Wireless Powered Microwave-Light Conversion Platform with Dual-Stimulus Nanoresponder Coating for Deep-Seated Photodynamic Therapy.

Traditional external field-assisted therapies, e.g., microwave (MW) therapy and phototherapy, cannot effectively and minimally damage eliminate deep-seated infection, owing to the poor penetrability of light and low reactive oxygen species (ROS) stimulation capability of MW. Herein, an implantable and wireless-powered therapeutic platform (CNT-FeTHQ-TS), in which external MW can be converted into internal light via MW wireless-powered light-emitting chips, is designed to eradicate deep-seated tissue infections by MW-induced deep-seated photodynamic therapy. In application, CNT-FeTHQ-TS is implanted at internal lesions, and the chip emits light under external MW irradiation. Subsequently, CNT-FeTHQ coating in the platform can respond to both MW and light simultaneously to generate ROS and MW-hyperthermia for rapid and precise sterilization at focus. Importantly, MW also improves the photodynamic performance of CNT-FeTHQ by introducing vacancies in FeTHQ to facilitate the photoexcitation process and changing the spin state of electrons to inhibit the complexation of photogenerated electron-hole pairs, which were confirmed by simulation calculations and in situ MW-irradiated photoluminescence experiments. In vivo, CNT-FeTHQ-TS can effectively cure mice with Staphylococcus aureus infection in dorsal subcutaneous tissue. This work overcomes the key clinical limitations of safe energy transmission and conversion for treating deep-seated infections.

A Smart Bacteria-Capture-Killing Vector for Effectively Treating Osteomyelitis Through Synergy Under Microwave Therapy.

Osteomyelitis caused by deep tissue infections is difficult to cure through phototherapy due to the poor penetration depth of the light. Herein, Cu/C/Fe3O4-COOH nanorod composites (Cu/C/Fe3O4-COOH) with nanoscale tip convex structures are successfully fabricated as a microwave-responsive smart bacteria-capture-killing vector. Cu/C/Fe3O4-COOH exhibited excellent magnetic targeting and bacteria-capturing ability due to its magnetism and high selectivity affinity to the amino groups on the surface of Staphylococcus aureus (S. aureus). Under microwave irradiation, Cu/C/Fe3O4-COOH efficiently treated S. aureus-infected osteomyelitis through the synergistic effects of microwave thermal therapy, microwave dynamic therapy, and copper ion therapy. It is calculated the electric field intensity in various regions of Cu/C/Fe3O4-COOH under microwave irradiation, demonstrating that it obtained the highest electric field intensity on the surface of copper nanoparticles of Cu/C/Fe3O4-COOH due to its high-curvature tips and metallic properties. This led to copper nanoparticles attracted more charged particles compared with other areas in Cu/C/Fe3O4-COOH. These charges are easier to escape from the high curvature surface of Cu/C/Fe3O4-COOH, and captured by adsorbed oxygen, resulting in the generation of reactive oxygen species. The Cu/C/Fe3O4-COOH designed in this study is expected to provide insight into the treatment of deep tissue infections under the irradiation of microwave.

Enhancing Microwave Dynamic Effects via Surface States of Ultrasmall 2D MOF Triggered by Interface Confinement for Antibiotics-Free Therapy.

Microwave (MV)-trigged dynamic therapy based on MV-responsive materials is promising for treating deep infection diseases that cannot be effectively treated by antibiotics, like life-threatening osteomyelitis. Surface states of materials affect the generation of free charges under the excitation source with energy less than the band gap, consequently influencing the MV dynamic effects. Herein, an MV responsive system with interface confined 2D metal-organic framework (2D MOF) on oxidized carbon nanotube (CNT) is prepared, in which the ultrasmall Cu-based 2D MOF possesses sufficient surface/interface defects, endowing the system a large number of surface states. Under MV irradiation, the synthesized CNT-2D MOF not only efficiently absorbs and converts the microwave into heat for microwaveocaloric therapy (MCT) via enhanced hetero-interfacial polarization, but also generates excited electrons via surface state for microwave dynamic therapy (MDT). This biocompatible CNT-2D MOF exhibits highly effective broad-spectrum antimicrobial activity against seven pathogenic bacteria, including Gram-negative and Gram-positive pathogens, under 7 min MV irradiation. And this system is proven to efficiently eradicate Staphylococcus aureus infected rabbit tibia osteomyelitis. Significantly, MV-excited MCT and MDT of CNT-CuHHTP developed in this study makes a major step forward in antibiotic-free MV therapy in deep tissue bacterial infection diseases.

Rapid Ferroelectric-Photoexcited Bacteria-Killing of Bi4Ti3O12/Ti3C2T x Nanofiber Membranes.

In this study, an antibacterial nanofiber membrane [polyvinylidene fluoride/Bi4Ti3O12/Ti3C2T x (PVDF/BTO/Ti3C2T x )] is fabricated using an electrostatic spinning process, in which the self-assembled BTO/Ti3C2T x heterojunction is incorporated into the PVDF matrix. Benefiting from the internal electric field induced by the spontaneously ferroelectric polarization of BTO, the photoexcited electrons and holes are driven to move in the opposite direction inside BTO, and the electrons are transferred to Ti3C2T x across the Schottky interface. Thus, directed charge separation and transfer are realized through the cooperation of the two components. The recombination of electron-hole pairs is maximumly inhibited, which notably improves the yield of reactive oxygen species by enhancing photocatalytic activity. Furthermore, the nanofiber membrane with an optimal doping ratio exhibits outstanding visible light absorption and photothermal conversion performance. Ultimately, photothermal effect and ferroelectric polarization enhanced photocatalysis endow the nanofiber membrane with the ability to kill 99.61% ± 0.28% Staphylococcus aureus and 99.71% ± 0.16% Escherichia coli under 20 min of light irradiation. This study brings new insights into the design of intelligent antibacterial textiles through a ferroelectric polarization strategy. Supplementary Information: The online version contains supplementary material available at 10.1007/s42765-022-00234-8.

Interfacial Mo, W-Conjugated Polarization, and Oxygen Vacancies of MoO2/WO3 in Enhanced Microwave Therapy for MRSA-Induced Osteomyelitis.

Deep tissue infection, such as osteomyelitis, caused by methicillin-resistant Staphylococcus aureus (MRSA) infection, poses a serious threat to public health and cannot be effectively treated by antibiotics. In this study, we report a microwave (MW)-responsive MoO2/WO3 heterojunction that can be utilized to effectively treat MRSA-infected osteomyelitis under MW irradiation because of the enhanced MW thermal effect and MW catalysis of the composite. The underlying mechanism is as follows: A myriad of oxygen vacancies forms on the surface of MoO2 and WO3 by deoxidization effect with hydrogen from the decomposition of sodium borohydride, which induces a mass of free electrons on the surface of the composite and consequently promotes a localized surface plasmon resonance effect (LSPR) under MW irradiation. Furthermore, the conjugation of Mo and W at the interface enhances the LSPR effect. Thus, the LSPR effect not only induces the formation of radical oxygen species, thereby enhancing MW catalysis, but also results in the formation of an interfacial electrical field, which strengthens dipole polarization through synergistic action with oxygen vacancies and contributes to better MW thermal effects. The characteristics of MoO2/WO3 prove to be promising for the treatment of deep-tissue infections under MW irradiation.

Sea urchin-like Bi2S3/curcumin heterojunction rapidly kills bacteria and promotes wound healing under near-infrared light.

Bacterial infection is an urgent public health problem. We design a novel photo-responsive hybrid material by growing small molecules of curcumin (Cur) in situ on a sea urchin-like Bi2S3 surface by a one-step hydrothermal reaction method, thus forming an organic-inorganic hybrid material with interfacial contact. The Bi2S3/Cur hybrid material has good antibacterial effect under 808 nm near-infrared (NIR) light irradiation. The antibacterial mechanism is that the electron redistribution at the interface of Bi2S3/Cur excited by 808 nm NIR light will cause a large number of electrons to gather on the side of Bi2S3, forming an internal electric field to drive the excited electrons from Bi2S3 to Cur, which accelerates the separation of photoexcited electron-hole pairs and enhances the production of reactive oxygen species (ROS). In conclusion, due to these synergistic effects of the photothermal properties of Bi2S3, the production of more ROS and the release of small molecules of Cur from traditional Chinese medicine in Bi2S3/Cur, the antibacterial efficacy against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) is 99.96% and 99.03%, respectively. In vivo experiments in animals show that Bi2S3/Cur can reduce the inflammatory response and promote wound healing. This paper presents a simple, rapid and safe strategy for the treatment of wound infections with near-infrared light.

Microwave assisted antibacterial action of Garcinia nanoparticles on Gram-negative bacteria.

Owing to the existence of the outer membrane barrier, most antibacterial agents cannot penetrate Gram-negative bacteria and are ineffective. Here, we report a general method for narrow-spectrum antibacterial Garcinia nanoparticles that can only be effective to kill Gram-positive bacteria, to effectively eliminate Gram-negative bacteria by creating transient nanopores in bacterial outer membrane to induce drug entry under microwaves assistance. In vitro, under 15 min of microwaves irradiation, the antibacterial efficiency of Garcinia nanoparticles against Escherichia coli can be enhanced from 6.73% to 99.48%. In vivo, MV-assisted GNs can effectively cure mice with bacterial pneumonia. The combination of molecular dynamics simulation and experimental results reveal that the robust anti-E. coli effectiveness of Garcinia nanoparticles is attributed to the synergy of Garcinia nanoparticles and microwaves. This work presents a strategy for effectively treating both Gram-negative and Gram-positive bacteria co-infected pneumonia using herbal medicine nanoparticles with MV assistance as an exogenous antibacterial auxiliary.

Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing.

Owing to the poor penetration depth of light, phototherapy, including photothermal and photodynamic therapies, remains severely ineffective in treating deep tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis. Here, we report a microwave-excited antibacterial nanocapturer system for treating deep tissue infections that consists of microwave-responsive Fe3O4/CNT and the chemotherapy agent gentamicin (Gent). This system, Fe3O4/CNT/Gent, is proven to efficiently target and eradicate MRSA-infected rabbit tibia osteomyelitis. Its robust antibacterial effectiveness is attributed to the precise bacteria-capturing ability and magnetic targeting of the nanocapturer, as well as the subsequent synergistic effects of precise microwaveocaloric therapy from Fe3O4/CNT and chemotherapy from the effective release of antibiotics in infection sites. The advanced target-nanocapturer of microwave-excited microwaveocaloric-chemotherapy with effective targeting developed in this study makes a major step forward in microwave therapy for deep tissue infections.

Screening for strains with 11α-hydroxylase activity for 17α-hydroxy progesterone biotransformation.

Various corticosteroids are prepared by using 11α,17α-diOH-progesterone (11α,17α-diOH-PROG) as an important intermediate and raw material. Hence, strains that can improve the yields of 11α,17α-diOH-PROG should be screened. Cunninghamella elegans CICC40250 was singled out from five common 11α hydroxylation strains. The reaction parameters of 11α,17α-diOH-PROG production were also investigated. C. elegans CICC40250 could efficiently catalyze the hydroxylation of 17α-hydroxy progesterone (17α-OH-PROG) at C-11α position. This strain could also effectively convert 11α,17α-diOH-PROG at high substrate concentrations (up to 30g/L). After the coenzyme precursor glucose was added, the rate of 11α,17α-diOH-PROG formation reached 84.2%, which was 11.4% higher than that of the control group. Our study established a simple and feasible mechanism to increase 11α,17α-diOH-PROG production levels. This mechanism involves C. elegans CICC40250 that can be efficiently applied to induce the biotransformation of 17α-OH-PROG with a hydroxylation biocatalytic ability.

Biocatalyst-mediated production of 11,15-dihydroxy derivatives of androst-1,4-dien-3,17-dione.

Hydroxylation of steroids at various positions is a powerful tool for the production of valuable pharmaceutical ingredients and precursors. Our paper reported the synchronous dihydroxylation of an efficient strain, i.e., Colletotrichum lini AS3.4486, at two points. C. lini AS3.4486 was selected from 10 strains; this strain can catalyze the dihydroxylation of androst-1,4-dien-3,17-dione at C-11α and C-15α positions. Transformation of ADD(I) by C. lini AS3.4486 produced metabolites II-IV. The structures of these compounds were elucidated by liquid chromatography-mass spectrometry (LC-MS), Fourier Transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and X-ray as 15-hydroxyandrost-1,4-dien-3,17-dione (15α-OH-ADD; II), 11,15-dihydroxyandrost-1,4-dien-3,17-dione (11,15-diOH-ADD; III), and 15,17ß-dihy-droxyandrost-1,4-dien-3-one (15-OH-BD; BD is the abbreviation of boldenone; IV). III, as a novel compound, was reported for the first time. The course of conversion and mechanism about dihydroxylation reaction was also investigated. On the basis of time course analysis of hydroxylation, I underwent regioselective hydroxylation at 15 position and was subsequently converted to III and IV. Enzyme inhibition analysis showed that 11- and 15-hydroxylations were catalyzed by different hydroxylases. The effect of substrate concentration on I transformation was also determined. Results showed that the optimum concentration of I was 20 g/L, and the yield of III was up to 18.8 g/L.

The effect of 3-ketosteroid-Δ(1)-dehydrogenase isoenzymes on the transformation of AD to 9α-OH-AD by Rhodococcus rhodochrous DSM43269.

Rhodococcus rhodochrous DSM43269 is well known for its 3-ketosteroid-9α-hydroxylases. However, the function of its 3-ketosteroid-Δ(1)-dehydrogenases (KSDD) remains unknown. This study compared the involvement of ksdds in the strain's androst-4-ene-3,17-dione (AD) transformation via gene deletion. The conversion was performed using AD as substrate or directly with 9α-hydroxyandrost-4-ene-3,17-dione (9α-OH-AD). The single deletion of ksdd1 or ksdd3 did not appear to result in the accumulation of 9α-OH-AD, whereas the single mutant △ksdd2 could preserve this compound to some extent. To further compare the role of ksdds in this strain, double mutants were constructed. All ksdd2 mutants combined with ksdd1 and/or ksdd3 resulted in the accumulation of 9α-OH-AD, among which the double mutant △ksdd2,3 behaved similarly to the single mutant △ksdd2 in this process. The mutant that lacked both ksdd1 and ksdd3 was still displayed, with no effect on the degradation of 9α-OH-AD. The triple mutant △ksdd1,2,3 was then constructed and exhibited the same capability as △ksdd1,2, accumulating more 9α-OH-AD than △ksdd2,3 and △ksdd2. The transcription of KSDD1 and KSDD2 increased, whereas that of KSDD3 seemed to exhibit no change, despite the use of the inducer AD or 9α-OH-AD. Thus, only ksdd1 and ksdd2 were involved in the transformation of AD to 9α-OH-AD. ksdd2 had the main role, ksdd1 had a minor effect on 9α-OH-AD degradation, and ksdd3 did not exhibit any action in this course.