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1.
Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS‐scavenging, and osteoinductive porous Ti scaffold is prepared by the on‐surface in situ assembly of a polypyrrole‐polydopamine‐hydroxyapatite (PPy‐PDA‐HA) film through a layer‐by‐layer pulse electrodeposition (LBL‐PED) method. During LBL‐PED, the PPy‐PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy‐PDA‐HA films. Ultimately, the PPy‐PDA‐HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy‐PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.  相似文献   

2.
Silicon dioxide (SiO2), titanium dioxide (TiO2), and zinc oxide (ZnO) are currently among the most widely used nanoparticles (NPs) in the food industry. This could potentially lead to unintended exposure of the gastrointestinal tract to these NPs. This study aims to investigate the potential side‐effects of these food‐borne NPs on intestinal cells and to mechanistically understand the observed biological responses. Among the panel of tested NPs, ZnO NPs are the most toxic. Consistently in all three tested intestinal cell models, ZnO NPs invoke the most inflammatory responses from the cells and induce the highest intracellular production of reactive oxygen species (ROS). The elevated ROS levels induce significant damage to the DNA of the cells, resulting in cell‐cycle arrest and subsequently cell death. In contrast, both SiO2 and TiO2 NPs elicit minimum biological responses from the intestinal cells. Overall, the study showcases the varying capability of the food‐borne NPs to induce a cellular response in the intestinal cells. In addition to physicochemical differences in the NPs, the genetic landscape of the intestinal cell models governs the toxicology profile of these food‐borne NPs.  相似文献   

3.
It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low‐bandgap donor–acceptor (D–A)‐type conjugated‐polymer nanoparticles (CP‐NPs) are developed to afford a highly efficient singlet‐to‐triplet transition and photothermal conversion for near‐infrared (NIR) light‐induced photodynamic (PDT)/photothermal (PTT) treatment. CP‐NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP‐NPs undergo singlet‐to‐triplet intersystem crossing through charge transfer in the excited D–A system and simultaneous nonradiative decay from the electron‐deficient electron acceptor isoindigo derivative under single‐wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP‐NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light‐triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP‐NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof‐of‐concept design of D–A‐type conjugated‐polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive cancer therapy.  相似文献   

4.
Radiotherapy (RT) has been extensively utilized for clinical cancer therapy, however, excessive generation of reactive oxygen species (ROS) is becoming a main cause for radiation‐induced heart disease (RIHD). Ganoderma lucidum spore oil (GLSO) is a popular functional food composite with potent antioxidant activity, but it is compromised by poor solubility and stability for further application. Therefore, a strategy for rational fabrication of GLSO@P188/PEG400 nanosystem (NS) is demonstrated in this study to realize good water solubility and achieve enhanced protection against RIHD. As expected, GLSO@P188/PEG400 NS can attenuate X‐ray‐induced excessive ROS levels thanks to its enhanced free radical scavenging capability, simultaneously protecting on mitochondria from X‐ray irradiation (IR). Moreover, GLSO@P188/PEG400 NS alleviates DNA damage and promotes self‐repair processes against IR, thus recovering G0/G1 proportion back to normal levels. Furthermore, pre‐ and post‐treated GLSO@P188/PEG400 NS demonstrates potential protection on heart from X‐rays in vivo, as evidenced by attenuating cardiac dysfunction and myocardial fibrosis. Meanwhile, the cell antioxidant capacity (including T‐SOD, MDA, and GSH‐x) stays in balance during this process. This study not only provides a promising strategy for facile nanolization of functional food composites with hydrophobic defects but also sheds light on their cardiac protection and action mechanisms against IR‐induced disease.  相似文献   

5.
Nanoparticle (NP) exposure may induce oxidative stress through generation of reactive oxygen and nitrogen species, which can lead to cellular and tissue damage. The digestive system is one of the initial organs affected by NP exposure. Here, it is demonstrated that exposure to metal oxide NPs induces differential changes in zebrafish intestinal NO concentrations. Intestinal NO concentrations are quantified electrochemically with a carbon fiber microelectrode inserted in the intestine of live embryos. Specificity of the electrochemical signals is demonstrated by NO‐specific pharmacological manipulations and the results are correlated with the 4,5‐diaminofluorescein‐diacetate (DAF‐FM‐DA). NPs are demonstrated to either induce or reduce physiological NO levels depending on their redox reactivity, type and dose. NO level is altered following exposure of zebrafish embryos to CuO and CeO2 NPs at various stages and concentrations. CuO NPs increase NO concentration, suggesting an intestinal oxidative damage. In contrast, low CeO2 NP concentration exposure significantly reduces NO levels, suggesting NO scavenging activity. However, high concentration exposure results in increased NO. Alterations in NO concentration suggest changes in intestinal physiology and oxidative stress, which will ultimately correspond to NPs toxicity. This work also demonstrates the use of electrochemistry to monitor in vivo changes of NO within zebrafish organs.  相似文献   

6.
Developing efficient and low‐cost defective carbon‐based catalysts for the oxygen reduction reaction (ORR) is essential to metal–air batteries and fuel cells. Active sites engineering toward these catalysts is highly desirable but challenging to realize boosted catalytic performance. Herein, a sandwich‐like confinement route to achieve the controllable regulation of active sites for carbon‐based catalysts is reported. In particular, three distinct catalysts including metal‐free N‐doped carbon (NC), single Co atoms dispersed NC (Co–N–C), and Co nanoparticles‐contained Co–N–C (Co/Co–N–C) are controllably realized and clearly identified by synchrotron radiation‐based X‐ray spectroscopy. Electrochemical measurements suggest that the Co/Co–N–C catalyst delivers optimized ORR performance due to the rich Co–Nx active sites and their synergistic effect with metallic Co nanoparticles. This work provides deep insight for rationally designing efficient ORR catalyst based on active sites engineering.  相似文献   

7.
Photodynamic therapy (PDT), as an emerging clinically approved modality, has been used for treatment of various cancer diseases. Conventional PDT strategies are mainly focused on superficial lesions because the wavelength of illumination light of most clinically approved photosensitizers (PSs) is located in the UV/VIS range that possesses limited tissue penetration ability, leading to ineffective therapeutic response for deep‐seated tumors. The combination of PDT and nanotechnology is becoming a promising approach to fight against deep tumors. Here, the rapid development of new PDT modalities based on various smartly designed nanocomposites integrating with conventionally used PSs for deep tumor treatments is introduced. Until now many types of multifunctional nanoparticles have been studied, and according to the source of excitation energy they can be classified into three major groups: near infrared (NIR) light excited nanomaterials, X‐ray excited scintillating/afterglow nanoparticles, and internal light emission excited nanocarriers. The in vitro and in vivo applications of these newly developed PDT modalities are further summarized here, which highlights their potential use as promising nano‐agents for deep tumor therapy.  相似文献   

8.
In this work, a ZnO based nanococktail with programmed functions is designed and synthesized for self‐synergistic tumor targeting therapy. The nanococktail can actively target tumors via specific interaction of hyaluronic acid (HA) with CD44 receptors and respond to HAase‐rich tumor microenvironment to induce intracellular cascade reaction for controlled therapy. The exposed cell‐penetrating peptide (R8) potentiates the cellular uptake of therapeutic nanoparticles into targeted tumor cells. Then ZnO cocktail will readily degrade in acidic endo/lysosomes and induce the production of desired reactive oxygen species (ROS) in situ. The destructive ROS not only leads to serious cell damage but also triggers the on‐demand drug release for precise chemotherapy, thus achieving enhanced antitumor efficiency synergistically. After tail vein injection of ZnO cocktail, a favorable tumor apoptosis rate (71.2 ± 8.2%) is detected, which is significantly superior to that of free drug, doxorubicin (12.9 ± 5.2%). Both in vitro and in vivo studies demonstrate that the tailor‐made ZnO cocktail with favorable biocompatibility, promising tumor specificity, and self‐synergistically therapeutic capacity opens new avenues for cancer therapy.  相似文献   

9.
Catalytic nanomaterials can be used extrinsically to combat diseases associated with a surplus of reactive oxygen species (ROS). Rational design of surface morphologies and appropriate doping can substantially improve the catalytic performances. In this work, a class of hollow polyvinyl pyrrolidone‐protected PtPdRh nanocubes with enhanced catalytic activities for in vivo free radical scavenging is proposed. Compared with Pt and PtPd counterparts, ternary PtPdRh nanocubes show remarkable catalytic properties of decomposing H2O2 via enhanced oxygen reduction reactions. Density functional theory calculation indicates that the bond of superoxide anions breaks for the energetically favorable status of oxygen atoms on the surface of PtPdRh. Viability of cells and survival rate of animal models under exposure of high‐energy γ radiation are considerably enhanced by 94% and 50% respectively after treatment of PtPdRh nanocubes. The mechanistic investigations on superoxide dismutase (SOD) activity, malondialdehyde amount, and DNA damage repair demonstrate that hollow PtPdRh nanocubes act as catalase, peroxidase, and SOD analogs to efficiently scavenge ROS.  相似文献   

10.
Hypoxia, a common feature within many types of solid tumors, is known to be closely associated with limited efficacy for cancer therapies, including radiotherapy (RT) in which oxygen is essential to promote radiation‐induced cell damage. Here, an artificial nanoscale red‐blood‐cell system is designed by encapsulating perfluorocarbon (PFC), a commonly used artificial blood substitute, within biocompatible poly(d ,l ‐lactide‐co‐glycolide) (PLGA), obtaining PFC@PLGA nanoparticles, which are further coated with a red‐blood‐cell membrane (RBCM). The developed PFC@PLGA‐RBCM nanoparticles with the PFC core show rather efficient loading of oxygen, as well as greatly prolonged blood circulation time owing to the coating of RBCM. With significantly improved extravascular diffusion within the tumor mass, owing to their much smaller nanoscale sizes compared to native RBCs with micrometer sizes, PFC@PLGA‐RBCM nanoparticles are able to effectively deliver oxygen into tumors after intravenous injection, leading to greatly relieved tumor hypoxia and thus remarkably enhanced treatment efficacy during RT. This work thus presents a unique type of nanoscale RBC mimic for efficient oxygen delivery into solid tumors, favorable for cancer treatment by RT, and potentially other types of therapy as well.  相似文献   

11.
With the prominent progress of biomedical engineering, materials with high biocompatibility and versatile functions are urgently needed. So far, hierarchical structures in nature have shed some light on the design of high performance materials both in concept and implementation. Inspired by these, the hierarchical micro‐/nanostructures of human hair are explored and human hair is further broken into hierarchical microparticles (HMP) and hierarchical nanoparticles (HNP) with top‐down procedures. Compared with commercialized carriers, such as liposomes or albumin nanoparticles, the obtained particles exhibit high hemocompatibility and negligible immunogenicity. Furthermore, these materials also display attentional abilities in the aspects of light absorption and free radical scavenging. It is found that HMP and HNP can prevent skin from UV‐induced damage and relieve symptoms of cataract in vitro. Besides, both HMP and HNP show satisfactory photothermal conversion ability. By using microcomputed tomography and intravital fluorescence microscopy, it is found that warfarin‐loaded HMP can rescue mice from vein thrombosis. In another aspect, HNP modified with tumor targeted aptamers exhibit dramatic antineoplastic effect, and suppress 96.8% of tumor growth in vivo. Thus, the multifaceted materials described here might provide a new tool for addressing biomedical challenges.  相似文献   

12.
Combining chemotherapy and radiotherapy (chemoradiotherapy) has been widely applied in many clinical practices, showing promises in enhancing therapeutic outcomes. Nontoxic nanocarriers that not only are able to deliver chemotherapeutics into tumors, but could also act as radiosensitizers to enhance radiotherapy would thus be of great interest in the development of chemoradiotherapies. To achieve this aim, herein mesoporous tantalum oxide (mTa2O5) nanoparticles with polyethylene glycol (PEG) modification are fabricated. Those mTa2O5‐PEG nanoparticles could serve as a drug delivery vehicle to allow efficient loading of chemotherapeutics such as doxorubicin (DOX), whose release appears to be pH responsive. Meanwhile, owing to the interaction of Ta with X‐ray, mTa2O5‐PEG nanoparticles could offer an intrinsic radiosensitization effect to increase X‐ray‐induced DNA damages during radiotherapy. As a result, DOX‐loaded mTa2O5‐PEG (mTa2O5‐PEG/DOX) nanoparticles can offer a strong synergistic therapeutic effect during the combined chemoradiotherapy. Furthermore, in chemoradiotherapy, such mTa2O5‐PEG/DOX shows remarkably reduced side effects compared to free DOX, which at the same dose appears to be lethal to animals. This work thus presents a new type of mesoporous nanocarrier particularly useful for the delivery of safe and effective chemoradiotherapy.  相似文献   

13.
Nanoparticles hold a great promise in biomedical science. However, due to their unique physical and chemical properties they can lead to overproduction of intracellular reactive oxygen species (ROS). As an important mechanism of nanotoxicity, there is a great need for sensitive and high‐throughput adaptable single‐cell ROS detection methods. Here, fluorescence lifetime imaging microscopy (FLIM) is employed for single‐cell ROS detection (FLIM‐ROX) providing increased sensitivity and enabling high‐throughput analysis in fixed and live cells. FLIM‐ROX owes its sensitivity to the discrimination of autofluorescence from the unique fluorescence lifetime of the ROS reporter dye. The effect of subcytotoxic amounts of cationic gold nanoparticles in J774A.1 cells and primary human macrophages on ROS generation is investigated. FLIM‐ROX measures very low ROS levels upon gold nanoparticle exposure, which is undetectable by the conventional method. It is demonstrated that cellular morphology changes, elevated senescence, and DNA damage link the resulting low‐level oxidative stress to cellular adverse effects and thus nanotoxicity. Multiphoton FLIM‐ROX enables the quantification of spatial ROS distribution in vivo, which is shown for skin tissue as a target for nanoparticle exposure. Thus, this innovative method allows identifying of low‐level ROS in vitro and in vivo and, subsequently, promotes understanding of ROS‐associated nanotoxicity.  相似文献   

14.
Persistent luminescence nanoparticles (PLNPs) with rechargeable near‐infrared afterglow properties attract much attention for tumor diagnosis in living animals since they can avoid tissue autofluorescence and greatly improve the signal‐to‐background ratio. Using UV, visible light, or X‐ray as excitation sources to power up persistent luminescence (PL) faces the challenges such as limited tissue penetration, inefficient charging capability, or tissue damage caused by irradiation. Here, it is proved that radiopharmaceuticals can efficiently excite ZnGa2O4:Cr3+ nanoparticles (ZGCs) for both fluorescence and afterglow luminescence via Cerenkov resonance energy transfer as well as ionizing radiation. 18F‐FDG, a clinically approved tumor‐imaging radiopharmaceutical with a short decay half‐life around 110 min, is successfully used as the internal light source to in vivo excite intravenously injected ZGCs for tumor luminescence imaging over 3 h. The luminescence with similar decay time can be re‐obtained for multiple times upon injection of 18F‐FDG at any time needed with no health concern. It is believed this strategy can not only provide tumor luminescence imaging with high sensitivity, high contrast, and long decay time at desired time, but also guarantee the patients much less radiation exposure, greatly benefiting image‐guided surgery in the future.  相似文献   

15.
A key characteristic of radiation-induced oral mucositis (RIOM) is oxidative stress mediated by the “reactive oxygen species (ROS) storm” generated from water radiolysis, resulting in severe pathological lesions, accompanied by a disturbance of oral microbiota. Therefore, a sprayable in situ hydrogel loaded with “free radical sponge” fullerenols (FOH) is developed as antioxidant agent for RIOM radioprotection. Inspired by marine organisms, 3,4,5-trihydroxyphenylalanine (TOPA) which is enriched in ascidians is grafted to clinically approved temperature-switchable Pluronic F127 to produce gallic acid (containing the TOPA fragment)-modified Pluronic F127 (MGA) hydrogels to resist the fast loss of FOH via biomimetic adhesion during oral movement and saliva erosion. Based on this, progressive RIOM found in mice is alleviated by treatment of FOH-loaded MGA hydrogels whether pre-irradiation prophylactic administration or post-irradiation therapeutic administration, which contributes to maintaining the homeostasis of oral microbiota. Mechanistically, FOH inhibits cell apoptosis by scavenging radiation-induced excess ROS and up-regulates the inherent enzymatic antioxidants, thereby protecting the proliferation and migration of mucosal epithelial cells. In conclusion, this work not only provides proof-of-principle evidence for the oral radioprotection of FOH by blocking the “ROS storm”, but also provides an effective and easy-to-use hydrogel system for mucosal in situ administration.  相似文献   

16.
The valence and oxygen defect properties of cerium oxide nanoparticles (nanoceria) suggest that they may act as auto‐regenerative free radical scavengers. Overproduction of the free radical nitric oxide (NO) by the enzyme inducible nitric oxide synthase (iNOS) has been implicated as a critical mediator of inflammation. NO is correlated with disease activity and contributes to tissue destruction. The ability of nanoceria to scavenge free radicals, or reactive oxygen species (ROS), and inhibit inflammatory mediator production in J774A.1 murine macrophages is investigated. Cells internalize nanoceria, the treatment is nontoxic, and oxidative stress and pro‐inflammatory iNOS protein expression are abated with stimulation. In vivo studies show nanoceria deposition in mouse tissues with no pathogenicity. Taken together, it is suggested that cerium oxide nanoparticles are well tolerated in mice and are incorporated into cellular tissues. Furthermore, nanoceria may have the potential to reduce ROS production in states of inflammation and therefore serve as a novel therapy for chronic inflammation.  相似文献   

17.
Bortezomib (BTZ), a proteasome inhibitor, is clinically used for the treatment of multiple myeloma and mantle cell lymphoma via intravenous or subcutaneous administration. Since BTZ has limited intestinal permeability, in this study, solid lipid nanoparticles (SLNs) were selected as lipid carrier to improve the intestinal permeability of BTZ. The nanoparticles were prepared by hot oil-in-water emulsification method and characterized for physicochemical properties. Moreover, in situ single-pass intestinal perfusion technique was used for intestinal permeability studies. Mean particle size of the BTZ-loaded solid lipid nanoparticles (BTZ-SLNs) was 94.6?±?0.66?nm with a negative surface charge of –18?±?11?mV. The entrapment efficiency of the BTZ-SLNs was 68.3?±?3.7% with a drug loading value of 0.8?±?0.05%. Cumulative drug release (%) over 48?h, indicated a slow release pattern for nanoparticles. Moreover, the SEM image showed a spherical shape and uniform size distribution for nanoparticles. Also, FTIR analysis indicated that BTZ was successfully loaded in the SLNs. The results of the intestinal perfusion studies revealed an improved effective permeability for BTZ-SLNs with a Peff value of about threefold higher than plain BTZ solution.  相似文献   

18.
Although nanoparticle‐based drug delivery systems have been widely explored for tumor‐targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia‐associated resistance to radiation‐induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide 131I labeled human serum albumin (HSA)‐bound manganese dioxide nanoparticles (131I‐HSA‐MnO2) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME). Such 131I‐HSA‐MnO2 nanoparticles with suitable sizes during blood circulation show rather efficient tumor passive uptake owing to the enhanced permeability and retention effect, as well as little retention in other normal organs to minimize radiotoxicity. The acidic TME can trigger gradual degradation of MnO2 and thus decomposition of 131I‐HSA‐MnO2 nanoparticles into individual 131I‐HSA with sub‐10 nm sizes and greatly improves intratumoral diffusion. Furthermore, oxygen produced by MnO2‐triggered decomposition of tumor endogenous H2O2 would be helpful to relieve hypoxia‐associated RIT resistant for those tumors. As the results, the 131I‐HSA‐MnO2 nanoparticles appear to be a highly effective RIT agent showing great efficacy in tumor treatment upon systemic administration.  相似文献   

19.
Smart molecular probes that emit deep‐tissue penetrating photoacoustic (PA) signals responsive to the target of interest are imperative to understand disease pathology and develop innovative therapeutics. This study reports a self‐assembly approach to develop semiconducting macromolecular activatable probe for in vivo imaging of reactive oxygen species (ROS). This probe comprises a near‐infrared absorbing phthalocyanine core and four poly(ethylene glycol) (PEG) arms linked by ROS‐responsive self‐immolative segments. Such an amphiphilic macromolecular structure allows it to undergo an ROS‐specific cleavage process to release hydrophilic PEG and enhance the hydrophobicity of the nanosystem. Consequently, the residual phthalocyanine component self‐assembles and regrows into large nanoparticles, leading to ROS‐enhanced PA signals. The small size of the intact macromolecular probe is beneficial to penetrate into the tumor tissue of living mice, while the ROS‐activated regrowth of nanoparticles prolongs the retention along with enhanced PA signals, permitting imaging of ROS during chemotherapy. This study thus capitalizes on stimuli‐controlled self‐assembly of macromolecules in conjunction with enhanced heat transfer in large nanoparticles for the development of smart molecular probes for PA imaging.  相似文献   

20.
Short, single‐particle‐wide chains and complex networks of interconnected chains are easily self‐assembled from 13 nm Au nanoparticles by inducing a surface electrostatic dipolar moment in a controlled manner. Mann and co‐workers further demonstrate both experimentally and theoretically on p. 2553 that efficient surface plasmon coupling takes place in these extensive networks, thus opening a new bottom–up approach to subwavelength optical‐waveguiding devices. The left panel in the image shows isolated 13 nm Au nanoparticles; the back panel, short linear chains; the bottom panel, complex branched network of chains; and the right panel, a graphical rendering of optical spectroscopic properties during the self‐assembly process.  相似文献   

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