RESUMO
The free radical generation efficiency of nanozymes in cancer therapy is crucial, but current methods fall short. Alloy nanoparticles (ANs) hold promise for improving catalytic performance due to their inherent electronic effect, but there are limited ways to modulate this effect. Here, a self-driven electric field (E) system utilizing triboelectric nanogenerator (TENG) and AuPd ANs with glucose oxidase (GOx)-like, catalase (CAT)-like, and peroxidase (POD)-like activities is presented to enhance the treatment of 4T1 breast cancer in mice. The E stimulation from TENG enhances the orbital electrons of AuPd ANs, resulting in increased CAT-like, GOx-like, and POD-like activities. Meanwhile, the catalytic cascade reaction of AuPd ANs is further amplified after catalyzing the production of H2 O2 from the GOx-like activities. This leads to 89.5% tumor inhibition after treatment. The self-driven E strategy offers a new way to enhance electronic effects and improve cascade catalytic therapeutic performance of AuPd ANs in cancer therapy.
Assuntos
Nanopartículas , Neoplasias , Neoplasias Orbitárias , Animais , Camundongos , Elétrons , Neoplasias Orbitárias/tratamento farmacológico , Neoplasias/tratamento farmacológico , Glucose Oxidase , Peróxido de HidrogênioRESUMO
Chirality is a prevalent characteristic in nature, where biological systems exhibit a significant preference for specific enantiomers of biomolecules. However, there is a limited exploration into utilizing nanomaterials' chirality to modulate their interactions with intracellular substances. In this study, self-assembled copper-cysteine chiral nanoparticles and explore the influence of their charity on cancer chemodynamic therapy (CDT) are fabricated. Experimental and molecular dynamics (MD) simulation results demonstrate that the copper-l-cysteine chiral nanoparticles (Cu-l-Cys NPs) exhibit a stronger affinity toward l-glutathione (l-GSH) that is overproduced in cancer cells, compared to the copper-d-cysteine enantiomer (Cu-d-Cys NPs). The interaction between Cu-l-Cys NPs and l-GSH triggers a redox reaction that depletes l-GSH and converts Cu2+ into Cu+. Subsequently, Cu+ catalyzes a Fenton-like reaction, decomposing H2O2 into highly cytotoxic hydroxyl radicals (â¢OH) for cancer CDT. In vivo, results confirm that Cu-l-Cys NPs with good biocompatibility elicit a pronounced cancer cell death and effectively inhibit tumor growth. This work proposes a new perspective on chirality-enhanced cancer therapy.
Assuntos
Cobre , Nanopartículas , Neoplasias , Cobre/química , Humanos , Nanopartículas/química , Animais , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Aminoácidos/química , Glutationa/química , Glutationa/metabolismo , Linhagem Celular Tumoral , Cisteína/química , Simulação de Dinâmica Molecular , Camundongos , EstereoisomerismoRESUMO
The patient-centered healthcare requires timely disease diagnosis and prognostic assessment, calling for individualized physiological monitoring. To assess the postoperative hemodynamic status of patients, implantable blood flow monitoring devices are highly expected to deliver real time, long-term, sensitive, and reliable hemodynamic signals, which can accurately reflect multiple physiological conditions. Herein, an implantable and unconstrained vascular electronic system based on a piezoelectric sensor immobilized is presented by a "growable" sheath around continuously growing arterial vessels for real-timely and wirelessly monitoring of hemodynamics. The piezoelectric sensor made of circumferentially aligned polyvinylidene fluoride nanofibers around pulsating artery can sensitively perceive mechanical signals, and the growable sheath bioinspired by the structure and function of leaf sheath has elasticity and conformal shape adaptive to the dynamically growing arterial vessels to avoid growth constriction. With this integrated and smart design, long-term, wireless, and sensitive monitoring of hemodynamics are achieved and demonstrated in rats and rabbits. It provides a simple and versatile strategy for designing implantable sensors in a less invasive way.
Assuntos
Eletrônica , Hemodinâmica , Humanos , Animais , Coelhos , Ratos , Próteses e Implantes , Monitorização FisiológicaRESUMO
Sonodynamic therapy (SDT) is regarded as a new-rising strategy for cancer treatment with low invasiveness and high tissue penetration, but the scarcity of high-efficiency sonosensitizers has seriously hindered its application. Herein, the iron-doped and oxygen-deficient bismuth tungstate nanosheets (BWO-Fe NSs) with piezotronic effect are synthesized for enhanced SDT. Due to the existence of oxygen defects introduced through Fe doping, the bandgap of BWO-Fe is significantly narrowed so that BWO-Fe can be more easily activated by exogenous ultrasound (US). The oxygen defects acting as the electron traps inhibit the recombination of US-induced electrons and holes. More importantly, the dynamically renewed piezoelectric potential facilitates the migration of electrons and holes to opposite side and causes energy band bending, which further promotes the production of reactive oxygen species. Furthermore, Fe doping endows BWO-Fe with Fenton reactivity, which converts hydrogen peroxide (H2 O2 ) in tumor microenvironment into hydroxyl radicals (â¢OH), thereby amplifying the cellular oxidative damage and enhancing SDT. Both in vitro and in vivo experiments illustrate their high cytotoxicity and tumor suppression rate against refractory breast cancer in mice. This work may provide an alternative strategy to develop oxygen-deficient piezoelectric sonosensitizers for enhanced SDT via doping metal ions.
Assuntos
Neoplasias , Terapia por Ultrassom , Camundongos , Animais , Oxigênio , Bismuto , Ferro , Espécies Reativas de Oxigênio , Neoplasias/terapia , Neoplasias/patologia , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
The efficacy of sonodynamic therapy (SDT) mainly relies on the sonosensitizers, which generate reactive oxygen species (ROS) upon ultrasound (US) stimulation. However, the limited availability of high-efficiency sonosensitizers hampers the therapeutic effectiveness of SDT as a standalone modality. In this work, a robust sonodynamic and gas cancer therapeutic platform is constructed based on strontium (Sr) doped barium titanate (BST) piezoelectric nanoparticles functionalized with L-arginine (BST@LA). The doping of Sr into A site of the ABO3 piezoelectric nanocrystals not only introduces oxygen vacancies into the nanoparticles and enhance the intrinsic piezoelectricity, but also narrows the semiconductor band gap and enhances charge carrier migration, all of which facilitate the sonodynamic production of superoxide anion (â¢O2 - ) and hydroxyl radical (â¢OH). In addition, the generated ROS promotes the decomposition of the surface-tethered LA, enabling the controlled release of nitric oxide (NO) gas at the tumor site, thereby achieving a combination therapeutic effect. In vivo experiments exhibit remarkable tumor suppression rate (89.5%) in 4T1 tumor mice model, demonstrating the effectiveness of this strategy. The ion doping and oxygen vacancy engineering to improve sonosensitizers, along with the synergistic combination of sonodynamic and gas therapy, provides promising avenues for improving cancer therapy.
Assuntos
Neoplasias , Estrôncio , Animais , Camundongos , Óxido Nítrico , Espécies Reativas de Oxigênio , Ácido Linoleico , Oxigênio , Neoplasias/terapiaRESUMO
Sonodynamic therapy (SDT) as an emerging method for cancer therapy has encountered difficulty in insufficient production of reactive oxygen species (ROS), especially in tumor microenvironment (TME) with elevated antioxidants and hypoxic conditions. In this work, the authors have fabricated heterostructured manganese dioxide (MnO2)-coated BaTiO3 nanoparticles (BTO@M NPs) as a piezoelectric sonosensitizer, which exhibits the capacity of remodeling TME and multienzyme-like catalysis for boosting SDT. Benefitting from the piezotronic effect, the formation of a p-n junction between MnO2 and piezoelectric BTO with a built-in electric field and band bending efficiently promotes the separation of charge carriers, facilitating the generation of superoxide anion (â¢O2 -) and hydroxyl radical (â¢OH) under ultrasound (US) stimulation. Moreover, BTO@M NPs can catalyze the overexpressed hydrogen peroxide (H2O2) in TME to produce oxygen for replenishing the gas source in SDT, and also deplete antioxidant glutathione (GSH), realizing TME remodeling. During this process, the reduced Mn(II) can convert H2O2 into â¢OH, further amplifying cellular oxidative damage. With these combination effects, the versatile BTO@M NPs exhibit prominent cytotoxicity and tumor growth inhibition against 4T1 breast cancer. This work provides a feasible strategy for constructing high-efficiency sonosensitizers for cancer SDT.
RESUMO
Electric-field-based stimulation is emerging as a new cancer therapeutic modality through interfering with cell mitosis. To address its limitations of complicated wire connections, bulky devices, and coarse spatial resolution, an improved and alternative method is proposed for wirelessly delivering electrical stimulation into tumor tissues through designing an implantable, biodegradable, and wirelessly controlled therapeutic triboelectric nanogenerator (ET-TENG). With the excitation of ultrasound (US) to the ET-TENG, the implanted ET-TENG can generate an alternating current voltage and concurrently release the loaded anti-mitotic drugs into tumor tissues, which synergistically disrupts the assembly of microtubules and filament actins, induces cell cycle arrest, and finally enhances cell death. With the assistance of US, the device can be completely degraded after the therapy, getting free of a secondary surgical extraction. The device can not only work around those unresectable tumors, but also provides a new application of wireless electric field in cancer therapy.
Assuntos
Actinas , Neoplasias , Humanos , Morte Celular , Estimulação Elétrica , Microtúbulos , Neoplasias/tratamento farmacológicoRESUMO
Ultrasound (US)-triggered sonodynamic therapy (SDT) is an emerging method for treating cancer due to its non-invasive nature and high-depth tissue penetration ability. However, current sonosensitizers commonly have unsatisfactory quantum yields of free radicals. In this work, we have developed unique organic semiconductor π-conjugated covalent organic framework nanocages (COFNs) as highly efficient sonosensitizers to boost free radical (1O2 and â¢OH) production and cancer therapy. With the hollow and porous structure and band transport behavior, COFNs displayed remarkably improved SDT performance through enhanced electron utilization and cavitation effect, with a 1.8-fold increase in US pressure and a 64.8% increase in 1O2 production relative to the core-shell-structured COF under US irradiation. The in vitro and in vivo experimental results verified the elevated SDT performance, showing a high tumor suppression of 91.4% against refractory breast cancer in mice. This work provides a promising strategy to develop high-performance sonosensitizers for cancer therapy.
Assuntos
Estruturas Metalorgânicas , Neoplasias , Terapia por Ultrassom , Camundongos , Animais , Estruturas Metalorgânicas/farmacologia , Terapia por Ultrassom/métodos , Neoplasias/terapia , Neoplasias/patologia , Ultrassonografia , Radicais Livres , Linhagem Celular Tumoral , Espécies Reativas de OxigênioRESUMO
The efficacy of cancer catalytic therapy is still hindered by the inefficient generation of reactive oxygen species (ROS). Herein, we report a self-driven electrical stimulation-promoted cancer catalytic therapy and chemotherapy by integrating a human-driven triboelectric nanogenerator (TENG) with an implantable and biodegradable nanofibrous patch. The gelatin/polycaprolactone nanofibrous patch incorporates doxorubicin (DOX) and graphitic carbon nitride (g-C3N4), in which the peroxidase (POD)-like activity of g-C3N4 to produce hydroxyl radical (â¢OH) can be distinctly enhanced by the self-driven electrical stimulation for 4.12-fold, and simultaneously DOX can be released to synergize the therapy, especially under a weakly acidic tumor microenvironment (TME) condition. The in vitro and in vivo experimental results on a mouse breast cancer model demonstrate superior tumor suppression outcome. The self-powered electrical stimulation-enhanced catalytic therapy and chemotherapy via multifunctional nanofibrous patches proposes a new complementary strategy for the catalytic therapy of solid tumors.
Assuntos
Nanofibras , Neoplasias , Camundongos , Animais , Humanos , Próteses e Implantes , Eletricidade , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Estimulação Elétrica , Microambiente TumoralRESUMO
Sonodynamic therapy (SDT) is considered as a new-rising strategy for cancer therapeutics, but the inefficient production of reactive oxygen species (ROS) by current sonosensitizers seriously hinders its further applications. Herein, a piezoelectric nanoplatform is fabricated for enhancing SDT against cancer, in which manganese oxide (MnOx) with multiple enzyme-like activities is loaded on the surface of piezoelectric bismuth oxychloride nanosheets (BiOCl NSs) to form a heterojunction. When exposed to ultrasound (US) irradiation, piezotronic effect can remarkably promote the separation and transport of US-induced free charges, and further enhance ROS generation in SDT. Meanwhile, the nanoplatform shows multiple enzyme-like activities from MnOx, which can not only downregulate the intracellular glutathione (GSH) level, but also disintegrate endogenous hydrogen peroxide (H2O2) to generate oxygen (O2) and hydroxyl radicals (â¢OH). As a result, the anticancer nanoplatform substantially boosts ROS generation and reverses tumor hypoxia. Ultimately, it reveals remarkable biocompatibility and tumor suppression in a murine model of 4 T1 breast cancer under US irradiation. This work provides a feasible pathway for improving SDT using piezoelectric platforms.
Assuntos
Peróxido de Hidrogênio , Neoplasias , Camundongos , Humanos , Animais , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/terapia , Oxigênio/metabolismo , Linhagem Celular TumoralRESUMO
Recently, with the rational design of transition metal-containing nanoagents, chemodynamic therapy (CDT) has been developed and considered a promising method for cancer therapy through Fenton and Fenton-like reaction-induced hydroxyl radical (·OH) generation and cellular oxidative damage. However, it is still a great challenge to realize high reactive oxygen species (ROS) generation and therapeutic efficiency under the strict conditions of the tumor microenvironment (TME). Herein, we design and fabricate a TME-responsive core-shell nanocage composed of a CaCO3 nanolayer and a heterogeneous CoP core (CaCO3@CoP, CCP) with the synergy of CDT and calcium overload to maximize oxidative damage and enhance cancer therapy. The CaCO3 nanoshell is sensitive to pH and can be rapidly degraded upon endocytosis, leading to intracellular Ca2+ accumulation, which further triggers the production of mitochondrial ROS. Subsequently, the CoP hollow nanocage with fully exposed Co active sites has high Fenton-like reactive activity to produce ·OH and induce mitochondrial damage. Mitochondrial damage and ROS elevation, in turn, can modulate Ca2+ dynamics and augment calcium overload. The reciprocal interaction and loop feedback between calcium overload and photoenhanced ROS generation via photothermal therapy (PTT) can further trigger the immunogenic cell death (ICD) process to activate the maturation of dendritic cells (DCs), activation of cytotoxic and helper T cells, and excretion of proinflammatory cytokines to enhance antitumor immunity in vivo. With the butterfly effect, CCP finally brings forth a greatly enhanced cancer therapeutic outcome in murine models.
Assuntos
Neoplasias , Fotoquimioterapia , Animais , Cálcio/metabolismo , Linhagem Celular Tumoral , Camundongos , Neoplasias/tratamento farmacológico , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Gas therapy is an emerging technology for improving cancer therapy with high efficiency and low side effects. However, due to the existence of the gatekeeper of the blood-brain barrier (BBB) and the limited availability of current drug delivery systems, there still have been no reports on gas therapy for intracranial neuroglioma. Herein, an integrated, self-powered, and wirelessly controlled gas-therapy system is reported, which is composed of a self-powered triboelectric nanogenerator (TENG) and an implantable nitric oxide (NO) releasing device for intracranial neuroglioma therapy. In the system, the patient self-driven TENG converts the mechanical energy of body movements into electricity as a sustainable and self-controlled power source. When delivering energy to light a light-emitting diode in the implantable NO releasing device via wireless control, the encapsulated NO donor s-nitrosoglutathione (GSNO) can generate NO gas to locally kill the glioma cells. The efficacy of the proof-of-concept system in subcutaneous 4T1 breast cancer model in mice and intracranial glioblastoma multiforme in rats is verified. This self-powered gas-therapy system has great potential to be an effective adjuvant treatment modality to inhibit tumor growth, relapse, and invasion via teletherapy.
Assuntos
Nanotecnologia , Óxido Nítrico , Ratos , Camundongos , Animais , Recidiva Local de Neoplasia , Fontes de Energia Elétrica , EletricidadeRESUMO
Reactive oxygen species (ROS) production efficiencies of the nanocatalysts are highly desired for cancer therapy, but currently the ROS generation efficiency is still far from defecting the tumors. Therefore, improving their ROS generation ability is highly desirable for cancer therapy. Herein, inspired by the electrostatic preorganization effect during the catalysis of natural protein enzymes, a human self-driven catalysis-promoting system, TENG-CatSystem is developed, to improve catalytic cancer therapy. The TENG-CatSystem is mainly composed of three elements: a human self-driven triboelectric nanogenerator (TENG) as the electric field stimulator to provide electric pulses with high biosafety, a nanozyme comprising a 1D ferriporphyrin covalent organic framework coated on a carbon nanotube (COF-CNT) to generate ROS, and a COF-CNT-embedded conductive hydrogel that can be injected into the tumor tissues to increase local accumulation of COF-CNT and decrease the electrical impedances of tissues. Under the human self-generated electric field provided by the wearable TENG, the peroxidase-like activity of the COF-CNT is fourfold higher than that without an electric field. Highly malignant 4T1 breast carcinoma in mice is significantly suppressed using the TENG-CatSystem. The human self-driven TENG-CatSystem not only demonstrates high catalytic ROS generation efficiency for improved cancer therapy, but also offers a new therapeutic mode for self-driven at-home therapy.
Assuntos
Nanotubos de Carbono , Neoplasias , Animais , Catálise , Elétrons , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Espécies Reativas de OxigênioRESUMO
Covalent organic frameworks (COFs) as a type of porous and crystalline covalent organic polymer are built up from covalently linked and periodically arranged organic molecules. Their precise assembly, well-defined coordination network, and tunable porosity endow COFs with diverse characteristics such as low density, high crystallinity, porous structure, and large specific-surface area, as well as versatile functions and active sites that can be tuned at molecular and atomic level. These unique properties make them excellent candidate materials for biomedical applications, such as drug delivery, diagnostic imaging, and disease therapy. To realize these functions, the components, dimensions, and guest molecule loading into COFs have a great influence on their performance in various applications. In this review, we first introduce the influence of dimensions, building blocks, and synthetic conditions on the chemical stability, pore structure, and chemical interaction with guest molecules of COFs. Next, the applications of COFs in cancer diagnosis and therapy are summarized. Finally, some challenges for COFs in cancer therapy are noted and the problems to be solved in the future are proposed.
RESUMO
The production of reactive oxygen species (ROS) to elicit lethal cellular oxidative damage is an attractive pathway to kill cancer cells, but it is still hindered by the low ROS production efficiency of the current methods. Herein, we design a one-dimensional (1D) π-π conjugated ferriporphyrin covalent organic framework on carbon nanotubes (COF-CNT) for activating nanocatalytic and photodynamic cancer therapy. The COF-CNT can catalyze the generation of ROS and O2 in the tumor microenvironment (TME), and realize a self-oxygen-supplying PDT under near-infrared (NIR) light irradiation, simultaneously. With the full electron delocalization at the atomically dispersed active center, the catalytic activity of COF-CNT with extended π-conjugation is 6.8 times higher than that without the π-conjugated structure. The formation of the COF structure with π-π conjugation also changes the density of states (DOS) profile of its functional building block for improving PDT. Through one single treatment, it successfully achieves complete tumor regression of 4T1 breast carcinoma in mice with immunoregulation.
Assuntos
Estruturas Metalorgânicas , Nanopartículas , Nanotubos de Carbono , Neoplasias , Fotoquimioterapia , Animais , Estruturas Metalorgânicas/química , Camundongos , Nanopartículas/química , Neoplasias/terapia , Fotoquimioterapia/métodos , Microambiente TumoralRESUMO
In the present study, the nanotubes of 5-(4-hydroxyphenyl)-10, 15, 20-tri(4-chlorophenyl) porphyrin (p-HTClPP) (1) and 5-(4-hydroxyphenyl)-10, 15, 20-tri(4-chlorophenyl) porphyrin cobalt (p-HTClPPCo) (2) were successfully prepared by using anodize alumina oxide (AAO) template method. The p-HTClPP and p-HTClPPCo nanotubes have been confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), electronic absorption spectra, fluorescence spectroscopy, fourier transform infrared spectroscopy (FT-IR), low-angle X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS) techniques. Both p-HTClPPCo and p-HTClPP nanotubes showed excellent sensitivity, reproducibility and selectivity toward NO2. Especially the prepared sensor of p-HTClPPCo nanotubes exhibited faster response/recovery characteristics and lower detection limit of NO2 (up to 500ppb) than that of p-HTClPP nanotubes, which pave a new avenue in the gas sensitive field.
RESUMO
A sandwich-type (phthalocyaninato)(porphyrinato) europium double-decker complex Eu(TPyP){Pc-(OC8H17)8} [TPyP = meso-tetra(4-pyridyl)porphyrin; Pc-(OC8H17)8 = 2,3,9,10,16,17,23,24-octakis(octyloxy)phthalocyanine] (2) was designed and prepared. For comparative studies, Eu(TPyP)(Pc) (1) was also prepared. Highly ordered nanotubes of complexes 1 and 2 were successfully fabricated by using an anodized alumina oxide (AAO) template method. The nanotubes were comparatively investigated by electronic absorption spectra, scanning electron microscopy (SEM), low-angle X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and energy dispersive spectroscopy (EDS) techniques. Both nanotubes of complexes 1 and 2 showed good conductivities and presented an efficient gas sensing platform for the ultrasensitive detection of NO2 at room temperature. In particular, the detection limit and response/recovery times for the proposed sensors based on complex 2 were lower and faster than those of complex 1, indicating the significant effect of a molecular packing mode on tuning the gas sensing performance of organic semiconductors.