Simultaneous Biofilm Disruption, Bacterial Killing, and Inflammation Elimination for Wound Treatment Using Silver Embellished Polydopamine Nanoplatform.

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.

Elastic Nanovaccine Enhances Dendritic Cell-Mediated Tumor Immunotherapy.

Nanovaccine-based immunotherapy (NBI) has the ability to initiate dendritic cell (DC)-mediated tumor-specific immune responses and maintain long-term antitumor immune memory. To date, the mechanism by which the mechanical properties of nanoparticles alter the functions of DCs in NBI remains largely unclear. Here, a soft mesoporous organosilica-based nanovaccine (SMONV) is prepared and the elasticity-dependent effect of the nanovaccine on the underlying DC-mediated immune responses is studied. It is found that the elasticity results in greater internalization of SMONV by DCs, followed by the induction of substantial cytosolic delivery of antigens via endosomal escape, leading to effective DC maturation and antigen cross-presentation. Impressively, elasticity enables SMONV to enhance lymphatic drainage of antigens in vivo, thus stimulating robust humoral and cellular immunity. The results from therapeutic tumor vaccination further reveal that subcutaneously administered SMONV effectively suppresses tumor growth in tumor-bearing mice by evoking antigen-specific CD8+ T-cell immune responses, mitigating regulatory T-cell-mediated immunosuppression, and increasing central memory and effector memory T-cell populations. Furthermore, combinatorial immunization with SMONV and anti-PD-L1 blocking antibodies results in an amplified therapeutic effect on tumor-bearing mice. These findings reveal the elastic effect of the nanovaccine on DC-mediated immune responses, and the prepared SMONV represents a facile and powerful strategy for antitumor immunotherapy.

Cu2 MoS4 Nanozyme with NIR-II Light Enhanced Catalytic Activity for Efficient Eradication of Multidrug-Resistant Bacteria.

Nanozymes with unique enzyme-like catalytic properties and versatile functionalities are particularly attractive for the treatment of bacterial infections, especially for combating drug-resistant bacteria. However, inherently low catalytic activity significantly limits their antibacterial performance. Herein, a new near-infrared II (NIR-II) light responsive nanozyme (Cu2 MoS4 nanoplates, CMS NPs) is developed for efficient eradication of multidrug-resistant (MDR) bacteria. CMS NPs with intrinsic dual enzyme-like property can generate reactive oxygen species (ROS) by catalysis. Importantly, CMS NPs show NIR-II light enhanced oxidase- and peroxidase-like catalytic activities to improve ROS generation for highly efficient killing of bacteria. In vitro results demonstrate that CMS NPs (40 µg mL-1 ) achieve rapid killing of 8 log MDR Escherichia coli and 6 log MDR Staphylococcus aureus (S. aureus) under NIR-II light irradiation (1064 nm, 1 W cm-2 ) in 10 min. Moreover, CMS NPs exhibit excellent therapeutic efficacy of MDR S. aureus infection in vivo as well as negligible toxicity to cells and animals, indicating their potential use as antibacterial agents. This work provides a novel antibacterial strategy by combining the catalytic generation of ROS and NIR-II photothermal effect of nanozymes for efficient treatment of MDR bacteria-related infections.

Two-dimensional ternary chalcogenide nanodots with spatially controlled catalytic activity for bacteria infected wound treatment.

Nanozymes hold great prospects for bacteria-infected wound management, yet the spatial control of their catalytic activity in infected area and normal tissues remains mired by the heterogeneity of tissue microenvironment. Here, we develop a novel two-dimensional ternary chalcogenide nanodots (Cu2MoS4, CMS NDs) with renal clearable ability and controlled catalytic activity for bacteria-infected wound treatment. The two-dimensional CMS NDs (∼4 nm) are prepared by a simple microwave-assisted chemical synthetic route. Our results show that CMS NDs not only have peroxidase-like activity in a pH-dependent manner (pH < 5.5). Based on the generation of hydroxyl radical (OH) by adding H2O2, CMS NDs show > 2 log bacterial inactivation for both Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli (E. coli) under the acidic condition. Moreover, CMS NDs show good biocompatibility and can be excreted by the kidney in mice. In vivo results display that CMS NDs show good therapeutic effect against bacteria infected wound in the presence of H2O2, but no damage for normal tissues. Taken together, this work provides a renal clearable two-dimensional nanozyme with spatially controlled catalytic activity for the treatment of wounds and bacterial infections on the skin surface.

Flexible nanoplatform facilitates antibacterial phototherapy by simultaneously enhancing photosensitizer permeation and relieving hypoxia in bacterial biofilms.

Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust physical and chemical defenses of the biofilms. Traditional antibacterial nanoplatforms face challenges in breaching the extracellular polymeric substances barrier to efficiently deliver photosensitizers deep into biofilms. Moreover, the prevalent hypoxia within biofilms restricts the success of oxygen-reliant phototherapy. In this study, we engineered a soft mesoporous organosilica nanoplatform (SMONs) by incorporating polyethylene glycol (PEG), catalase (CAT), and indocyanine green (ICG), forming SMONs-PEG-CAT-ICG (SPCI). We compared the antimicrobial efficacy of SPCI with more rigid nanoplatforms. Our results demonstrated that unique flexible mechanical properties of SPCI enable it to navigate through biofilm barriers, markedly enhancing ICG penetration in methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Notably, in a murine subcutaneous MRSA biofilm infection model, SPCI showed superior biofilm penetration and pharmacokinetic benefits over its rigid counterparts. The embedded catalase in SPCI effectively converts excess H2O2 present in infected tissues into O2, alleviating hypoxia and significantly boosting the antibacterial performance of phototherapy. Both in vitro and in vivo experiments confirmed that SPCI surpasses traditional rigid nanoplatforms in overcoming biofilm barriers, offering improved treatment outcomes for infections associated with bacterial biofilms. This study presents a viable strategy for managing bacterial biofilm-induced diseases by leveraging the unique attributes of a soft mesoporous organosilica-based nanoplatform. STATEMENT OF SIGNIFICANCE: This research introduces an innovative antimicrobial phototherapy soft nanoplatform that overcomes the inherent limitations posed by the protective barriers of bacterial biofilms. By soft nanoplatform with flexible mechanical properties, we enhance the penetration and delivery of photosensitizers into biofilms. The inclusion of catalase within this soft nanoplatform addresses the hypoxia in biofilms by converting hydrogen peroxide into oxygen in infected tissues, thereby amplifying the antibacterial effectiveness of phototherapy. Compared to traditional rigid nanoplatforms, this flexible nanoplatform not only promotes the delivery of therapeutic agents but also sets a new direction for treating bacterial biofilm infections, offering significant implications for future antimicrobial therapies.

Ultrasound-Stimulated "Exocytosis" by Cell-Like Microbubbles Enhances Antibacterial Species Penetration and Immune Activation Against Implant Infection.

Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm-associated implant infections. Nevertheless, biofilms hinder the penetration of anti-bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell-like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3 O4 nanoparticle-fabricated microbubbles and then loaded with hydroxyurea (EMB-Hu). Under ultrasound (US) stimulation, EMB-Hu undergoes a stable oscillation manner to act in an "exocytosis" mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti-bacterial species within biofilms. Additionally, the US-stimulated "exocytosis" by EMB-Hu can activate pro-inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell-like microbubbles with US-stimulated "exocytosis" mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms.

Ultrasound-responsive gallium protoporphyrin and oxygen loaded perfluoropentane nanodroplets for effective sonodynamic therapy of implant infections.

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.

Metabolic Modulation-Mediated Antibiotic and Immune Activation for Treatment of Chronic Lung Infections.

The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.

Self-Adaptive Antibiofilm Effect and Immune Regulation by Hollow Cu2MoS4 Nanospheres for Treatment of Implant Infections.

Implant infections are difficult to cure by traditional antibiotic therapy due to bacterial biofilm-induced antibiotic tolerance and impaired immune responses. To efficiently treat implant infections, therapeutic agents need to kill bacteria and regulate the inflammatory response of immune cells during the biofilm elimination process. Herein, multifunctional smart hollow Cu2MoS4 nanospheres (H-CMS NSs) with pH-responsive enzyme-like activities were prepared for self-adaptively eliminating biofilms and regulating the inflammation of macrophages in implant infections. During biofilm infection, the tissue microenvironment around implants is acidic. H-CMS NSs with oxidase (OXD)/peroxidase (POD)-like activities can catalyze reactive oxidative species (ROS) generation for directly killing bacteria and polarizing macrophages to a proinflammatory phenotype. Moreover, the POD-like activity and antibacterial property of H-CMS NSs can be further enhanced under ultrasound (US) irradiation. After the elimination of biofilms, the tissue microenvironment around implants shifts from acidic to neutral. H-CMS NSs show catalase (CAT)-like activity and eliminate excessive ROS, which polarizes macrophages to anti-inflammatory phenotype and promotes healing of infected tissue. This work provides a smart nanozyme with self-adaptive regulation of the antibiofilm activity and immune response by regulating ROS generation/elimination according to the different pathological microenvironments in implant infections during the different therapeutic stages.

Emerging nanosonosensitizers augment sonodynamic-mediated antimicrobial therapies.

With the widespread prevalence of drug-resistant pathogens, traditional antibiotics have limited effectiveness and do not yield the desired outcomes. Recently, alternative antibacterial therapies based on ultrasound (US) have been explored to overcome the crisis of bacterial pathogens. Antimicrobial sonodynamic therapy (aSDT) offers an excellent solution that relies on US irradiation to produce reactive oxygen species (ROS) and achieve antibiotic-free mediated antimicrobial effects. In addition, aSDT possesses the advantage of superior tissue penetrability of US compared to light irradiation, demonstrating great feasibility in treating deep infections. Although existing conventional sonosensitizers can produce ROS for antimicrobial activity, some limitations, such as low penetration rate, nonspecific distribution and poor ROS production under hypoxic conditions, result in suboptimal sterilization in aSDT. Recently, emerging nanosonosensitizers have enormous advantages as high-performance agents in aSDT, which overcome the deficiencies of conventional sonosensitizers as described above. Thus, nanosonosensitizer-mediated aSDT has a bright future for the management of bacterial infections. This review classifies the current available nanosonosensitizers and provides an overview of the mechanisms, biomedical applications, recent advances and perspectives of aSDT.

Amylase degradation enhanced NIR photothermal therapy and fluorescence imaging of bacterial biofilm infections.

Effective treatment of bacterial biofilm-related infections is a great challenge for the medical community. During the formation of biofilms, bacteria excrete extracellular polymeric substances (EPS), including polysaccharides, proteins, nucleic acids, etc., to encapsulate themselves and form a "fort-like" structure, which greatly reduces the efficiency of therapeutic agents. Herein, we prepared a nanoagent (MnO2-amylase-PEG-ICG nanosheets, MAPI NSs) with biofilm degradation capability for efficient photothermal therapy and fluorescence imaging of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections. MAPI NSs were constructed by sequentially modifying α-amylase, polyethylene glycol (PEG), and indocyanine green (ICG) on manganese dioxide nanosheets (MnO2 NSs). Experimental results exhibited that MAPI NSs could accumulate in infected tissues after intravenous injection, degrade in the acidic biofilm microenvironment, and release the loaded ICG for near-infrared (NIR) fluorescence imaging of the infected tissues. Importantly, MAPI NSs could efficiently eliminate MRSA biofilm infections in mice by α-amylase enhanced photothermal therapy. In addition, MAPI NSs exhibited neglectable toxicity towards mice. Given the superior properties of MAPI NSs, the enzyme-degradation enhanced therapeutic strategy presented in this work offers a promising solution for effectively combating biofilm infectious diseases.

Nanotherapeutics with immunoregulatory functions for the treatment of bacterial infection.

The advent of drug-resistant pathogens results in the occurrence of stubborn bacterial infections that cannot be treated with traditional antibiotics. Antibacterial immunotherapy by reviving or activating the body's immune system to eliminate pathogenic bacteria has confirmed promising therapeutic strategies in controlling bacterial infections. Subsequent studies found that antimicrobial immunotherapy has its own benefits and limitations, such as avoiding recurrence of infection and autoimmunity-induced side effects. Current studies indicate that the various antibacterial therapeutic strategies inducing immune regulation can achieve superior therapeutic efficacy compared with monotherapy alone. Therefore, summarizing the recent advances in nanomedicine with immunomodulatory functions for combating bacterial infections is necessary. Herein, we briefly introduce the crisis caused by drug-resistant bacteria and the opportunity for antibacterial immunotherapy. Then, immune-involved multimodal antibacterial therapy for the treatment of infectious diseases was systematically summarized. Finally, the prospects and challenges of immune-involved combinational therapy are discussed.

Recent advances in Prussian blue-based photothermal therapy in cancer treatment.

Malignant tumours are a serious threat to human health. Traditional chemotherapy has achieved breakthrough improvements but also has significant detrimental effects, such as the development of drug resistance, immunosuppression, and even systemic toxicity. Photothermal therapy (PTT) is an emerging cancer therapy. Under light irradiation, the phototherapeutic agent converts optical energy into thermal energy and induces the hyperthermic death of target cells. To date, numerous photothermal agents have been developed. Prussian blue (PB) nanoparticles are among the most promising photothermal agents due to their excellent physicochemical properties, including photoacoustic and magnetic resonance imaging properties, photothermal conversion performance, and enzyme-like activity. By the construction of suitably designed PB-based nanotherapeutics, enhanced photothermal performance, targeting ability, multimodal therapy, and imaging-guided cancer therapy can be effectively and feasibly achieved. In this review, the recent advances in PB-based photothermal combinatorial therapy and imaging-guided cancer therapy are comprehensively summarized. Finally, the potential obstacles of future research and clinical translation are discussed.

Ultrasound-responsive catalytic microbubbles enhance biofilm elimination and immune activation to treat chronic lung infections.

Efficient treatment of chronic lung infections caused by Pseudomonas aeruginosa biofilms is a great challenge because of drug tolerance and immune evasion issues. Here, we develop ultrasound-responsive catalytic microbubbles with biofilm elimination and immune activation properties to combat chronic lung infection induced by P. aeruginosa biofilms. In these microbubbles, piperacillin and Fe3O4 nanoparticles form a drug-loaded shell surrounding the air core. Under ultrasound stimulation, the microbubbles can physically disrupt the structure of biofilms and enhance the penetration of both Fe3O4 nanoparticles and piperacillin into the biofilm. Then, Fe3O4 nanoparticles chemically degrade the biofilm matrix and kill the bacteria with the assistance of piperacillin. Fe3O4 nanoparticles can activate the immune response for biofilm elimination by polarizing macrophages into a pro-inflammatory phenotype. These ultrasound-responsive catalytic microbubbles efficiently treat chronic lung infections in a mouse model by combining physical/chemical/antibiotic biofilm elimination and immune activation, thus providing a promising strategy for combating bacterial biofilm infections.

Endogenous/Exogenous Nanovaccines Synergistically Enhance Dendritic Cell-Mediated Tumor Immunotherapy.

Traditional dendritic cell (DC)-mediated immunotherapy is usually suppressed by weak immunogenicity in tumors and generally leads to unsatisfactory outcomes. Synergistic exogenous/endogenous immunogenic activation can provide an alternative strategy for evoking a robust immune response by promoting DC activation. Herein, Ti3 C2 MXene-based nanoplatforms (termed MXP) are prepared with high-efficiency near-infrared photothermal conversion and immunocompetent loading capacity to form endogenous/exogenous nanovaccines. Specifically, the immunogenic cell death of tumor cells induced by the photothermal effects of the MXP can generate endogenous danger signals and antigens release to boost vaccination for DC maturation and antigen cross-presentation. In addition, MXP can deliver model antigen ovalbumin (OVA) and agonists (CpG-ODN) as an exogenous nanovaccine (MXP@OC), which further enhances DC activation. Importantly, the synergistic strategy of photothermal therapy and DC-mediated immunotherapy by MXP significantly eradicates tumors and enhances adaptive immunity. Hence, the present work provides a two-pronged strategy for improving immunogenicity and killing tumor cells to achieve a favorable outcome in tumor patients.

Photocatalytic Cu2WS4 Nanocrystals for Efficient Bacterial Killing and Biofilm Disruption.

Background: Bacterial biofilm-related wound infections threaten human health due to the lack of efficient treatments. Therefore, developing a novel strategy for wound infection care is urgently needed. Methods: Cube-shaped Cu2WS4 nanocrystals (CWSNs) were successfully prepared via a microwave-assisted method. CWSNs, as photocatalysts, were first studied by using fluorescence spectroscopy for their ability to generate reactive oxygen species (ROS). The antibacterial and biofilm inhibition abilities of CWSNs were determined in vitro by using Staphylococcus aureus (S. aureus) as the model bacterium. Moreover, a CWSN gel was prepared and applied to treat S. aureus-infected wounds in mice. The toxicity of the CWSNs was evaluated through in vitro cell and in vivo animal experiments. Results: Studies on the properties of the CWSNs demonstrated that these nanomaterials can catalyze the generation of hydroxyl radicals (•OH) without the addition of H2O2 after visible-light irradiation, indicating their photocatalytic ability. Moreover, the in vitro experimental results showed that the CWSNs not only adhered to the surfaces of S. aureus to kill the bacteria, but also inhibited S. aureus biofilm formation. The in vivo study showed that the CWSN gel produced excellent antibacterial effects against S. aureus infected wounds in mice and effectively promoted wound healing. Furthermore, toxicity tests showed that the CWSNs have negligible toxicity in vitro and in vivo. Conclusion: This work provides a potential photocatalytic antibacterial nanoagent for efficient bacterial killing, inhibition of biofilms growth and wound infection treatment.

Potentiating hypoxic microenvironment for antibiotic activation by photodynamic therapy to combat bacterial biofilm infections.

Traditional antibiotic treatment has limited efficacy for the drug-tolerant bacteria present in biofilms because of their unique metabolic conditions in the biofilm infection microenvironment. Modulating the biofilm infection microenvironment may influence the metabolic state of the bacteria and provide alternative therapeutic routes. In this study, photodynamic therapy is used not only to eradicate methicillin-resistant Staphylococcus aureus biofilms in the normoxic condition, but also to potentiate the hypoxic microenvironment, which induces the anaerobic metabolism of methicillin-resistant Staphylococcus aureus and activates the antibacterial activity of metronidazole. Moreover, the photodynamic therapy-activated chemotherapy can polarize the macrophages to a M2-like phenotype and promote the repair of the biofilm infected wounds in mice. This biofilm infection microenvironment modulation strategy, whereby the hypoxic microenvironment is potentiated to synergize photodynamic therapy with chemotherapy, provides an alternative pathway for efficient treatment of biofilm-associated infections.

NIR-responsive MoS2-Cu2WS4 nanosheets for catalytic/photothermal therapy of methicillin-resistant Staphylococcus aureus infections.

The extensive usage of antibiotics causes the rapid evolution of drug-resistant bacteria, which seriously threaten human health. Thus, efficient strategies for treating drug-resistant bacterial infections are urgently needed. Herein, MoS2-Cu2WS4 nanosheets (MS-CWS NSs) are prepared as a near-infrared (NIR) light responsive nanozyme to effectively combat methicillin-resistant Staphylococcus aureus (MRSA) infections by catalytic/photothermal effects. By integrating oxidase (OXD)- and peroxidase (POD)-mimic catalytic activity, MS-CWS NSs have the ability to inactivate MRSA without the addition of H2O2. Moreover, the reactive oxygen species (ROS) produced from MS-CWS NSs are further enhanced by NIR light irradiation, which remarkably causes the death of MRSA. MS-CWS NSs show 4.4 log (99.996%) bacterial inactivation efficiency of MRSA in vitro under NIR light irradiation (0.8 W cm-2, 5 min). In an MRSA infected wound mouse model, MS-CWS NSs inactivate the MRSA by more than 5.2 log (>99.999%) and effectively promote wound healing. This work provides an NIR-responsive 2D nanozyme for efficient treatment of MRSA infections.

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

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

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.