RESUMO
To the best of our knowledge, the output performance of a self-Q-switched Tm:YAP laser has been controlled by adjusting the cavity length for the first time. By using a concise concave-flat cavity, a pulsed laser emitting at 1993â nm is produced without any additional modulation device. Under a stable self-Q-switched mode, the maximum average output power of 9.76â W is achieved from the laser when the incident pump power is 28.78â W, corresponding to a slope efficiency of 36.9% and an optical-to-optical conversion efficacy of 33.9%. Also, the narrowest pulse width of 485â ns at 48.97â kHz is obtained from the laser with a single pulse energy of 199.3â µJ. As far as we know, this laser has the highest average power and narrowest pulse width compared to other self-Q-switched Tm:YAP lasers.
RESUMO
The interlayer strategy has emerged as an effective approach for modulating the interfacial polymerization process and improving the permeability and selectivity of polyamide membranes. However, the underlying mechanisms by which charged interlayers influence the interfacial polymerization process remain inadequately understood. In this study, we utilized two distinct charged cellulose nanofibers, namely, carboxylated cellulose (â-CNF) and quaternized cellulose ([Formula: see text]-CNF), as interlayers to regulate the interfacial polymerization process. Through simulation results, isothermal titration calorimetry (ITC) and UV tests, we demonstrated that the [Formula: see text]-CNF interlayer, which possesses stronger hydration capability and better piperazine affinity, enhanced the diffusion of piperazine across the reaction interface compared with the â-CNF interlayer. This led to an acceleration of the interfacial polymerization process and the formation of a denser membrane structure. Further investigation revealed that the charged interlayers significantly influenced the surface charging properties of the resulting nanofiltration membranes within a 30 nm range of electrostatic effects. Specifically, the â-CNF interlayer conferred a higher negative charge to the membrane surface, while the [Formula: see text]-CNF interlayer endowed the membranes with a lower surface negative charge. Leveraging these differences, the â-i-TFC membranes exhibited exceptional separation performance for divalent anions, achieving a SO42-/Cl- selectivity of 136. Conversely, the [Formula: see text]-i-TFC membrane demonstrated an enhanced separation of divalent cations, displaying a Mg2+/Na+ selectivity of 3.5. This study lays the groundwork for regulating the surface charging properties of polyamide membranes, offering potential advancements in nanofiltration applications.
RESUMO
A nano-immunomodulator (R-NPT NP) comprising a tumor microenvironment (TME) activable resiquimod (R848) and a π-extended NIR-absorbing naphthophenanthrolinetetraone (NPT) has been engineered for spatiotemporal controlled photothermal immunotherapy. R-NPT NP demonstrated excellent photostability, while R848 promoted synergistic immunity as a toll-like receptor 7/8 (TLR7/8) agonist. Upon accumulation at the tumor site, R-NPT NP released R848 in response to redox metabolite glutathione (GSH), triggering dendritic cell (DC) activation. The photothermal effect endowed by R-NPT NP can ablate tumors directly and trigger immunogenic cell death to augment immunity after photoirradiation. The synergistic effect of GSH-liable TLR7/8 agonist and released immunogenic factors leads to a robust evocation of systematic immunity through promoted DC maturation and T cell infiltration. Thus, R-NPT NP with photoirradiation achieved 99.3 % and 98.2 % growth inhibition against primary and distal tumors, respectively.
Assuntos
Imidas , Fatores Imunológicos , Imunoterapia , Naftalenos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Humanos , Naftalenos/química , Naftalenos/farmacologia , Imidas/química , Imidas/farmacologia , Animais , Nanopartículas/química , Camundongos , Microambiente Tumoral/efeitos dos fármacos , Terapia Fototérmica , Imidazóis/química , Imidazóis/farmacologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Linhagem Celular TumoralRESUMO
Adverse childhood experiences (ACEs) are associated with an increased risk of diabetes in adulthood. However, the potential mediational role of sleep duration in this association is unclear. A total of 116, 014 participants in the United States, from the Behavioral Risk Factor Surveillance System (BRFSS) survey in 2020 were involved in the study. The effects of ACE status, different ACEs, and ACE scores on short sleep duration were examined using binary logistic regression analysis, and the association of ACE status, different types of ACEs, and ACE scores with diabetes and the mediating role of short sleep duration were observed. Path analysis was used to investigate short sleep duration as pathways between different types of ACEs and diabetes in adulthood. For the different types of ACEs, alcohol abuse in the household (OR = 1.13, 95%CI 1.08; 1.18), witnessing domestic violence (OR = 1.17, 95%CI 1.11; 1.23), emotional abuse (OR = 1.11, 95%CI 1.06; 1.16), physical abuse (OR = 1.22, 95%CI 1.17; 1.28), sexual abuse (OR = 1.25, 95%CI 1.18; 1.32) and short sleep duration (OR = 1.26, 95%CI 1.21; 1.32) independently increased the odds of diabetes. There was also an indirect relationship between alcohol abuse in the household, witnessing domestic violence, physical abuse, sexual abuse, and diabetes via short sleep duration. Short sleep duration plays a partial mediating role between ACEs and diabetes, including alcohol abuse in the household, witnessing domestic violence, physical and sexual abuse.
Assuntos
Experiências Adversas da Infância , Alcoolismo , Maus-Tratos Infantis , Diabetes Mellitus , Violência Doméstica , Humanos , Estados Unidos/epidemiologia , Criança , Duração do Sono , Diabetes Mellitus/epidemiologia , Maus-Tratos Infantis/psicologiaRESUMO
Due to the high recurrence rate and mortality of venous thrombosis, there is an urgent need for research on antithrombotic strategies. Because of the short half-life, poor targeting capabilities, bleeding complications, and neurotoxic effects of conventional pharmacological thrombolysis methods, it is essential to develop an alternative strategy to noninvasive thrombolysis and decrease the recurrence rate of venous thrombosis. A platelet-mimetic porphyrin-based covalent organic framework-engineered melanin nanoplatform, to target delivery of hirudin to the vein thrombus site for noninvasive thrombolysis and effective anticoagulation, is first proposed. Owing to the thrombus-hosting properties of platelet membranes, the nanoplatform can target the thrombus site and then activate hyperthermia and reactive oxygen species for thrombolysis under near-infrared light irradiation. The photothermal therapy/photodynamic therapy combo can substantially improve the effectiveness (85.7%) of thrombolysis and prevent secondary embolism of larger fragments. Afterward, the highly loaded (97%) and slow-release hirudin (14 days) are effective in preventing the recurrence of blood clots without the danger of thrombocytopenia. The described biomimetic nanostructures offer a promising option for improving the efficacy of thrombolytic therapy and reducing the risk of bleeding complications in thrombus associated diseases.
Assuntos
Trombose , Trombose Venosa , Humanos , Hirudinas/farmacologia , Biomimética , Trombose/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Terapia Trombolítica/métodosRESUMO
The common clinical chemotherapy often brings serious side effects to patients, mainly due to the off-target and leakage of toxic drugs. However, this is fatal for some specific clinical tumors, such as brain tumors and neuroma. This study performs a drug-free approach by encapsulating black phosphorus (BP) and calcium peroxide (CaO2) in liposomes with surface-modified triphenylphosphonium (BCLT) to develop mitochondria targeting calcification for cancer therapy without damaging normal cells. BCLT preferentially accumulates inside tumor mitochondria and then is activated by near-infrared (NIR) laser irradiation to produce abundant PO4 3- and Ca2+ to accelerate in situ mitochondrial mineralization, leading to mitochondrial dysfunction and cancer cell death. More importantly, both PO4 3- and Ca2+ are essential components of metabolism in the body, and random gradient diffusion or premature leakage does not cause damage to adjacent normal cells. This achievement promises to be an alternative to conventional chemotherapy in clinical practice for many specific tumor types.
Assuntos
Mitocôndrias , Fósforo , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Fósforo/química , Lipossomos/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Biomineralização , Linhagem Celular Tumoral , Animais , Peróxidos/química , Peróxidos/metabolismo , Compostos Organofosforados/química , Compostos de Cálcio/química , Raios Infravermelhos , Camundongos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
Hypertension, diabetes, and hyperlipidemia significantly impact chronic diseases and mortality. Magnesium is an essential nutrient for maintaining critical physiological functions, and magnesium deficiency is often associated with adverse health outcomes. In a cross-sectional study of US adults, we aimed to explore dietary magnesium intake and its association with the prevalence of hypertension, diabetes, and hyperlipidemia in US adults over 20 years of age in NHANES 2007-2018. We obtained data on 24,171 samples of hypertension, 9950 samples of diabetes, and 12,149 samples of hyperlipidemia. We used multivariable logistic regression models adjusted for multiple sociodemographic, anthropometric, and lifestyle factors, with participants subdivided into five groups based on quintiles of daily dietary magnesium. After adjusting for the major lifestyle and dietary variables, an independent and significant inverse relationship between dietary magnesium and hypertension, diabetes, and hyperlipidemia was observed. Compared with the lowest quintile of magnesium intake, the prevalence of hypertension, diabetes, and hyperlipidemia was significantly reduced in the highest magnesium quintile. The OR of hypertension in the highest quintile was 0.66 (95% CI: 0.51-0.87; P trend < 0.001), the OR of diabetes was 0.56 (95% CI: 0.39-0.81; P trend < 0.001), and the OR of hyperlipidemia was 0.68 (95% confidence interval: 0.53-0.86; P trend = 0.007). In the subgroup analysis, most of the inverse relationships persisted. Our findings highlight the potential of magnesium-rich foods to prevent hypertension, diabetes, and hyperlipidemia in US adults. This article summarizes and discuss recent findings on: 1) A high dietary magnesium intake was associated with a lower prevalence of hypertension; 2) An inverse relationship between dietary magnesium with diabetes hyperlipidemia; 3) Monitoring and management of magnesium was important.
Assuntos
Diabetes Mellitus , Hiperlipidemias , Hipertensão , Adulto , Humanos , Magnésio , Hiperlipidemias/epidemiologia , Inquéritos Nutricionais , Estudos Transversais , Diabetes Mellitus/epidemiologia , Dieta , Hipertensão/epidemiologia , Fatores de RiscoRESUMO
It is particularly essential to analyze the complex crosslinked networks within polyamide membranes and their correlation with separation efficiency for the insightful tailoring of desalination membranes. However, using the degree of network crosslinking as a descriptor yields abnormal analytical outcomes and limited correlation with desalination performance due to imperfections in segmentation and calculation methods. Herein, we introduce a more rational parameter, denoted as harmonic amide bond density (HABD), to unravel the relationship between the crosslinked networks of polyamide membranes and their desalination performance. HABD quantifies the number of distinct amide bonds per unit mass of polyamide, based on a comprehensive segmentation of polyamide structure and consistent computational protocols derived from X-ray photoelectron spectroscopy data. Compared to its counterpart, HABD overcomes the limitations and offers a more accurate depiction of the crosslinked networks. Empirical data validate that HABD exhibits the expected correlation with the salt rejection and water permeance of reverse osmosis and nanofiltration polyamide membranes. Notably, HABD is applicable for analyzing complex crosslinked polyamide networks formed by highly functional monomers. By offering a powerful toolbox for systematic analysis of crosslinked polyamide networks, HABD facilitates the development of permselective membranes with enhanced performance in desalination applications.
RESUMO
Single-atom catalysts show excellent catalytic performance because of their coordination environments and electronic configurations. However, controllable regulation of single-atom permutations still faces challenges. Herein, we demonstrate that a polarization electric field regulates single atom permutations and forms periodic one-dimensional Au single-atom arrays on ferroelectric Bi4Ti3O12 nanosheets. The Au single-atom arrays greatly lower the Gibbs free energy for CO2 conversion via Au-O=C=O-Au dual-site adsorption compared to that for Au-O=C=O single-site adsorption on Au isolated single atoms. Additionally, the Au single-atom arrays suppress the depolarization of Bi4Ti3O12, so it maintains a stronger driving force for separation and transfer of photogenerated charges. Thus, Bi4Ti3O12 with Au single-atom arrays exhibit an efficient CO production rate of 34.15 µmol·g-1·h-1, â¼18 times higher than that of pristine Bi4Ti3O12. More importantly, the polarization electric field proves to be a general tactic for the syntheses of one-dimensional Pt, Ag, Fe, Co and Ni single-atom arrays on the Bi4Ti3O12 surface.
RESUMO
Mitochondria play critical roles in the regulation of the proliferation and apoptosis of cancerous cells. Targeted induction of mitochondrial dysfunction in cancer cells by multifunctional nanosystems for cancer treatment has attracted increasing attention in the past few years. Numerous therapeutic nanosystems have been designed for precise tumor therapy by inducing mitochondrial dysfunction, including reducing adenosine triphosphate, breaking redox homeostasis, inhibiting glycolysis, regulating proteins, membrane potential depolarization, mtDNA damage, mitophagy dysregulation and so on. Understanding the mechanisms of mitochondrial dysfunction would be helpful for efficient treatment of diseases and accelerating the translation of these therapeutic strategies into the clinic. Then, various strategies to construct mitochondria-targeted nanosystems and induce mitochondrial dysfunction are summarized, and the recent research progress regarding precise tumor therapeutics is highlighted. Finally, the major challenges and an outlook in this rapidly developing field are discussed. This review is expected to inspire further development of novel mitochondrial dysfunction-based strategies for precise treatments of cancer and other human diseases.
Assuntos
Mitocôndrias , Neoplasias , Humanos , Mitocôndrias/metabolismo , Neoplasias/patologia , DNA Mitocondrial/metabolismo , Apoptose , MitofagiaRESUMO
Rapid development of nanotechnology provides promising strategies in biomedicine, especially in tumor therapy. In particular, the cellular uptake of nanosystems is not only a basic premise to realize various biomedical applications, but also a fatal factor for determining the final therapeutic effect. Thus, a systematic and comprehensive summary is necessary to overview the recent research progress on the improvement of nanosystem cellular uptake for cancer treatment. According to the process of nanosystems entering the body, they can be classified into three categories. The first segment is to enhance the accumulation and permeation of nanosystems to tumor cells through extracellular microenvironment stimulation. The second segment is to improve cellular internalization from extracellular to intracellular via active targeting. The third segment is to enhance the intracellular retention of therapeutics by subcellular localization. The major factors in the delivery can be utilized to develop multifunctional nanosystems for strengthening the tumor therapy. Ultimately, the key challenges and prospective in the emerging research frontier are thoroughly outlined. This review is expected to provide inspiring ideas, promising strategies and potential pathways for developing advanced anticancer nanosystems in clinical practice.
Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Transporte Biológico , Humanos , Nanotecnologia , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Microambiente TumoralRESUMO
Most patients are at high risk of thrombosis during cancer treatment. However, the major discrepancy in the therapeutic mechanisms and microenvironment between tumors and thrombosis makes it challenging for a panacea to treat cancer while being able to eliminate the risk of thrombosis. Herein, we developed a biomimetic MnOx/Ag2S nanoflower platform with platelet membrane modification (MnOx@Ag2S@hirudin@platelet membrane: MAHP) for the long-term release of anticoagulant drugs to treat thrombosis together with tumor therapy. This MAHP platform could achieve the targeted delivery of hirudin to the thrombus site and perform the controlled release under the irradiation of near-infrared light, demonstrating effective removal of the thrombus. Moreover, MAHP could inhibit tumor progression and prolong the survival time of mice with thromboembolic complications.
Assuntos
Hirudinas , Trombose , Camundongos , Animais , Hirudinas/farmacologia , Heparina , Trombose/tratamento farmacológico , Trombose/patologia , Plaquetas , Anticoagulantes/farmacologia , Proteínas Recombinantes/farmacologiaRESUMO
Ferroptosis, a newfound non-apoptotic cell death pathway that is iron- and reactive oxygen species (ROS)-dependent, has shown a promise for tumor treatment. However, engineering ferroptosis inducers with sufficient hydrogen peroxide (H2O2) and iron supplying capacity remains a great challenge. To address this issue, herein, we report a powerful nanoreactor by modifying MnO2, glucose oxidase, and polyethylene glycol on iron-based metal-organic framework nanoparticles for disrupting redox and iron metabolism homeostasis, directly providing the Fenton reaction-independent downstream ferroptosis for tumor therapy. By consuming glutathione and oxidizing glucose to increase the H2O2 level in cancer cells and downregulating ferroportin 1 to accumulate intracellular iron ions, the homeostasis disruptor could effectively enhance the ferroptosis. Subsequently, the ferroptosis cells release tumor immune-associated antigens, which combine with in situ injected aptamer-PD-L1 to further strengthen the tumor treatment efficiency. This work not only paves a way to enhance the efï¬cacy of ferroptosis-based cancer therapy by associating intracellular redox homeostasis with the iron metabolism system in tumor cells but also offers an engineered nanoreactor as a promising mimetic antigen for activating immunotherapy.
Assuntos
Ferroptose , Estruturas Metalorgânicas , Linhagem Celular Tumoral , Homeostase , Peróxido de Hidrogênio , Imunoterapia , Ferro , Compostos de Manganês , Nanotecnologia , ÓxidosRESUMO
The second near-infrared (NIR-II)-induced photothermal therapy (PTT) has attracted a great deal of attention in recent years due to its non-invasiveness and because it uses less energy. However, the penetration of photothermal agents into solid tumors is seriously impeded by the dense-tumor extracellular matrix (ECM) containing cross-linked hyaluronic acid (HA), thereby compromising the ultimate therapeutic effects. Herein, acid-labile metal-organic frameworks were employed as nanocarriers to efficiently mineralize hyaluronidase (HAase) and encapsulate Ag2S nanodots by a one-pot approach under mild conditions. The obtained nanocomposites (AHZ NPs) maintained enzyme activity and changed in size to prolong blood circulation and complete delivery of the cargo to the tumor. Moreover, the released HAase could specifically break out the HA to loosen ECM and enable the Ag2S nanodots to breeze through the tumor matrix space and gain access to the deep tumor. Under near-infrared laser irradiation, the AHZ NPs displayed remarkable fluorescence, outstanding photoacoustic signals, and excellent photothermal properties in the whole tumor. This work offers a promising two-pronged strategy via a decrease in nanoparticle size and the degradation of dense ECM for NIR-II multimodal imaging-guided PTT of deep tumors.
Assuntos
Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Ácido Hialurônico/farmacologia , Hialuronoglucosaminidase , Estruturas Metalorgânicas/uso terapêutico , Imagem Multimodal , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Fototerapia , Terapia FototérmicaRESUMO
While checkpoint blockade immunotherapy as a promising clinical modality has revolutionized cancer treatment, it is of benefit to only a subset of patients because of the tumor immunosuppressive microenvironment. Herein, we report that the specified delivery of vitamin C at the tumor site by responsive lipid nanoparticles can efficiently induce oxidative toxicity and the polarization of M1 macrophages, promoting the infiltration of activating cytotoxic T lymphocytes in the tumor microenvironment for intensive immune checkpoint blocking therapy. Both in vitro and in vivo assays demonstrate successful vitamin C-induced polarization of M2 macrophages to M1 macrophages. In vivo transcriptome analysis also reveals the activation mechanism of vitamin C immunity. More importantly, the combination approach displays much better immune response and immune process within the tumor microenvironment than clinical programmed cell death ligand 1 (Anti-PD-L1) alone. This work provides a powerful therapeutic application of vitamin C to amplify Anti-PD-L1 immunotherapy in cancer treatment, which brings hope to patients with clinically insensitive immunity.
Assuntos
Neoplasias , Macrófagos Associados a Tumor , Humanos , Lipossomos/farmacologia , Receptor de Morte Celular Programada 1 , Ácido Ascórbico/farmacologia , Inibidores de Checkpoint Imunológico , Ligantes , Imunoterapia , Microambiente Tumoral , Neoplasias/tratamento farmacológicoRESUMO
The proposal of the aggregation-induced emission (AIE) effect shines a light on the practical application of luminescent materials. The AIE-active luminescence microgels (TPEC MGs) with photo-induced color-changing behavior were developed by integrating positively charged AIE luminogens (AIEgens) into the anionic network of microgels, where AIEgens of TPEC were obtained from the quaternization reaction between tetra-(4-pyridylphenyl)ethylene (TPE-4Py) and 7-(6-bromohexyloxy)-coumarin. The aqueous suspensions of TPEC MGs exhibit a significant AIE effect following the enhancement of quantum yield. In addition, further increase in fluorescence intensity and blueshift occur at elevated temperatures due to the collapse of microgels. The distinctive photochromic behavior of TPEC MGs was observed, which presents as the transition from orange-yellow to blue-green color under UV irradiation, which is different from TPEC in good organic solvents. The phenomenon of color changing can be ascribed to the competition between photodimerization of the coumarin part and photocyclization of TPE-4Py in TPEC. The photochromic TPEC MG aqueous suspensions can be conducted as aqueous microgel inks for information display, encryption, and dynamic anticounterfeiting.
RESUMO
The deepening crisis of freshwater resources has been driving the further development of new types of membrane-based desalination technologies represented by nanofiltration membranes. Solving the existing trade-off limitation on enhancing the water permeance and the rejection of salts is currently one of the most concerned research interests. Here, a facile and scalable approach is proposed to tune the interfacial polymerization by constructing a calcium alginate hydrogel layer on the porous substrates. The evenly coated thin hydrogel layer can not only store amine monomers like the aqueous phase but also suppress the diffusion of amine monomers inside, as well as provide a flat and stable interface to implement the interfacial polymerization. The resultant polyamide nanofilms have a relatively smooth morphology, negatively charged surface, and reduced thickness which facilitate a fast water permeation while maintaining rejection efficiency. As a result, the as-prepared composite membranes show improved water permeance (~30 Lm-2h-1bar-1) and comparable rejection of Na2SO4 (>97%) in practical applications. It is proved to be a feasible approach to manufacturing high-performance nanofiltration membranes with the assist of alginate hydrogel regulating interfacial polymerization.
RESUMO
Graphitic carbon nitride (g-C3N4) has been widely studied as a photocatalyst for the splitting of water to produce hydrogen. In order to solve the problems of limited number of active sites and serious recombination rate of charge-carriers, noble metals are needed as cocatalysts. Here, we selectively anchored Pt nanoparticles (NPs) to specific nitrogen species on the surface of g-C3N4 via heat treatment in argon-hydrogen gas mixture, thus achieving g-C3N4 photocatalyst anchored by highly dispersed homogeneous Pt NPs with the co-existed metallic Pt0 and Pt2+ species. The synergistic effect of highly dispersed metallic Pt0 and Pt2+ species makes the catalyst exhibit excellent photocatalytic performance. Under the full-spectrum solar light irradiation, the photocatalytic hydrogen production rate of the photocatalyst is up to 18.67 mmol·g-1·h-1, which is 5.1 times of the catalyst prepared by non-selective deposition of Pt NPs.
RESUMO
One of the main challenges for tumor vascular infarction in combating cancer lies in failing to produce sustained complete thrombosis. Inspired by the capability of vascular infarction in blocking the delivery of oxygen to aggravate tumor hypoxia, the performance of selective tumor thrombus inducing hypoxia activation therapy to improve the therapeutic index of coagulation-based tumor therapy is presented. By encapsulating coagulation-inducing protease thrombin and a hypoxia-activated prodrug (HAP) tirapazamine into metal-organic framework nanoparticles with a tumor-homing ligand, the obtained nanoplatform selectively activates platelet aggregation at the tumor to induce thrombosis and vascular obstruction therapy by the exposed thrombin. Meanwhile, the thrombus can cut off the blood oxygen supply and potentiate the hypoxia levels to enhance the HAP therapy. This strategy not only addresses the dissatisfaction of vascular therapy, but also conquers the dilemma of inadequate hypoxia in HAP treatment. Since clinical operations such as surgery can be used to induce coagulation, coagulation-based synergistic therapy is promising for translation into a clinical combination regimen.
Assuntos
Pró-Fármacos/química , Trombina/química , Hipóxia Tumoral , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Estruturas Metalorgânicas/química , Camundongos , Camundongos Nus , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Agregação Plaquetária/efeitos dos fármacos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Trombose/patologia , Tirapazamina/química , Transplante Heterólogo , Hipóxia Tumoral/efeitos dos fármacosRESUMO
Chemodynamic therapy (CDT) destroys cancer cells by converting H2O2 or O2 into reactive oxygen species (ROS), but its therapeutic efficacy is restricted by the antioxidant capacity of tumor. Previous solutions focused on strengthening the nanodrugs with the ability to increase ROS production or weaken the antioxidant capacity of cancer cells. Conversely, we here develop a mild nanodrug with negligible side effects. Specifically, the Au@Pt nanozyme decorated on a bacterial surface (Bac-Au@Pt) is reported to achieve precise CDT. Due to the tumor targeting ability of bacteria and catalytic property of Au@Pt nanozyme under acidic conditions, this nanosystem can release ROS to tumor cells effectively. In addition, the interferon gamma released by T cells specifically decreases the intracellular reductants in tumor cells, while having no obvious effect on normal cells. Therefore, a low dose of Bac-Au@Pt achieves a satisfactory therapeutic efficacy to tumor cells and is nontoxic to normal cells even at their acidic components. This nanosystem enables CDT and immunotherapy to mutually benefit and improve by each other, providing a promising strategy to achieve high anticancer efficacy even with a low dose usage.