다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

An overview of the use of nanozymes in antibacterial applications

The development of alternative strategies for the efficient treatment of subcutaneous abscesses that do not require the massive use of antibiotics and surgical intervention is urgently needed. Herein, a novel synergistic antibacterial strategy based on photodynamic (PDT) and NO gas therapy is reported, in which, a PDT-driven NO controllable generation system (Ce6@Arg-ADP) is developed with l-Arg-rich amphiphilic dendritic peptide (Arg-ADP) as a carrier. This carrier not only displays superior bacterial association and biofilm penetration performance, but also acts as a versatile NO donor. Following efficient penetration into the interior of the biofilms, Ce6@Arg-ADP can rapidly produce massive NO via utilizing the H2 O2 generated during PDT to oxidize Arg-ADP to NO and l-citrulline, without affecting singlet oxygen (1 O2 ) production. The combination of 1 O2 and the reactive by-products of NO offers notable synergistic antibacterial and biofilm eradication effects. Importantly, following efficient elimination of all bacteria from the abscess site, Arg-ADP can further generate trace quantities of NO to facilitate the angiogenesis and epithelialization of the wound tissues, thereby notably promotes wound healing. Together, this study clearly suggests that Arg-ADP is a versatile NO donor, and the combination of PDT and NO represents a promising strategy for the efficient treatment of subcutaneous abscesses.

L-Arg-Rich Amphiphilic Dendritic Peptide as a Versatile NO Donor for NO/Photodynamic Synergistic Treatment of Bacterial Infections and Promoting Wound Healing

Bacterial biofilm infections are intractable to traditional antibiotic treatment and usually cause persistent inflammation. Chemodynamic therapy (CDT) based on the Fenton reaction has recently emerged as a promising anti-biofilm strategy. However, the therapeutic efficacy of current Fenton agents often suffers from inefficient Fenton activity and lacks anti-inflammatory capability. Herein, FePS3 nanosheets (NSs) are explored for the first time as novel microenvironment-selective therapeutic nanoagents for bacterial biofilm infections with both self-enhanced Fenton activity for an anti-biofilm effect and reactive oxygen species (ROS) scavenging properties for an anti-inflammatory effect. In biofilms with acidic microenvironments, FePS3 NSs release Fe2+ to generate toxic ROS by Fenton reaction and reductive [P2S6]4- to enhance the Fenton activity by reducing Fe3+ to Fe2+. In the surrounding normal tissues with neutral pH, FePS3 NSs scavenge ROS by reductive [P2S6]4- with an anti-inflammatory effect. This work demonstrates multifunctional Fenton nanoagents with microenvironment-selective ROS generation and elimination properties for effective treatment of bacterial biofilm infections with both anti-biofilm and anti-inflammatory effects.

A multifunctional Fenton nanoagent for microenvironment-selective anti-biofilm and anti-inflammatory therapy.

Bacterial biofilm related infections are ever growing issues for global medical community. Traditional antibiotic therapy is usually ineffective for treating them because the bacteria inside biofilms have evolved with multiple mechanisms to evade antibiotic challenge. Hence, effective therapeutic strategy with novel antibiofilm mode of action is highly desired. In this context, nanomedicine has drawn great attentions and has been proven promising to prevent and eliminate bacterial biofilms. In this review, we focus on the recent advance of nanotechnology‐based strategies and nanoagents for combating bacterial biofilm infections. First, typical antibiofilm nanotechnologies utilized different chemical, physical, and biological properties of nanomaterials are discussed. Second, smart nanoagents that can responsive to biofilm microenvironment, including pH, H2O2, and enzymes, are shown. Third, some promising antibiofilm approaches, such as theranostics, biofilm structure destruction, and quorum sensing inhibition, are also demonstrated. Finally, we conclude the current antibiofilm nanotechnologies and discuss the challenges and future directions in this field.

Recent development of nanomedicine for the treatment of bacterial biofilm infections

Infectious diseases associated with antibiotic-resistant bacteria are ever-growing threats to public health. Effective treatment and detection methods of bacterial infections are in urgent demand. Herein, novel phototheranostic nanoagents (MoS2@HA–Ce6 nanosheets, MHC NSs) with hyaluronidase (HAase)-responsive fluorescence imaging (FLI) and photothermal/photodynamic therapy (PTT/PDT) functions were prepared. In this design, Ce6 is used as both a photosensitizer and a fluorescent probe, while MoS2 nanosheets (MoS2 NSs) serve as both a fluorescence quencher and a photothermal agent. Hyaluronic acid conjugated with Ce6 (HA–Ce6) was assembled on the surface of MoS2 NSs to form MHC NSs. Without the HAase secreted by methicillin-resistant Staphylococcus aureus (MRSA), the fluorescence of Ce6 is quenched by MoS2 NSs, while in the presence of MRSA, HAase can degrade the HA and release Ce6, which restores the fluorescence and photodynamic activity of Ce6. The experimental results show that MHC NSs can fluorescently image the MRSA both in vitro and in vivo by HAase activation. Meanwhile, MHC NSs can serve as PTT/PDT dual-mode antibacterial agents for MRSA. In vitro antibacterial results show that MHC NSs can kill 99.97% MRSA under 635 nm and 785 nm laser irradiation. In vivo study further shows that MHC NSs can kill 99.9% of the bacteria in MRSA infected tissues in mice and prompt wound healing by combined PTT/PDT. This work provides novel HAase-responsive phototheranostic nanoagents for effective detection and treatment of bacterial infections.

Hyaluronidase-responsive phototheranostic nanoagents for fluorescence imaging and photothermal/photodynamic therapy of methicillin-resistant Staphylococcus aureus infections

The synergy of chemodynamic therapy (CDT) and photothermal therapy (PTT) can improve anticancer efficacy, while the limited diffusion distance and the short lifetime of •OH still greatly restrict the therapeutic efficacy of PTT-CDT. Herein, MoS2@PDA-Fe@PEG/TPP (MPFPT) nanosheets (NSs) with mitochondria-targeting ability were reported for enhanced PTT-CDT synergistic oncotherapy. MPFPT NSs were prepared by covalent modification of poly(ethylene glycol) (PEG) and triphenylphosphonium (TPP) on polydopamine (PDA)-Fe3+coated MoS2 NSs. Co-localization experiments showed that MPFPT NSs can efficiently target mitochondria via the direction of TPP. Moreover, MPFPT NSs have good photothermal performance in the second near-infrared (NIR-II) region and can greatly accelerate the Fenton reaction from H2O2 to generate more hydroxyl radicals (•OH). In vitro experimental results showed that MPFPT NSs have improved therapeutic efficacy to cancer cells than similar MoS2-based nanoagents without mitochondria-targeting units, which can be attributed to the short distance between mitochondria and MPFPT NSs and the efficient damage of mitochondria by in situ generated •OH. In the 4T1 tumor-bearing mice model, MPFPT NSs demonstrated significantly enhanced therapeutic efficacy by PTT-CDT, suggesting the superiority of the mitochondria-targeting strategy. This study reveals that mitochondria-targeting MPFPT NSs are promising nanoagents for oncotherapy.

Mitochondria-Targeting MoS2-Based Nanoagents for Enhanced NIR-II Photothermal-Chemodynamic Synergistic Oncotherapy.

Furin is an important cellular endoprotease, which is expressed at high levels in various cancer cells. Accurate and real-time detection of endogenous furin with high sensitivity and selectivity is significant for the diagnosis of cancer. Herein an activatable nanoprobe (MoS2@PDA-PEG/peptide, MPPF) with dual-mode near-infrared fluorescence (NIRF)/ratiometric photoacoustic (PA) imaging of endogenous furin activity has been developed. The MPPF nanoprobes were constructed by the covalent functionalization of polydopamine (PDA) coated MoS2 nanosheets (NSs) with Cy7-labeled furin substrate peptides. Upon cleavage of the peptides by furin, Cy7 molecules are released from MPPF nanoprobes and recover their fluorescence, realizing furin activity detection with the limit of detection (LOD) down to 3.73 × 10-4 U mL-1. Meanwhile, the ratio of the PA signal at 768 nm to that at 900 nm (PA768/PA900) decreases over time due to the destruction of fluorescence resonance energy transfer effect from Cy7 to MoS2 NSs and the rapid clearance of small Cy7 molecules from tissues. Thus, the simultaneous change in NIRF and ratiometric PA signals enables the imaging of endogenous furin activity in real time, and with high sensitivity, and high selectivity in both tumor cells and tumor-bearing mice.

Fluorescence and ratiometric photoacoustic imaging of endogenous furin activity via peptide functionalized MoS2 nanosheets.

The invention discloses transition metal chalcogenide nano dots and a preparation method thereof. A polymer and an inorganic salt are adopted as a binary assistant to assist in ball-milling, and the preparation method comprises the following steps: weighing the polymer powder, the inorganic salt and a transition metal chalcogenide block powder according to a mass ratio of (0.1-200): (0.1-10): 1, adding an obtained mixture into a dry ball-milling tank, and sufficiently mixing with ball-milling balls; fixing the ball-milling tank in a ball mill, and stripping the transition metal chalcogenide block powder into the transition metal chalcogenide nanodots by using the ball mill; after ball milling is finished, repeatedly washing with ultrapure water for multiple times until all products obtained after ball milling stripping are taken out; carrying out gradient centrifugation on the products obtained in the previous step, discarding a material which is not completely stripped from a lower layer under low-speed centrifugation, collecting an upper-layer solution, carrying out centrifugal purification for multiple times to remove the excess polymer and the excess inorganic salt, and dispersing an obtained small-size nano dot product into ultrapure water. The preparation method is simple, efficient, high in yield, low in product price and uniform in size.

Hang Xiao

Papers

Recent development of nanomedicine for the treatment of bacterial biofilm infections

Hyaluronidase-responsive phototheranostic nanoagents for fluorescence imaging and photothermal/photodynamic therapy of methicillin-resistant Staphylococcus aureus infections

Mitochondria-Targeting MoS2-Based Nanoagents for Enhanced NIR-II Photothermal-Chemodynamic Synergistic Oncotherapy.

Fluorescence and ratiometric photoacoustic imaging of endogenous furin activity via peptide functionalized MoS2 nanosheets.

Transition metal chalcogenide nano dots and preparation method thereof