Renewable Electroconductive Hydrogels for Accelerated Diabetic Wound Healing and Motion Monitoring.

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes mellitus, may result in an amputation. Natural and renewable hydrogels are desirable materials for DFU dressings due to their outstanding biosafety and degradability. However, most hydrogels are usually only used for wound repair and cannot be employed to monitor motion because of their inherent poor mechanical properties and electrical conductivity. Given that proper wound stretching is beneficial for wound healing, the development of natural hydrogel patches integrated with wound repair properties and motion monitoring was expected to achieve efficient and accurate wound healing. Here, we designed a dual-network (chitosan and sodium alginate) hydrogel embedded with lignin-Ag and quercetin-melanin nanoparticles to achieve efficient wound healing and motion monitoring. The double network formed by the covalent bond and electrostatic interaction confers the hydrogel with superior mechanical properties. Instead of the usual chemical reagents, genipin extracted from Gardenia was used as a cross-linking agent for the hydrogel and consequently improved its biosafety. Furthermore, the incorporation of lignin-Ag nanoparticles greatly enhanced the mechanical strength, antibacterial efficacy, and conductivity of the hydrogel. The electrical conductivity of hydrogels gives them the capability of motion monitoring. The motion sensing mechanism is that stretching of the hydrogel induced by motion changes the conductivity of the hydrogel, thus converting the motion into an electrical signal. Meanwhile, quercetin-melanin nanoparticles confer exceptional adhesion, antioxidant, and anti-inflammatory properties to the hydrogels. The system ultimately achieved excellent wound repair and motion monitoring performance and was expected to be used for stretch-assisted safe and accurate wound repair in the future.

Bioengineered Bacterial Membrane Vesicles with Multifunctional Nanoparticles as a Versatile Platform for Cancer Immunotherapy.

Inducing immunogenic cell death (ICD) is a critical strategy for enhancing cancer immunotherapy. However, inefficient and risky ICD inducers along with a tumor hypoxia microenvironment seriously limit the immunotherapy efficacy. Non-specific delivery is also responsible for this inefficiency. In this work, we report a drug-free bacteria-derived outer membrane vesicle (OMV)-functionalized Fe3O4-MnO2 (FMO) nanoplatform that realized neutrophil-mediated targeted delivery and photothermally enhanced cancer immunotherapy. In this system, modification of OMVs derived from Escherichia coli enhanced the accumulation of FMO NPs at the tumor tissue through neutrophil-mediated targeted delivery. The FMO NPs underwent reactive decomposition in the tumor site, generating manganese and iron ions that induced ICD and O2 that regulated the tumor hypoxia environment. Moreover, OMVs are rich in pathogen-associated pattern molecules that can overcome the tumor immunosuppressive microenvironment and effectively activate immune cells, thereby enhancing specific immune responses. Photothermal therapy (PTT) caused by MnO2 and Fe3O4 can not only indirectly stimulate systemic immunity by directly destroying tumor cells but also promote the enrichment of neutrophil-equipped nanoparticles by enhancing the inflammatory response at the tumor site. Finally, the proposed multi-modal treatment system with targeted delivery capability realized effective tumor immunotherapy to prevent tumor growth and recurrence.

Mitochondria-Targeted Degradable Nanocomposite Combined with Laser and Ultrasound for Synergistic Tumor Therapies.

Although the development of safe and efficient cancer therapeutic agents is essential, this process remains challenging. In this study, a mitochondria-targeted degradable nanoplatform (PDA-MnO2-IR780) for synergistic photothermal, photodynamic, and sonodynamic tumor treatment was investigated. PDA-MnO2-IR780 exhibits superior photothermal properties owing to the integration of polydopamine, MnO2, and IR780. IR780, a photosensitizer and sonosensitizer, was used for photodynamic therapy and sonodynamic therapy. When PDA-MnO2-IR780 was delivered to the tumor site, MnO2 was decomposed by hydrogen peroxide, producing Mn2+ and oxygen. Meanwhile, alleviating tumor hypoxia promoted the production of reactive oxygen species during photodynamic therapy and sonodynamic therapy. Moreover, large amounts of reactive oxygen species could reduce the expression of heat shock proteins and increase the heat sensitivity of tumor cells, thereby improving the photothermal treatment effect. In turn, hyperthermia caused by photothermal therapy accelerated the production of reactive oxygen species in photodynamic therapy. IR780 selectively accumulation in mitochondria also promoted tumor apoptosis. In this system, the mutual promotion of photothermal therapy and photodynamic therapy/sonodynamic therapy had an enhanced therapeutic effect. Moreover, the responsive degradable characteristic of PDA-MnO2-IR780 in the tumor microenvironment ensured excellent biological safety. These results reveal a great potential of PDA-MnO2-IR780 for safe and highly-efficiency synergistic therapy for cancer.

Dual-Targeted Fe3O4@MnO2 Nanoflowers for Magnetic Resonance Imaging-Guided Photothermal-Enhanced Chemodynamic/Chemotherapy for Tumor.

The construction of high-efficiency tumor theranostic platform will be of great interest in the treatment of cancer patients; however, significant challenges are associated with developing such a platform. In this study, we developed high-efficiency nanotheranostic agent based on ferroferric oxide, manganese dioxide, hyaluronic acid and doxorubicin (FMDH-D NPs) for dual targeting and imaging guided synergetic photothermal-enhanced chemodynamic/chemotherapy for cancer, which improved the specific uptake of drugs at tumor site by the dual action of CD44 ligand hyaluronic acid and magnetic nanoparticles guided by magnetic force. Under the acidic microenvironment of cancer cells, FMDH-D could be decomposed into Mn2+ and Fe2+ to generate •OH radicals by triggering a Fenton-like reaction and responsively releasing doxorubicin to kill cancer cells. Meanwhile, alleviating tumor hypoxia improved the efficacy of chemotherapy in tumors. The photothermal properties of FMDH generated high temperatures, which further accelerated the generation of reactive oxygen species, and enhanced effects of chemodynamic therapy. Furthermore, FMDH-D NPs proved to be excellent T1/T2-weighted magnetic resonance imaging contrast agents for monitoring the tumor location. These results confirmed the considerable potential of FMDH-D NPs in a highly efficient synergistic therapy platform for cancer treatment.

[Cloning, expression and purification of D-carbamoylase from Sinorhizobium morelens S-5].

A N-carbamoyl-D-amino acid amidohydrolase gene (hyuC) from Sinorhizobium morelens S-5 was cloned by LA PCR, and its nucleotide sequence was determined. The deduced amino acid sequence encoded by the hyuC gene exhibited high homology to the amino acid sequences of D-carbamoylase from other sources. The gene could be highly expressed in Escherichia coli, and the recombinant enzyme was purified 16.1-fold to homogeneity with a yield of 21.2% by heat treatment and three steps of column chromatography. The results of gel filtration on Superdex 200 HR and SDS-polyacrylamide gel electrophoresis suggested that the enzyme was a tetramer protein of identical 38-kDa subunits. The recombinant enzyme catalyzed the hydrolysis of N-carbamoyl alpha-amino acid to the corresponding free amino acid, and it was strictly D-specific. The enzyme showed broad substrate specificity, and exhibited high activity in the hydrolysis of N-carbamoyl-D-p-hydroxyphenylglycine as substrate. The enzyme did not hydrolyze N-carbamoyl-beta-alanine. The optimum pH and temperature of the enzyme were pH 7.0 and 60 degrees C, respectively. Enzyme activity was slightly improved by Ca2+ and Fe2+, and nearly not affected by metal chelators and sulfhydryl reagents. The enzyme showed high thermal and oxidative stability. These results show that the enzyme has great potential for industrial application.