid (2-FPBA) and natural oligomeric proanthocyanidins (OPC), catalyzed by histidine. The resulting Dex-CA/OPC/2-FPBA (DPOPC) hydrogel can be dissolved triggered by cysteine, thereby achieving "controllable and non-irritating" dressing change. Furthermore, the incorporation of OPC as a hydrogel building block endowed the hydrogel with antioxidant and anti-inflammatory properties. The cross-linked network of the DPOPC hydrogel circumvents the burst release of OPC, enhancing its biosafety. In vivo studies demonstrated that the DPOPC hydrogel significantly accelerated the wound healing process in diabetic mice compared to a commercial hydrogel, achieving an impressive wound closure rate of 98 % by day 14. The DPOPC hydrogel effectively balanced the disrupted inflammatory state during the healing process. This dynamic hydrogel based on natural polyphenols is expected to be an ideal candidate for dressings intended for chronic wounds.

Oxydextran-based photodynamic antibacterial nanoplatform with broad-Spectrum antibacterial activity.

The compounding of polysaccharide macromolecules and antibacterial agents always has been the preferred strategy to prepare antibacterial products, attracting increasing interest. Herein, a novel acid-responsive oxidized dextran-based nanoplatform (OTP NP) has been fabricated for photodynamic antibacterial therapy by combing photosensitizer monoaminoporphyrin (TPP-NH2) with oxidized dextran (ODex) via the Schiff Base reaction. OTP NP of about 100 nm is composed of an inner hydrophobic core of 30 nm and peripheral polysaccharide macromolecules. The OTP NP killed 99.9 % of E. coli and S. aureus within 1.5 light cycles at a concentration of 200 µg/mL. Concurrently, OTP NP exhibited excellent cytocompatibility at a concentration of 1 mg/mL (about 5 folds bactericidal concentration). Particularly, except for the recognized antibacterial mechanism of photodynamic therapy, a novel mechanism of bacterial membrane damage was discovered: the bacterial cell membrane was peeled off and formed spherical particles that aggregated around the bacteria to accelerate bacterial apoptosis under the combined action of ROS and nanomaterials. Moreover, the slightly soluble drug levofloxacin (Lev) as a model drug was loaded into OTP NP to test its carrier function, providing a practicable strategy to design multifunctional polysaccharide-based photodynamic antibacterial materials.

A Review on Macroscopic and Microstructural Features of Metallic Coating Created by Pulsed Laser Material Deposition.

Owing to the unparalleled advantages in repairing of high value-add component with big size, fabricating of functionally graded material, and cladding to enhance the surface properties of parts, the laser material deposition (LMD) is widely used. Compared to the continuous wave (CW) laser, the controllability of the laser energy would be improved and the temperature history would be different under the condition of pulse wave (PW) laser through changing the pulse parameters, such as duty cycle and pulse frequency. In this paper, the research status of temperature field simulation, surface quality, microstructural features, including microstructures, microhardness, residual stress, and cracking, as well as corrosion behavior of metallic coating created by pulsed laser material deposition have been reviewed. Furthermore, the existing knowledge and technology gaps are identified while the future research directions are also discussed.

Wound Microenvironment-Responsive Protein Hydrogel Drug-Loaded System with Accelerating Healing and Antibacterial Property.

Growth factors play a vital role in wound healing, and novel hydrogel carriers suitable for growth factors have always been a research hotspot in the wound healthcare field. In this work, a wound microenvironment-responsive hydrogel drug-loading system was constructed by cross-linking of the internal electron-deficient polyester and bovine serum albumin (BSA) via catalyst-free amino-yne bioconjugation. The slightly acidic microenvironment of wound tissues induces the charge removal of BSA chains, thus releasing the basic fibroblast growth factor (bFGF) loaded through electrostatic action. Besides, the BSA chains in the gel network further endow their excellent biocompatibility and biodegradability, also making them more suitable for bFGF loading. The wound caring evaluation of the hydrogel in the full-thickness skin wound indicated that the protein-based hydrogel significantly promotes the proliferation and differentiation of fibroblasts, collagen accumulation, and epidermal layer stacking, thus significantly shortening the healing process. This strategy paved the way for broadening the application of the growth factors in the wound care field.

Poly-tetrahydropyrimidine Antibacterial Hydrogel with Injectability and Self-Healing Ability for Curing the Purulent Subcutaneous Infection.

Infections caused by pathogenic microorganisms have always been the Achilles heel in the clinic. In this work, to overcome this conundrum, we proposed an injectable multifunctional hydrogel material with outstanding antibacterial properties and self-healing properties and no adverse effects on health. The cross-linked hydrogel with three-dimensional (3D) networks was quickly formed via the dynamic Schiff base between amino-modified poly-tetrahydropyrimidine (PTHP-NH2) and multiple vanillin polymer P(DMA-VA) in 30 s. This hydrogel composite presents effective defense against both Gram-positive and Gram-negative bacteria, especially for the pyogenic Staphylococcus aureus. Moreover, the hydrogel showed almost no hemolysis and cytotoxicity. In vivo investigations indicated that hydrogels effectively killed S. aureus and protected against deterioration of inflammation. Besides, bioimaging of mice demonstrated that the hydrogel could be completely metabolized within 16 h. In a nutshell, given its outstanding antibacterial property and biocompatibility, the novel hydrogel could be an ideal candidate for the subcutaneous infection application.