Synergistic Treatment Research Articles

Enhancing Cancer Treatment Through Combined Approaches: Photodynamic Therapy in Concert with Other Modalities

This review explores the role of photodynamic therapy (PDT) as an adjunctive treatment for cancers, with a focus on its potential to enhance the effects of established therapies like chemotherapy, surgery, and radiotherapy. Given the limitations of conventional cancer treatments, PDT’s ability to improve therapeutic outcomes through combination strategies is examined. In cancers such as lung, breast, cholangiocarcinoma, and cervical, PDT shows promise in enhancing response rates, reducing recurrence, and minimizing adverse effects when used alongside standard modalities. This study highlights current findings on PDT’s mechanisms in complementing chemotherapy, augmenting surgical precision, and enhancing radiotherapeutic effects, thus offering a multi-faceted approach to cancer treatment. Additionally, insights into the clinical application of PDT in these cancers emphasize its potential for reducing tumor resistance and supporting more effective, personalized care. By providing an overview of PDT’s synergistic applications across diverse cancer types, this review underscores its emerging significance in oncology as a tool to address traditional treatment limitations. Ultimately, this review aims to inform and inspire researchers and clinicians seeking to refine and innovate cancer therapy strategies through PDT integration, contributing to the advancement of more effective, synergistic cancer treatments.

Living Therapeutics for Synergistic Hydrogen-Photothermal Cancer Treatment by Photosynthetic Bacteria.

Hydrogen gas (H2) therapy, recognized for its inherent biosafety, holds significant promise as an anti-cancer strategy. However, the efficacy of H2 treatment modalities is compromised by their reliance on systemic gas administration or chemical reactions generation, which suffers from low efficiency, poor targeting, and suboptimal utilization. In this study, living therapeutics are employed using photosynthetic bacteria Rhodobacter sphaeroides for in situ H2 production combined with near-infrared (NIR) mediated photothermal therapy. Living R. sphaeroides exhibits strong absorption in the NIR spectrum, effectively converting light energy into thermal energy while concurrently generating H2. This dual functionality facilitates the targeted induction of tumor cell death and substantially reduces collateral damage to adjacent normal tissues. The findings reveal that integrating hydrogen therapy with photothermal effects, mediated through photosynthetic bacteria, provides a robust, dual-modality approach that enhances the overall efficacy of tumor treatments. This living therapeutic strategy not only leverages the therapeutic potential of both hydrogen and photothermal therapeutic modalities but also protects healthy tissues, marking a significant advancement in cancer therapy techniques.

A multifunctional cascade gas-nanoreactor with MnO2 as a gatekeeper to enhance starvation therapy and provoke antitumor immune response

Glucose oxidase (GOx)-mediated starvation therapy is an effective tumor treatment that blocks energy and activates the immune response. However, the insufficient tumor immunogenicity and immunosuppressive tumor microenvironment (TME) limited its therapeutic efficacy. To address this, we have designed a multifunctional cascade gas-nanoreactor with a MnO2 coating, which serves as an out gatekeeper to encapsulate both GOx and a carbon monoxide (CO) donor (denoted as GCM). Due to the protective effect of MnO2 coating, GCM maintains better stability in normal physiological environments, enhancing the catalytic activity of GOx and minimizing toxic side effects. Upon accumulation in the tumor, the degradation of MnO2 coating exposes the GOx enzyme, thereby initiating a cascade catalysis reaction to generate hydrogen peroxide (H2O2) and release CO in the hypoxic conditions. Additionally, the released Mn2+ reacts with H2O2 to generate toxic hydroxyl radical (•OH) as chemodynamic therapy (CDT). The synergistic treatments of starvation therapy, CO gas therapy and CDT effectively kill cancer cells and amplify immunogenic cell death (ICD), maturing DC cells and activating anti-tumor immune response. Furthermore, the released CO increases M1 macrophages infiltration and reduces myeloid-derived suppressor cells (MDSCs) infiltration, thus reversing the immunosuppressive TME. This multifunctional gas-nanoreactor provides a strategy for CO gas generation to trigger a robust anti-tumor immune response and has the potential for clinical application in cancer immunotherapy. Statement of significanceA multifunctional cascade gas-nanoreactor with a MnO2 gatekeeper was developed to perform synergistic treatments involving starvation therapy, CO gas therapy and chemodynamic therapy (CDT) for tumor elimination. The MnO2 gatekeeper enhanced the catalytic activity of GOx within the nanoreactor by generating oxygen, thereby minimizing toxic side effects after intravenous injection. The gas-nanoreactor amplified ICD through synergistic treatments to mature DC cells and activate anti-tumor immune response. Furthermore, the released CO could reverse the immunosuppression of the TME to enhance cancer immunotherapy. The combination strategy utilizing the gas-nanoreactor demonstrates clinical potential for facilitating cancer immunotherapy.

Wireless power supply near-infrared light drug-loaded microneedle system for the treatment of linear skin wounds

The healing of linear skin wounds is a complex biological process, and traditional treatment methods have certain limitations. This study proposes a wireless power supply near-infrared light drug-loaded microneedle system (NIR-LED-NG-R1-MN), which utilizes microneedles (MNs) to achieve targeted delivery of the active component of traditional Chinese medicine, Notoginsenoside R1 (NG-R1), and combines the biological regulatory effect of near-infrared light (NIR) to achieve efficient synergistic treatment for linear skin wounds. Experimental results show that the device can significantly promote the wound closure rate and reduce the levels of inflammatory factors and the risk of scar formation. By comparing the wound repair conditions of different treatment groups, it was found that the group treated with the NIR-LED-NG-R1-MN patch for NG-R1 and NIR synergistic treatment (MN@NG-R1@LED group) showed superior wound repair effects compared to other groups, thus confirming the synergistic therapeutic advantages of NG-R1 and NIR in skin wound healing. In addition, the application of wireless power supply technology used in this system eliminates the dependence on external power sources, enhancing the convenience of treatment. This study clearly demonstrates that the NIR-LED-NG-R1-MN has the potential to become a new clinical method for the treatment of linear skin wound healing.

Effect of cellulase-assisted cold isostatic pressure extraction on the characteristics and functional properties of polyphenol extracts from camellia sinensis seeds

In this experiment, polyphenolic substances were extracted from Camellia sinensis seeds (CSS) using a synergistic treatment of cold isostatic pressure (CIP) and cellulase. The effects of pressure, treatment time, and cellulase addition on the experiment were investigated. And the optimal extraction conditions were established by single factor experiment and Box-benhken experiments: the pressure applied by CIP was 408.649 MPa, the treatment time was 10.995 min, and the cellulase addition was 4.098 %. The polyphenols in the extract were characterized and quantified using LC-MS/MS. By comparing the different treatments, it was found that the synergistic treatment of CIP and cellulase resulted in a higher extraction yield. FTIR, XRD and SEM mapping showed that CIP synergistic pretreatment with cellulase was able to disrupt the microstructure of the plant and promote the influx of the active ingredients into solution. Finally, the activity of the extracts was detected by using in vitro antioxidant experiments and RAW264.7 cellular anti-inflammatory experiments, which indicated that CIP and cellulase synergistically treated polyphenol extracts had high antioxidant and anti-inflammatory capacity. This experiment provides a new pretreatment method for extracting active substances from CSS.

Effective Antitumor Synergistic Treatment with Fiber-Photothermal Therapy and Heat Shock Protein Inhibitors.

Effective treatment of malignant tumors remains a thorny issue in current medicine. As a new type of anticancer strategy, photothermal therapy (PTT) has attracted tremendous attention due to its favorable therapeutic effectiveness, high spatial-temporal controllability, and low occurrence of side effects. However, the efficacy of PTT is significantly reduced due to the limited penetration of light and heat-induced overexpression of heat shock protein (Hsp). Herein, we propose an antitumor synergistic therapy that combines fiber-optic PTT and Hsp inhibitors. A rare-earth-doped optical fiber was used as the PTT actuator, and the Hsp inhibitor AT533 was loaded on the fiber surface by use of a hydrogel layer. PTT fibers can be guided to reach tumor lesions directly without being subject to the light penetration limit. The Hsp inhibitor can be released upon the softening of the hydrogel layer under photoheating to deactivate Hsp in the tumor and thus reduce the resistance of the tumor to PTT. This synergistic treatment enhanced the effect of PTT and successfully eradicated tumors in colorectal cancer (CRC) xenograft mouse models, providing a feasible way to realize antitumor and antirecurrence treatment. More importantly, the success of the synergistic treatment of PTT and Hsp inhibition opens new avenues for the development of multimodal and multitype synergistic fiber-optic treatments, which offer pronounced enhancement of therapeutic effectiveness for treating cancer.

Macrophage membrane-functionalized manganese dioxide nanomedicine for synergistic treatment of atherosclerosis by mitigating inflammatory storms and promoting cholesterol efflux

Atherosclerosis (AS) poses a significant threat to human life and health. However, conventional antiatherogenic medications exhibit insufficient targeting precision and restricted therapeutic effectiveness. Moreover, during the progression of AS, macrophages undergo polarization toward the proinflammatory M1 phenotype and generate reactive oxygen species (ROS) to accelerate the occurrence of inflammatory storms, and ingest excess lipids to form foam cells by inhibiting cholesterol efflux. In our study, we developed a macrophage membrane-functionalized hollow mesoporous manganese dioxide nanomedicine (Col@HMnO2-MM). This nanomedicine has the ability to evade immune cell phagocytosis, enables prolonged circulation within the body, targets the inflammatory site of AS for effective drug release, and alleviates the inflammatory storm at the AS site by eliminating ROS. Furthermore, Col@HMnO2-MM has the ability to generate oxygen autonomously by breaking down surplus hydrogen peroxide generated at the inflammatory AS site, thereby reducing the hypoxic microenvironment of the plaque by downregulating hypoxia-inducible factor (HIF-1α), which in turn enhances cholesterol efflux to inhibit foam cell formation. In an APOE−/− mouse model, Col@HMnO2-MM significantly reduced inflammatory factor levels, lipid storage, and plaque formation without significant long-term toxicity. In summary, this synergistic treatment significantly improved the effectiveness of nanomedicine and may offer a novel strategy for precise AS therapy.

A Machine Learning-Optimized System for Pulsatile, Photo- and Chemotherapeutic Treatment Using Near-Infrared Responsive MoS2-Based Microparticles in a Breast Cancer Model.

Multimodal cancer therapies are often required for progressive cancers due to the high persistence and mortality of the disease and the negative systemic side effects of traditional therapeutic methods. Thus, the development of less invasive modalities for recurring treatment cycles is of clinical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation. The system is composed of poly(caprolactone) microparticles of 200 μm size containing molybdenum disulfide (MoS2) nanosheets as the photothermal agent and hydrophilic doxorubicin or hydrophobic violacein, as model drugs. Upon irradiation, the nanosheets heat up to ≥50 °C leading to polymer softening and release of the drug. MoS2 nanosheets exhibit high photothermal conversion efficiency and require low-power laser irradiation. A machine learning algorithm was applied to acquire the optimal laser operation conditions. In a mouse subcutaneous model of 4T1 triple-negative breast cancer, 25 microparticles were intratumorally administered, and after 3-cycle laser treatment, the system conferred synergistic phototherapeutic and chemotherapeutic effects. Our on-demand, pulsatile synergistic treatment resulted in increased median survival up to 39 days post start of treatment compared to untreated mice, with complete eradication of the tumors at the primary site. Such a system is therapeutically relevant for patients in need of recurring cycles of treatment on small tumors, since it provides precise localization and low invasiveness and is not cross-resistant with other treatments.

Compact Molecular Conformation of Prodrugs Enhances Photocleaving Performance for Tumor Vascular Growth Inhibition.

Highly spatiotemporal-resolved photomodulation demonstrates promise for investigating key biological events in vivo and in vitro, such as cell signaling pathways, neuromodulation, and tumor treatment without side effects. However, enhancing the performance of photomodulation tools remains challenging due to the limitations of the physicochemical properties of the photoactive molecules. Here, a compact, stable intramolecular π-πstacking conformation forming between the target molecule (naproxen) and the perylene-based photoremovable protecting group is discovered to confine the motion of the photolabile bond and then enhance the photocleavage quantum yield. In conjunction with a red-absorbing photosensitizer, the photocleavage wavelength is extended to the red region via triplet-triplet annihilation. In particular, the triplet lifetime of the prodrug can be extended via the linked steric hindrance to improve the conversion yield via TTA. Using the new photomodulation tool, it is precisely photoreleased cyclooxygenase-2 inhibitors for tumor vascular growth suppression in vivo. In combination with cisplatin, over 90% efficient inhibition of malignant breast tumors is observed via the synergistic tumor treatment strategy. These findings provide a new concept for the rational design of efficient photocleavage and have implications for photomodulating cell signaling pathways in tumor therapy, as well as laying a solid foundation for the development of phototherapeutic approaches.

Tannic Acid-Based Biomimetic Nanomedicine with Pathological Reactive Oxygen Species-Responsive Cargo Release for Relieving Inflammation in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic disease characterized by immune cell infiltration and cartilage damage. The local lesion of RA shows severe oxidative stress and proinflammatory cytokine secretion. For drug therapy, the efficacy of agents, such as methotrexate (MTX), may be greatly limited, resulting from the low bioavailability, immune clearance, and toxic side effects. A nanocarrier (TA-PBA NPs) was developed with anti-inflammatory and antioxidant activities, combined with MTX to prepare nanomedicine (MTX NPs) for synergistic treatment of RA. Moreover, inspired by the biological functions homing to inflammation lesion of macrophages, the biomimetic nanomedicine camouflaged with macrophage membrane (MM@MTX NPs) was constructed. TA-PBA NPs could timely promote MTX release in response to the overaccumulated ROS to exhibit high anti-inflammatory and antioxidant activities for alleviating RA progression. The experimental results confirmed that MM@MTX NPs could significantly reduce the secretion of proinflammatory cytokines (TNF-α) while significantly increasing the typical anti-inflammatory cytokines (IL-10), promote the phenotype transformation of macrophages from M1 to M2, and up-regulate the Nrf2-keap1 pathway-related proteins (HO-1 and NRF2) to positively regulate the local inflammation for effectively inhibiting RA development. Thus, MM@MTX NPs represent a possible candidate as a safe and efficient nanotherapy platform for RA management.

Blautia coccoides and its metabolic products enhance the efficacy of bladder cancer immunotherapy by promoting CD8+ T cell infiltration

BackgroundImmune checkpoint inhibitors (ICIs) have emerged as a novel and effective treatment strategy, yet their effectiveness is limited to a subset of patients. The gut microbiota, recognized as a promising anticancer adjuvant, is being increasingly suggested to augment the efficacy of ICIs. Despite this, the causal link between the gut microbiota and the success of immunotherapy is not well understood. This gap in knowledge has driven us to identify beneficial microbiota and explore the underlying molecular mechanisms.MethodsThrough 16S rDNA sequencing, we identified distinct gut microbiota in patients undergoing treatment with ICIs. Following this, we assessed the impact of probiotics on anti-PD-1 therapy in bladder cancer using mouse models, employing a multi-omics strategy. Subsequently, we uncovered the mechanisms through which Blautia-produced metabolites enhance antitumor immunity, utilizing untargeted metabolomics and a range of molecular biology techniques.ResultsIn our research, the LEfSe analysis revealed a significant enrichment of the Blautia genus in the gut microbiota of patients who responded to immunotherapy. We discovered that the external addition of Blautia coccoides hampers tumor growth in a bladder cancer mouse model by enhancing the infiltration of CD8+ T cells within the tumor microenvironment (TME). Further investigations through untargeted metabolomics and molecular biology experiments showed that oral administration of Blautia coccoides elevated trigonelline levels. This, in turn, suppresses the β-catenin expression both in vitro and in vivo, thereby augmenting the cancer-killing activity of CD8+ T cells.ConclusionsThis research provided valuable insights into enhancing the efficacy of PD-1 inhibitors in clinical settings. It was suggested that applying Blautia coccoides and its metabolic product, trigonelline, could serve as a synergistic treatment method with PD-1 inhibitors in clinical applications.Graphical

Synergistic organic manure treatment with Al/Fe/Ca-based fluoride-fixing agents promote soil formation and utilization of phosphate flotation tailings

Soil utilization of phosphate ore flotation tailings (PTs) was achieved using F-fixing agents combined with organic manure treatment to address issues related to inefficient stabilization of P-F, heavy metal solidification/stabilization, poor physicochemical properties, and ecological disruption. The formulation for PTs soil utilization included 1.75 % polyaluminum sulfate (PAS), 1.75 % FeSO4, and 0.25 % CaO, with PTs content at ≥86.75 %. This approach enhanced water retention and improved nutrient and biochemical conditions. Various nutrient indexes met general planting soil requirements: organic matter 24.93 g/kg, available K 252.26 mg/kg, available Ca 2048.67 mg/kg, available Mg 246.13 mg/kg, and ammonia-nitrogen 42.47 mg/kg. The water-soluble P content of PTs-based soil decreased to 6.96 mg/kg, while available P increased to 677.99 mg/kg. Mn leaching toxicity was less than 0.016 mg/L, with a stabilization efficiency of 96.86 %. Water-soluble F in PTs-based soil was reduced to 11.133 mg/kg. This study maximized phosphorus resource utilization and prevented the migration of water-soluble P, F, and Mn to the surrounding environment. Potting experiments showed PTs-based soil was more effective than red soil and PTs-based raw materials in cabbage plantation, achieving a maximum seedling emergence rate of 98.33 %. Microbial diversity increased, and community structure improved in 40-day soil formation experiments, with PTs-based soils developing microbial communities involved in carbon and nitrogen cycling, enhancing resistance to external environmental disturbances, and promoting ecological utilization. These findings offer practical insights into the ecological utilization of large quantities of PTs and present a cost-effective approach for producing planting soils or ecological mulches from similar solid wastes.

Plasmonic Supramolecular Nanozyme-Based Bio-Cockleburs for Synergistic Therapy of Infected Diabetic Wounds.

Diabetic wounds are a major devastating complication of diabetes due to hyperglycemia, bacterial invasion, and persistent inflammation, and the current antibiotic treatments can lead to the emergence of multidrug-resistant bacteria. Herein, a bimetallic nanozyme-based biomimetic bio-cocklebur (GNR@CeO2@GNPs) is designed and synthesized for diabetic wound management by depositing spiky ceria (CeO2) shells and gold nanoparticles (GNPs) on a gold nanorod (GNR) nanoantenna. The plasmonic-enhanced nanozyme catalysis and self-cascade reaction properties simultaneously boost the two-step enzyme-mimicking catalytic activity of GNR@CeO2@GNPs, leading to a significant improvement in overall therapeutic efficacy rather than mere additive effects. Under the glucose activation and 808nm laser irradiation, GNR@CeO2@GNPs material captures photons and promotes the transfer of hot electrons from GNR and GNPs into CeO2, realizing a "butterfly effect" of consuming local glucose, overcoming the limited antibacterial efficiency of an individual PTT modality, and providing substantial reactive oxygen species. In vitro and in vivo experiments demonstrate the material's exceptional antibacterial and antibiofilm properties against Gram-negative and Gram-positive bacteria, which can reduce inflammation, promote collagen deposition, and facilitate angiogenesis, thereby accelerating wound healing. This study provides a promising new strategy to develop plasmonic-enhanced nanozymes with a catalytic cascade mode for the antibiotic-free synergistic treatment of infected diabetic wounds.

Synergy between bio-control agents to trigger the defensive responses against Rhizoctonia root rot and enhance the growth, yield, and physiological and anatomical traits of pea plants

AbstractRhizoctonia solani (Rs) is the fungus that causes the primary and deadly disease that attacks pea plants throughout the cool growing season. It causes seed rot, damping off, and pea root rot diseases. The current study used arbuscular mycorrhizal fungi; Rhizoglomus clarum, Gigaspora margarita, Rhizophagus irregularis and Funneliformis mosseae (AMF), Pseudomonas fluorescens HE21 (Pf), and Trichoderma harzianum HL9 (TH) singly or in combination to suppress Rhizoctonia root rot of pea in a greenhouse. Using the in vitro dual culture assay, TH and Pf inhibited the radial growth of the Rs by 73.3 and 60.0%, respectively. The results of greenhouse experiments showed that all treatments significantly decreased the percentages of pre- and post-emergence damping while significantly increasing the number of surviving plants, particularly in the dual and triple combination treatments. Furthermore, all treatments improved yield and seed quality in addition to plant growth, total phenol content and antioxidant enzyme activity. There were also noted modifications to the treated plants’ anatomical, physiological, and distinctive features. The synergistic triple treatment consisting of M, TH, and Pf achieved the maximum reduction of disease severity (78.5%) compared to the untreated control treatment. As a result of the synergistic triple treatment due to their effectiveness and eco-safety, we recommend using the synergistic triple by M + Pf + TH to manage the root rot disease in peas caused by Rs and to enhance the crop’s growth, yield, and seed quality.

Enzyme-mediated multifunctional self-healing lysozyme hydrogel for synergistic treatment of chronic diabetic wounds

Self-healing hydrogels have attracted significant attention in chronic diabetic wound healing due to their potential to minimize the risk of secondary infections caused by joint movement or dressing rupture. Herein, a multifunctional self-healing hydrogel mediated utilizing an enzyme-triggered cascade reaction based on dynamic imine bonds was designed. The hydrogel employs three enzymes: lysozyme (LYZ), glucose oxidase (GOx), and catalase (CAT), as building blocks. GOx catalyzes the conversion of glucose and 1-thio-β-d-glucose (β-GlcSH) into hydrogen peroxide (H2O2), gluconic acid (GA), and hydrogen sulfide (H2S). Subsequently, CAT eliminates H2O2, protecting the imine bonds from oxidative damage. The acidic environment created by GA decreases the pH and regulates the crosslinking density of imine bonds, enhancing the self-healing capability and porosity of the hydrogel. This feature enables the sustained release of the drug rosuvastatin calcium (RCa) to promote endothelial cell migration and vascular regeneration. Combined with the antioxidative and anti-inflammatory effects of released H2S gas and the antibacterial properties of lysozyme, this hydrogel exhibits promising therapeutic efficacy for the synergistic treatment of chronic diabetic wounds.

Multi‐Enzyme Mimetic MoCu Dual‐Atom Nanozyme Triggering Oxidative Stress Cascade Amplification for High‐Efficiency Synergistic Cancer Therapy

AbstractSingle‐atom nanozymes (SAzymes) with ultrahigh atom utilization efficiency have been extensively applied in reactive oxygen species (ROS)‐mediated cancer therapy. However, the high energy barriers of reaction intermediates on single‐atom sites and the overexpressed antioxidants in the tumor microenvironment restrict the amplification of tumor oxidative stress, resulting in unsatisfactory therapeutic efficacy. Herein, we report a multi‐enzyme mimetic MoCu dual‐atom nanozyme (MoCu DAzyme) with various catalytic active sites, which exhibits peroxidase, oxidase, glutathione (GSH) oxidase, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mimicking activities. Compared with Mo SAzyme, the introduction of Cu atoms, formation of dual‐atom sites, and synergetic catalytic effects among various active sites enhance substrate adsorption and reduce the energy barrier, thereby endowing MoCu DAzyme with stronger catalytic activities. Benefiting from the above enzyme‐like activities, MoCu DAzyme can not only generate multiple ROS, but also deplete GSH and block its regeneration to trigger the cascade amplification of oxidative stress. Additionally, the strong optical absorption in the near‐infrared II bio‐window endows MoCu DAzyme with remarkable photothermal conversion performance. Consequently, MoCu DAzyme achieves high‐efficiency synergistic cancer treatment incorporating collaborative catalytic therapy and photothermal therapy. This work will advance the therapeutic applications of DAzymes and provide valuable insights for nanocatalytic cancer therapy.

H2O2 Self-Supplying CaO2 Nanoplatform Induces Ca2+ Overload Combined with Chemodynamic Therapy to Enhance Cancer Immunotherapy.

Integrating chemodynamic therapy (CDT) with Ca2+ overload offers a potent strategy for enhancing cancer immunotherapy. However, the effectiveness of this approach is significantly constrained by the scarce availability of H2O2 in solid tumors. Here, we engineered a nanoplatform based on CaO2 nanoparticles (NPs) capable of encapsulating curcumin (CUR) and self-supplying H2O2 for synergistic CDT-augmented antitumor immunotherapy (CaO2@CUR@ZIF-Cu, denoted as CCZC). In the acidic tumor microenvironment, CCZC disintegrated to release CUR and copper(II) ions (Cu2+), revealing the core CaO2 NPs. CDT was amplified by escalating hydroxyl radical (•OH) production through a Fenton-like reaction mediated by H2O2 from the hydrolysis of CaO2 NPs. Ca2+ sourced from CaO2 NPs and CUR, an initiator of Ca2+ overload, induced Ca2+ overload in tumor cells, thereby promoting apoptosis. Subsequently, apoptotic tumor cells released tumor-associated antigens and pro-inflammatory cytokines, triggering adaptive immune responses and enhancing antitumor immunotherapy effects. In vivo experiments demonstrated that the intratumoral administration of CCZC displayed significant inhibitory effects, with an inhibition rate of up to 78% on B16-OVA-tumor-bearing mice compared to untreated. Moreover, an elevated proportion of mature dendritic cells were observed in the tumor-draining lymph nodes, along with an increase in cytotoxic T lymphocytes in the spleen. These findings suggest that our engineered nanoplatform effectively curtailed tumor growth via enhanced cancer immunotherapy by synergizing Ca2+ overload and CDT, proposing a novel strategy for synergistic cancer treatment.

A Self-Assembled Transdermal Nanomedicines Incorporating Pendant Disulfides for Non-Invasive, Synergistic Treatment of Melanoma.

Transdermal drug delivery system (TDDS) offers lower systemic toxicity and good patient compliance, making it a promising treatment option for skin-related cancers. However, physiological barriers in the skin frequently impede the therapeutic efficiency of TDDS. To address this, a unique self-assembled TDDS that incorporates disulfide pendant groups (termed Sup-TDDS) is presented. It is formulated with dithiolane-containing lipoic acid (LA), photosensitizers Ce6, and chemotherapeutic agents trametinib. Pendant disulfide moieties on Sup-TDDS facilitate thiol-disulfide exchange reactions with exofacial thiols on cell surfaces, thus enhancing stratum corneum penetration. In contrast to intravenous injection, topical administration of Sup-TDDS can penetrate deeper into the skin (> 500 µm) and promote drug accumulation in subcutaneous tumors. In a B16F10-bearing mouse model, Sup-TDDS treatment demonstrates significant anti-tumor effects in primary and recurrent melanoma, benefiting from the synergistic effects of Ce6 and trametinib. These results underscore that Sup-TDDS's transdermal properties allow non-invasive melanoma therapy, implying the potential of nanodrugs containing pendant disulfides for transdermal treatment of skin illnesses.

Ozone disinfection of waterborne pathogens: A review of mechanisms, applications, and challenges.

Water serves as a critical vector for the transmission of pathogenic microorganisms, playing a pivotal role in the emergence and propagation of numerous diseases. Ozone (O3) disinfection technology offers promising potential for mitigating the spread of these pathogens in aquatic environments. However, previous studies have only focused on the inactivated effect of O3 on a single pathogenic microorganism, lacking a comprehensive comparative analysis of various influencing factors and different types of pathogens, while the cost-effectiveness of O3 technology has not been mentioned. This review synthesized the migration characteristics of various pathogenic microorganisms in water bodies and examined the properties, mechanisms, and influencing factors of O3 inactivation. It evaluated the efficacy of O3 against diverse pathogens, namely bacteria, viruses, protozoa, and fungi, and provided a comparative analysis of their sensitivities to O3. The formation and impact of harmful disinfection by-products (DBPs) during the O3 inactivation process were assessed, alongside an analysis of the cost-effectiveness of this method. Additionally, potential synergistic treatment processes involving O3 were proposed. Based on these findings, recommendations were made for optimizing the utilization of O3 in water inactivation in order to formulate better inactivation strategies in the post-pandemic eras.

Cell membrane camouflaged Cu-doped mesoporous polydopamine for combined CT/PTT/CDT synergistic treatment of breast cancer

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer.