Ba2+-doping introduced piezoelectricity and efficient Ultrasound-Triggered bactericidal activity of brookite TiO2 nanorods.

Exploring highly efficient ultrasound-triggered catalysts is pivotal for various areas. Herein, we presented that Ba2+ doped brookite TiO2 nanorod (TiO2: Ba) with polarization-induced charge separation is a candidate. The replacement of Ba2+ for Ti4+ not only induced significant lattice distortion to induce polarization but also created oxygen vacancy defects for facilitating the charge separation, leading to high-efficiency reactive oxygen species (ROS) evolution in the piezo-catalytic processes. Furthermore, the piezocatalytic ability to degrade dye wastewater demonstrates a rate constant of 0.172 min-1 and achieves a 100 % antibacterial rate at a low dose for eliminating E. coli. This study advances that doping can induce piezoelectricity and reveals that lattice distortion-induced polarization and vacancy defects engineering can improve ROS production, which might impact applications such as water disinfection and sonodynamic therapy.

Hemostatic and Ultrasound-Controlled Bactericidal Silk Fibroin Hydrogel via Integrating a Perfluorocarbon Nanoemulsion.

Excessive blood loss and infections are the prominent risks accounting for mortality and disability associated with acute wounds. Consequently, wound dressings should encompass adequate adhesive, hemostatic, and bactericidal attributes, yet their development remains challenging. This investigation presented the benefits of incorporating a perfluorocarbon nanoemulsion (PPP NE) into a silk-fibroin (SF)-based hydrogel. By stimulating the ß-sheet conformation of the SF chains, PPP NEs drastically shortened the gelation time while augmenting the elasticity, mechanical stability, and viscosity of the hydrogel. Furthermore, the integration of PPP NEs improved hemostatic competence by boosting the affinity between cells and biomacromolecules. It also endowed the hydrogel with ultrasound-controlled bactericidal ability through the inducement of inner cavitation by perfluorocarbon and reactive oxygen species (ROS) generated by the sonosensitizer protoporphyrin. Ultimately, we employed a laparotomy bleeding model and a Staphylococcus aureus-infected trauma wound to demonstrate the first-aid efficacy. Thus, our research suggested an emulsion-incorporating strategy for managing emergency wounds.

Enhanced NOx absorption in flue gas by wet oxidation of red mud and phosphorus sludge.

The environmental problem caused by industrial emissions of NOx has been studied in the past dacades. In this study, red mud coupling with phosphorus sludge were used to enhance the solution to absorb NOx from the flue gas. Firstly, red mud reacted with the binder silicic acid in the phosphorus sludge, destroying the emulsion structure of the phosphorus sludge. Then, the P4 in the phosphorus sludge is completely released, and the P4 reacted with O2 in the flue gas to produce O3 and O. NO and NO2 contained in the flue gas reacted with the active O and O3 to produce high-valent NOx, such as NO3, N2O5. At last, the mixed slurry of red mud and phosphorus sludge absorbed the high-valent NOx, resulting in the formation of Ca5(PO4)3F along with HNO3. Using phosphorus sludge to produce O3 in the reaction process can reduce the production cost of O3 and achieve waste utilization. Meanwhile, the interaction between red mud and phosphorus sludge can promote phosphorus sludge to produce O3 and remove F- from phosphorus sludge, as well as avoid the problem of secondary pollution. This study should be helpful for red mud and phosphorus sludge utilization and flue gas denitration.

Near-Infrared Light-Excited Reactive Oxygen Species Generation by Thulium Oxide Nanoparticles.

Exploring materials that can absorb near-infrared (NIR) light to produce reactive oxygen species (ROS) is necessary for many fields. Herein we show that thulium oxide nanoparticles are viable for NIR-stimulated ROS generation. This property may be related to the unique energy levels, large absorption cross section, low fluorescence emission, and ∼10-3 s lifetime of the 3H4 state of Tm ions. We further demonstrate the impact of these nanoparticles on photodynamic therapy (PDT), in which impressive tumor inhibition was recorded after exposure to either a broadband halogen lamp or an 808 nm laser. Our results may provide insight into the areas of photocatalysis, pollution treatment, and fine chemical synthesis.

Catalytically Active CoFe2O4 Nanoflowers for Augmented Sonodynamic and Chemodynamic Combination Therapy with Elicitation of Robust Immune Response.

A hypoxic and acidic tumor microenvironment (TME) plays a significant role in cancer development through complex cellular signaling networks, and it is thus challenging to completely eradicate tumors via monotherapy. Here, PEGylated CoFe2O4 nanoflowers (CFP) with multiple enzymatic activities, serving as bioreactors responsive to TME cues, were synthesized via a typical solvothermal method for augmented sonodynamic therapy (SDT) and chemodynamic therapy (CDT) with elicitation of robust immune response. The CFP occupying multivalent elements (Co2+/3+, Fe2+/3+) exhibited strong Fenton-like and catalase-like activity. In another aspect, CFP itself is a brand-new sonosensitizer for high-performance SDT based on ultrasound-triggered electron (e-)/hole (h+) pair separation from the energy band with promptness and high efficiency. With efficient enrichment in tumorous tissue as revealed by magnetic resonance imaging, CPF could generate •OH for CDT relying on Fenton-like reactions. Moreover, catalase-mimicking CFP could react with endogenous H2O2 to generate molecular oxygen, and high O2 level may promote the production of 1O2 for SDT. What's more, the reactive oxygen species obtained from combined SDT/CDT could efficiently trigger immunogenic cell death through a synergistic therapy based on the elicitation of antitumor immunity with the aid of an immune checkpoint blockade for the sake of suppressing primary and distant tumors as well as lung metastasis. Taken together, this paradigm delivers useful insights for developing in-coming nanocomposites based on cobalt ferrite for cancer theranostics.

MnO2-capped silk fibroin (SF) nanoparticles with chlorin e6 (Ce6) encapsulation for augmented photo-driven therapy by modulating the tumor microenvironment.

Silk fibroin (SF), derived from Bombyx mori, is a category of fibrous protein with outstanding potential for applications in the biomedical and biotechnological fields. In spite of its many advantageous properties, the exploration of SF as a versatile nanodrug precursor for tumor therapy has still been restricted in recent years. Herein, a multifunctional SF-derived nanoplatform was facilely developed via encapsulating the photosensitizer chlorin e6 (Ce6) into MnO2-capped SF nanoparticles (NPs). SF@MnO2 nanocarriers were synthesized through a surface crystallization technique, using SF as a reductant and sacrificial template. Afterwards, Ce6 was covalently incorporated into the loose structure of the SF@MnO2 nanocarrier on the basis of adsorption to abundant peptide-binding sites. To modulate the tumor microenvironment (TME), SF@MnO2/Ce6 (SMC) NPs were capable of catalyzing the decomposition of H2O2 into O2, which can be converted into cytotoxic reactive oxygen species (ROS) during photodynamic therapy (PDT). Moreover, the MnO2 component was able to oxidize intracellular glutathione (GSH) into non-reducing glutathione disulfide (GSSG), and the consumption of GSH could significantly protect the local ROS from being reduced, which further augmented the therapeutic outcome of PDT. Via another angle, SMC NPs can produce strong hyperthermia under near-infrared (NIR) light activation, which was highly desirable for efficient photothermal therapy (PTT). Both in vitro and in vivo studies demonstrated the intense tumor inhibitory effects as a result of augmented PTT/PDT mediated by SMC NPs. We believe that this study may provide useful insights for employing SF-based nanocomposites for more medical applications in the near future.

Facile engineering of silk fibroin capped AuPt bimetallic nanozyme responsive to tumor microenvironmental factors for enhanced nanocatalytic therapy.

Background: Reactive oxygen species (ROS), as a category of highly reactive molecules, are attractive for eliminating tumor cells in situ. However, the intrinsic tumor microenvironment (TME) always compromises treatment efficacy. In another aspect, silk fibroin (SF), as a category of natural biomacromolecules, is highly promising for synthesis of metallic nanocrystals via biomineralization. Methods: As a proof-of-concept study, AuPt bimetallic nanozyme derived from bioinspired crystallization of chloroauric acid and chloroplatinic acid was facilely developed in the presence of silk fibroin (SF). Antitumor effects caused by the as-synthesized AuPt@SF (APS) nanozyme were demonstrated in 4T1 tumor cells in vitro and xenograft tumor models in vivo. Results: APS nanozyme can decompose glucose to constantly supply H2O2 and deplete intracellular glutathione (GSH). APS nanozyme can simultaneously convert adsorbed O2 and endogenic H2O2 into superoxide radicals (•O2-) and hydroxyl radical (•OH), respectively, upon highly efficient catalytic reaction. Subsequently, these cytotoxic ROS cause irreversible damage to the cell membrane, nucleic acid and mitochondria of tumors. Upon fluorescence/photoacoustic (FL/PA)-imaging guidance, remarkable tumor damage based on the current nanoplatform was confirmed in vivo. Conclusion: The objective of our investigation is to supply more useful insights on the development of SF-based nanocatalysts, which are specifically responsive to TME for extremely efficient tumor theranostics.

Facile synthesis of hollow mesoporous nickel sulfide nanoparticles for highly efficient combinatorial photothermal-chemotherapy of cancer.

Traditional techniques for the synthesis of nickel sulfide (NiS) nanoparticles (NPs) always present drawbacks of morphological irregularity, non-porous structure and poor long-term stability, which are extremely unfavorable for establishing effective therapeutic agents. Here, a category of hollow mesoporous NiS (hm-NiS) NPs with uniform spherical structure and good aqueous dispersity were innovatively developed based on a modified solvothermal reaction technique. Upon the successful synthesis of hm-NiS NPs, dopamine was seeded and in situ polymerized into polydopamine (PDA) on the NP surface, followed by functionalization with thiol-polyethylene glycol (SH-PEG) and encapsulation of the chemotherapeutic drug, doxorubicin (DOX), to form hm-NiS@PDA/PEG/DOX (NiPPD) NPs. The resultant NiPPD NPs exhibited a decent photothermal response and stability, attributed to the optical absorption of the hm-NiS nanocore and PDA layer in the near-infrared (NIR) region. Furthermore, stimulus-responsive drug release was achieved under both acidic pH conditions and NIR laser irradiation, owing to the protonation of -NH2 groups in the DOX molecules and local thermal shock, respectively. Lastly, a strong combinatorial photothermal-chemotherapeutic effect was demonstrated for tumor suppression with minimal systemic toxicity in vivo. Collectively, this state-of-the-art paradigm may provide useful insights to deepen the application of hm-NiS NPs for disease management and precision medicine.

Biomimetic CoO@AuPt nanozyme responsive to multiple tumor microenvironmental clues for augmenting chemodynamic therapy.

Chemodynamic therapy (CDT), an emerging therapeutic strategy, has been recently exploited for in situ treatment through Fenton or Fenton-like reactions to generate cytotoxic reactive oxygen species (ROS). However, current systems rely significantly on the high local oxygen levels and strongly acidic conditions (pH = 3.0-5.0). Simultaneously, the produced ROS can be rapidly consumed by intracellular glutathione (GSH) in the electron transport chain. Herein, an original and biomimetic CoO@AuPt nanocatalyst was prepared based on the assembly of Au and Pt nanoparticles (NPs) on the surface of hollow CoO nanocapsules. The as-synthesized nanozyme exhibits extremely high stability under physiological conditions, whereas it undergoes spontaneous disintegration in the unique tumor microenvironment (TME). Subsequently, the decomposition products can catalyze a cascade of biochemical reactions to produce abundant ROS without any external stimuli. Thus, the present nanoplatform can increase intracellular ROS levels through continuous supply of H2O2, relief of local hypoxia and depletion of GSH, which result in remarkable and specific tumor damage both in vitro and in vivo. The findings of this study highlight the promising potential of CoO@AuPt nanocatalyst as a TME-responsive CDT nanomagnet for highly efficient tumor therapy.

Biomineralization-inspired Crystallization of Manganese Oxide on Silk Fibroin Nanoparticles for in vivo MR/fluorescence Imaging-assisted Tri-modal Therapy of Cancer.

Regenerated silk fibroin (SF) is a type of natural biomacromolecules with outstanding biocompatibility and biodegradability. However, stimulus-responsive SF-based nanocomplex has seldom been reported for application in tumor diagnosis and therapy. Methods: As a proof-of-concept study, a multifunctional SF@MnO2 nanoparticle-based platform was strategically synthesized using SF as a reductant and a template via a biomineralization-inspired crystallization process in an extremely facile way. Because of their mesoporous structure and abundant amino and carboxyl terminal residues, SF@MnO2 nanoparticles were co-loaded with a photodynamic agent indocyanine green (ICG) and a chemotherapeutic drug doxorubicin (DOX) to form a SF@MnO2/ICG/DOX (SMID) nanocomplex. Results: The obtained product was highly reactive with endogenous hydrogen peroxide (H2O2) in tumor microenvironment, which was decomposed into O2 to enhance tumor-specific photodynamic therapy (PDT). Moreover, SMID nanocomplex produced a strong and stable photothermal effect upon near-infrared (NIR) irradiation for photothermal therapy (PTT) owing to the distinct photothermal response of SF@MnO2 and stably conjugated ICG. The concurrent NIR fluorescence and magnetic resonance (MR) imaging in vivo both indicated effective tumor-specific enrichment of SMID nanoparticles via enhanced permeability and retention (EPR) effect. Animal studies further verified that SMID nanoparticles remarkably improved tumor inhibitive efficacy through combination PTT/PDT/chemotherapy with minimal systemic toxicity or adverse effect. Conclusion: This study demonstrated the promising potential of SF-based nanomaterial to address some of the key challenges in cancer therapy due to unfavorable tumor microenvironment for drug delivery.

Rapid prototyping of Nanoroughened polydimethylsiloxane surfaces for the enhancement of immunomagnetic isolation and recovery of rare tumor cells.

Traditional immunomagnetic assays for the isolation and recovery of circulating tumor cells (CTCs) usually require sophisticated device or intense magnetic field to simultaneously achieve high capture efficiency and high throughout. In this study, a simple microfluidic chip featured with nanoroughened channel substrate was developed for effectively capture and release of CTCs based on an immunomagnetic chip-based approach. The nanoroughened substrate aims to increase the cell-surface contact area, facilitate the immobilization of magnet particles (MPs) and accommodate cell attachment tendency. Hep3B tumor cells were firstly conjugated with MPs that were functionalized with anti-EpCAM. Comparing with the flat channel, MPs modified tumor cells can be more effectively captured on nanoroughened substrate at the presence of the magnetic field. Upon the removal of magnetic field, these captured cells can be released from the device and collected for further analysis. Under the optimum operating conditions, the capture efficiency of tumor cells was obtained as high as ~90% with a detection limit of 10 cell per mL. Additionally, recovery rates of trapped tumor cells at various densities all exceeded 90% and their biological potencies were well retained by investigating the cell attachment and proliferation. Therefore, the present approach may potentially be used in clinical CTC analysis for cancer diagnosis and prognosis as well as the fundamental understanding of tumor metastasis.

Indocyanine green-modified hollow mesoporous Prussian blue nanoparticles loading doxorubicin for fluorescence-guided tri-modal combination therapy of cancer.

Hollow mesoporous structures with interior cavities and expanded surface area have attracted considerable interest as drug delivery systems. In this study, a multifunctional nanotheranostic agent was developed by conjugating indocyanine green (ICG) and loading doxorubicin (DOX) onto the surfaces or within the cavities of hollow mesoporous Prussian blue (HMPB) nanoparticles, known as HMPB@PEI/ICG/DOX or simply HPID NPs, which were investigated as phototheranostic agents for in vivo fluorescence imaging and light-induced chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT). These original HPID NPs exhibited strong near infrared (NIR) absorbance, reactive oxygen species (ROS) yield, and controlled chemotherapeutic drug release behavior. After intravenous injection of HPID NPs, highly efficient solid tumor ablation effects were observed in 4T1 tumor-bearing mouse models under NIR laser irradiation. Additionally, there was insignificant low-term toxicity or damage to normal tissues, as evidenced by histopathological and hemocompatibility analyses, suggesting that this agent has reliable biosafety for systemic applications. Taken together, the results of this study suggest that HPID NPs can produce tumor-specific and stimuli-triggered theranostic effects under tri-modal combination therapy. These HPID NPs advantageously provide traceable accumulation and activation and therefore could be a capable mediator in nanomedicines for eliminating solid tumors.

Phase-Change Material Packaged within Hollow Copper Sulfide Nanoparticles Carrying Doxorubicin and Chlorin e6 for Fluorescence-Guided Trimodal Therapy of Cancer.

Environmental stimuli, including pH, light, and temperature, have been utilized for activating controlled drug delivery to achieve efficient antitumor therapeutics while minimizing undesirable side effects. In this study, a multifunctional nanoplatform based on hollow mesoporous copper sulfide nanoparticles (H-CuS NPs) was developed by loading the interior cavity of the NPs with a drug-loaded phase-change material (PCM, 1-tetradecanol). Doxorubicin (DOX) and chlorin e6 (Ce6) were selected as the model chemotherapeutic drug and photosensitizer, respectively, which were encapsulated in H-CuS NPs via the PCM to form H-CuS@PCM/DOX/Ce6 (HPDC) NPs. When exposed to near infrared laser irradiation, this nanocomplex could produce a strong photothermic effect and thus induce the controlled release of DOX and Ce6 from the melting PCM. Subsequently, the DOX-mediated chemotherapeutic effect and Ce6-mediated photodynamic effect further contributed to enhanced tumor eradication. The efficacy of this multimodal cancer treatment combining chemo-, photothermal, and photodynamic therapies was systematically evaluated both in vitro and in vivo using a 4T1 mouse mammary tumor cell line and a mouse model bearing breast cancer. Moreover, this nanoplatform exhibited minimal systemic toxicity and good hemocompatibility and may provide an effective strategy for the delivery of multiple therapeutic agents and application of multimodal cancer treatments.

Indocyanine Green-Conjugated Magnetic Prussian Blue Nanoparticles for Synchronous Photothermal/Photodynamic Tumor Therapy.

Indocyanine green (ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor therapy is associated with their instability in aqueous conditions and rapid clearance from blood circulation, which causes insufficient bioavailability at the tumor site. Herein, we conjugated ICG molecules with Prussian blue nanoparticles enclosing a Fe3O4 nanocore, which was facilitated by cationic polyethyleneimine via electrostatic adsorption. The nanocarrier-loaded ICG formed stable aggregates that enhanced cellular uptake and prevented fluorescence quenching. Moreover, the strong superparamagnetism of the Fe3O4 core in the obtained nanocomposites further improved cellular internalization of the drugs guided by a localized magnetic field. The therapeutic efficacy of this nanoplatform was evaluated using tumor models established in nude mice, which demonstrated remarkable tumor ablation in vivo due to strong photothermal/photodynamic effects. This study provides promising evidence that this multifunctional nanoagent might function as an efficient mediator for combining photothermal and photodynamic cancer therapy.

Light-activatable Chlorin e6 (Ce6)-imbedded erythrocyte membrane vesicles camouflaged Prussian blue nanoparticles for synergistic photothermal and photodynamic therapies of cancer.

Multiple therapeutic modalities, such as photodynamic (PDT) and photothermal (PTT) therapies, have been jointly applied to produce a synergistic effect for tumor eradication based on the hyperthermia and generation of reactive oxygen species (ROS) mediated by photoactive agents. Effective delivery of highly efficient photosensitizers and photothermal agents is the key for combination of PDT/PTT. Herein, we propose a strategy to functionalize Prussian blue (PB) nanoparticles (NPs) with Chlorin e6 (Ce6)-imbedded erythrocyte membrane vesicles. This nanoplatform can address the major issues of these two capable photoactive agents, such as limited biocompatibility, lack of functional chemical groups, and poor bioavailability due to rapid blood clearance or self-aggregation. Specifically, PB NPs were packaged within Ce6-imbedded erythrocyte membrane vesicles, named as PB@RBC/Ce6 NPs, to take advantage of both biological functions of natural erythrocyte membranes and the unique physicochemical properties of synthetic nanoagents. Compared to bare PB NPs or free Ce6, PB@RBC/Ce6 NPs exhibited considerably enhanced cellular uptake and accumulation in tumoral tissues. Moreover, the PB@RBC/Ce6 NP-mediated PDT/PTT combination therapies produced a notable effect in boosting the necrosis and late apoptosis of tumor cells in vitro, and further showed a synergistic therapeutic effect against an orthotopic tumor model in vivo.

Injectable and Natural Humic Acid/Agarose Hybrid Hydrogel for Localized Light-Driven Photothermal Ablation and Chemotherapy of Cancer.

The injection of theranostic drug-laden hydrogels into subcutaneous tumors has proven to be a promising strategy to achieve precise local tumor eradication. Humic acid, a natural product of biochemical decomposition of animal and plant residues, abundantly exists in soils, peats, oceans, etc. In this study, a robust injectable thermoresponsive agarose hydrogel incorporating sodium humate (SH) and doxorubicin (DOX) was constructed as a unique agent for tumor management based on the combined chemo-photothermal therapeutic effect. SH, which strongly absorbs near-infrared (NIR) light, can efficiently convert light energy into thermal energy, induce local hyperthermia and subsequently trigger sustained drug release from the complex of the SH/DOX@hydrogel through a typical gel-sol transition, resulting in enhanced cellular uptake of therapeutic drugs. Moreover, intratumoral injection of the SH/DOX@hydrogel resulted in a simultaneous chemo-photothermal therapeutic effect against solid tumors under NIR laser irradiation, which may collectively prevent tumor recurrence. In addition, the SH/DOX@hydrogel exhibited ultralow systemic toxicity as demonstrated using an animal model. This work provides a promising attempt to develop a low-cost, light-responsive hydrogel for precise tumor therapy, which may also incorporate extra theranostic modules as an advanced platform for the treatment of cancer or other critical diseases.