Search

Abstract Systematical and critical learning from industrial catalysis will bring inspiration for emerging nanocatalytic medicine, but the relevant knowledge is quite limited so far. In this review, we briefly summarize representative catalytic reactions and corresponding catalysts in industry, and then distinguish the similarities and differences in catalytic reactions between industrial and medical applications in support of critical learning, deep understanding, and rational designing of appropriate catalysts and catalytic reactions for various medical applications. Finally, we summarize/outlook the present and potential translation from industrial catalysis to nanocatalytic medicine. This review is expected to display a clear picture of nanocatalytic medicine evolution.

Chronic systemic inflammation in obesity-associated type 2 diabetes (T2D) is a key inducing factor of insulin resistance (IR). Hydrogen molecule (H2) has been proved to be a safe and effective anti-inflammatory agent, but conventional H2 administration methods cannot provide a high dosage and a long duration of H2 treatment in IR-related tissues and thus lead to limited therapeutic efficacies. We here propose a new strategy of controlled H2 release to match the time window of gastric emptying for maximizing the bioavailability and therapeutic outcome of H2. This work enhances the hydrolysis rate of Zn by constructing a Zn-Fe primary-battery micro-/nano-structure, and the H2-releasing rate is adjusted by tuning the ratio of Zn to Fe. The Zn-Fe micro-/nano-structure is orally administrated once daily to alleviate obesity-associated T2D in a leptin-deficient (ob/ob) mouse model. The H2 generation time of the Zn-Fe primary-battery micro-/nano-structure with the Fe/Zn ratio of 1:100 in gastric acid is about 3 h, just matching with the time window of gastric emptying in mice. In vivo monitoring results show that H2 generated by Zn-Fe micro-/nano-structure in stomach can effectively accumulate in major IR-sited tissues including liver, adipose tissue, and skeletal muscle at a high dose for a relatively long time compared to H2-rich water drinking. Oral administration of Zn-Fe micro-/nano-structure at 200 mg/kg body weight has realized an efficient IR improvement and remarkably ameliorated systemic inflammation in ob/ob mice. In addition, a high-dose administration of Zn-Fe shows no visible toxicity in mice. This work provides a new strategy to maximize the outcome of hydrogen therapy.

Abstract The senescence microenvironment, which causes persistent inflammation and loss of intrinsic regenerative abilities, is a main obstacle to effective tissue repair in elderly individuals. In this work, we find that local H2 supply can remodel the senescence microenvironment by anti-inflammation and anti-senescence effects in various senescent cells from skeletally mature bone. We construct a H2-releasing scaffold which can release high-dosage H2 (911 mL/g, up to 1 week) by electrospraying polyhydroxyalkanoate-encapsulated CaSi2 nanoparticles onto mesoporous bioactive glass. We demonstrate efficient remodeling of the microenvironment and enhanced repair of critical-size bone defects in an aged mouse model. Mechanistically, we reveal that local H2 release alters the microenvironment from pro-inflammation to anti-inflammation by senescent macrophages repolarization and secretome change. We also show that H2 alleviates the progression of aging/injury-superposed senescence, facilitates the recruitment of endogenous cells and the preservation of their regeneration capability, thereby creating a pro-regenerative microenvironment able to support bone defect regeneration.

In this paper, we first show that the $ p $-adic version of maximal function $ \mathcal{M}_{L\log L}^{p} $ is equivalent to the maximal function $ \mathcal{M}^{p}(\mathcal{M}^{p}) $ and that the class of functions for which the maximal commutators and the commutator with the $ p $-adic version of maximal function or the maximal sharp function are bounded on the $ p $-adic vector spaces are characterized and proved to be the same. Moreover, new pointwise estimates for these operators are proved.

Abstract Tumor heterogeneity makes routine drugs difficult to penetrate solid tumors, limiting their therapy efficacies. Based on high tissue penetrability of hydrogen molecules (H2) and ultrasound (US) and the immunomodulation effects of H2 and lactic acid (LA), this work proposes a novel strategy of US‐driven piezoelectrocatalytic tumor immunoactivation for high‐efficacy therapy of deep tumors by piezoelectrocatalytic hydrogen generation and LA deprivation. A kind of US‐responsive piezoelectric SnS nanosheets (SSN) is developed to realize US‐triggered local hydrogen production and simultaneous LA deprivation in deep tumors. The proof‐of‐concept experiments which are executed on an orthotopic liver cancer model have verified that intratumoral SSN‐medicated piezoelectrocatalytically generated H2 liberates effector CD8+ T cells from the immunosuppression of tumor cells through down‐regulating PD‐L1 over‐expression, and simultaneous LA deprivation activates CD8+ T cells by inhibiting regulatory T cells, efficiently co‐activating tumor immunity and achieving a high outcome of liver tumor therapy with complete tumor eradication and 100% mice survival. The proposed strategy of US‐driven piezoelectrocatalytic tumor immunoactivation opens a safe and efficient pathway for deep tumor therapy.

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, 89Zr-PCurNP M10 with the diameter between 5 and 8 nm, is found to be 1.7 times and 1.8 times higher than the accumulation of 89Zr-PCurNP M29 (20–50 nm) and M40 (20–50 nm) as revealed by PET imaging. Furthermore, serum creatinine analysis, kidney tissues histology, and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI. Herein, PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

Hydrogenation is a treatment for chronic inflammation caused by high glucose levels in diabetic ulcers, However, current therapies have limitations. Here, the authors report on the creation of a visible light photocatalytic agent which depletes glucose in the wound and generates hydrogen to aid in diabetic wound healing.

Engineering biomaterials to meet specific biomedical applications raises high requirements of mechanical performances, and simultaneous strengthening and toughening of polymer are frequently necessary but very challenging in many cases. In this work, we propose a new concept of nanoconcrete welding polymer chains, where mesoporous CaCO3 (mCaCO3) nanoconcretes which are composed of amorphous and nanocrystalline phases are developed to powerfully weld polymer chains through siphoning-induced occlusion, hydration-driven crystallization and dehydration-driven compression of nanoconcretes. The mCaCO3 nanoconcrete welding technology is verified to be able to remarkably augment strength, toughness and anti-fatigue performances of a model polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-based porous membrane. Mechanistically, we have revealed polymer-occluded nanocrystal structure and welding-derived microstress which is much stronger than interfacial Van der Waals force, thus efficiently preventing the generation of microcracks and repairing initial microcracks by microcracks-induced hydration, crystallization and polymer welding of mCaCO3 nanoconcretes. Constructed porous membrane is used as wound dressing, exhibiting a special nanoplates-constructed surface topography as well as a porous structure with plentiful oriented, aligned and opened pore channels, improved hydrophilicity, water vapor permeability, anti-bacterial and cell adherence, in support of wound healing and skin structural/functional repairing. The proposed nanoconcrete-welding-polymer strategy breaks a new pathway for improving the mechanical performances of polymers.

Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side effects. Unfortunately, nowadays the targeting efficiency of nanomedicine toward tumor is still quite limited and far from clinical requirements. In this work, we develop an innovative peptide-based nanoparticle to realize light-triggered nitric oxide (NO) release and structural transformation for enhanced intratumoral retention and simultaneously sensitizing photodynamic therapy (PDT). The designed nanoparticle is self-assembled from a chimeric peptide monomer, TPP-RRRKLVFFK-Ce6, which contains a photosensitive moiety (chlorin e6, Ce6), a β-sheet-forming peptide domain (Lys-Leu-Val-Phe-Phe, KLVFF), an oligoarginine domain (RRR) as NO donor and a triphenylphosphonium (TPP) moiety for targeting mitochondria. When irradiated by light, the constructed nanoparticles undergo rapid structural transformation from nanosphere to nanorod, enabling to achieve a significantly higher intratumoral accumulation by 3.26 times compared to that without light irradiation. More importantly, the conversion of generated NO and reactive oxygen species (ROS) in a light-responsive way to peroxynitrite anions (ONOO−) with higher cytotoxicity enables NO to sensitize PDT in cancer treatment. Both in vitro and in vivo studies demonstrate that NO sensitized PDT based on the well-designed transformable nanoparticles enables to eradicate tumors efficiently. The light-triggered transformable nanoplatform developed in this work provides a new strategy for enhanced intratumoral retention and improved therapeutic outcome.

Abstract Background Photothermal therapy (PTT) frequently cause thermal resistance in tumor cells by inducing the heat shock response, limiting its therapeutic effect. Hydrogen sulfide (H2S) with appropriate concentration can reverse the Warburg effect in cancer cells. The combination of PTT with H2S gas therapy is expected to achieve synergistic tumor treatment. Methods Here, sulourea (Su) is developed as a thermosensitive/hydrolysable H2S donor to be loaded into Pd nanocubes through in-depth coordination for construction of the Pd-Su nanomedicine for the first time to achieve photo-controlled H2S release, realizing the effective combination of photothermal therapy and H2S gas therapy. Results The Pd-Su nanomedicine shows a high Su loading capacity (85 mg g−1), a high near-infrared (NIR) photothermal conversion efficiency (69.4%), and NIR-controlled H2S release by the photothermal-triggered hydrolysis of Su. The combination of photothermal heating and H2S produces a strong synergetic effect by H2S-induced inhibition of heat shock response, thereby effectively inhibiting tumor growth. Moreover, high intratumoral accumulation of the Pd-Su nanomedicine after intravenous injection also enables photothermal/photoacoustic dual-mode imaging-guided tumor treatment. Conclusions The proposed NIR-responsive heat/H2S release strategy provides a new approach for effective cancer therapy. Graphic abstract

Nanoparticles have been used to reduce the toxicity associated with chemotherapeutic agents. Here, the authors report a Z-scheme SnS1.68-WO2.41 nanocatalyst for photocatalytic generation of oxidative holes and hydrogen molecules for drug-free therapeutic strategy.

Abstract The development of stimuli‐responsively degradable porous carriers for both controlled drug release and high biosafety is vitally important to their clinical translation, but still challenging at present. A new type of porphyrin–iron metal organic framework (Fe‐MOF) nanocrystals is engineered here as acid‐degradable drug carrier and hydrogen donor by the coordination between porphyrin and zero‐valence Fe atom. Fe‐MOF nanocrystals exhibit excellent acid‐responsive degradation for H2 generation and simultaneous release of the loaded drug for combined hydrogen‐chemotherapy of cancer multidrug resistance (MDR) and metastasis and for local hydrogen eradication of the off‐target induced toxic side effects of the drug to normal cells/tissues. Mechanistically, released H2 assists chemotherapeutic drug to efficiently inhibit cancer metastasis by immunoactivating intratumoral M1‐phenotype macrophages and consequently downregulating the expression of metastasis‐related matrix metalloproteinase‐2 (MMP‐2) and can also downregulate the expressions of both P‐glycoprotein (P‐gp) protein and adenosine triphosphate (ATP) in MDR cancer cells to sensitize chemotherapeutic drug for enhanced damage to mitochondria and DNA. High anti‐MDR/antimetastasis efficacies and high biocompatibility endow Fe‐MOF nanocrystals and the Fe‐MOF‐based nanomedicine with high potential for clinical translation.

In this paper, we give characterization of a p-adic version of Lipschitz spaces in terms of the boundedness of commutators of maximal function in the context of the p-adic version of Lebesgue spaces and Morrey spaces, where the symbols of the commutators belong to the Lipschitz spaces. A useful tool is a Lipschitz norm involving the John-Nirenberg-type inequality for homogeneous Lipschitz functions, which is new in the p-adic field context.

In this paper, we establish the sharp constant for q-analogus of Hausdorff operators on central q-Morrey spaces. As applications, the sharp constants for the q-analogus of Hardy operator and its dual operator, the q-analogue of Hardy-Littlewood-Pólya operator, and the q-analogue of Hilbert operator on central q-Morrey spaces are deduced.

Abstract The integration of biomaterials with cells for high overall performances is vitally important in tissue engineering, as scaffold‐free cell sheet lacks enough mechanical performance and cell viability while cell‐free scaffold possesses limited biological functions. In this study, we propose a new strategy to strengthen cell sheets and enhance cell activity for accelerating wound healing based on a novel sandwich structure of cell sheet‐plasmid@membrane‐cell sheet (CpMC). Specifically, the CpMC contains two adipose‐derived stem cell (ADSC) sheets on outer surfaces and an electrospun gelatin/chitosan nanofibrous membrane (NFM) encapsulating vascular endothelial growth factor (VEGF) plasmids in between. The physicochemical properties of NFM including swelling, stiffness, strength, elasticity, and biodegradation can be tailored by simply adjusting the ratio between gelatin and chitosan to be 7:3 which is optimal for most effectively supporting ADSCs adhesion and proliferation. The swelling/biodegradation of NFM mediates the sustained release of encapsulated VEGF plasmids into adjacent ADSCs, and NFM assists VEGF plasmids to promote the differentiation of ADSCs into endothelial, epidermal, and fibroblast cells, in support of the neoangiogenesis and regeneration of cutaneous tissues within 2 weeks. The proposed membrane‐supporting cell sheet strategy provides a new route to tissue engineering, and the developed CpMC demonstrates a high potential for clinical translation.

Abstract Gas therapy, an emerging cancer treatment method of inflammation‐related diseases, has recently received substantial attention. The rapid advances in nanomedicine and nanotechnology have made gas precision treatment possible through tumor targeted delivery and controlled release of therapeutic agents. Single therapeutic is often inevitably accompanied with limited therapy efficacy. Gas therapy combined with other treatment methods can sensitize different therapy modes to augment cancer therapy. Understanding the mechanism through which gas enhances other therapeutic modalities will enable the design of reasonable strategies for clinical cancer therapy. In this review, we summarize novel gas‐based nanomedicines, focusing on gas‐based nanomedicine carriers, along with the release of gas molecules and the mechanisms of gas enhanced therapy. We describe the design of novel gas‐releasing nanoplatforms and the underlying synergistic mechanisms against cancer. Moreover, we describe the current challenges and outlook for future prospects in novel gas‐based nanomedicines for gas therapy in cancer.

Abstract Background To improve the outcome of cancer treatment, the combination of multiple therapy models has proved to be effective and promising. Gas therapy (GT) and chemodynamic therapy (CDT), mainly targeting the mitochondrion and nucleus, respectively, are two emerging strategy for anti-cancer. The development of novel nanomedicine for integrating these new therapy models is greatly significant and highly desired. Methods A new nanomedicine is programmed by successive encapsulation of MnO2 nanoparticles and iron carbonyl (FeCO) into mesoporous silica nanoparticle. By decoding the nanomedicine, acidity in the lysosome drives MnO2 to generate ROS, ·OH among which further triggers the decomposition of FeCO into CO, realizing the effective combination of chemodynamic therapy with gas therapy for the first time. Results Acidity in the TEM drives MnO2 to generate ROS, ∙OH among which further triggers the decomposition of FeCO into CO, realizing the effective combination of CDT and CDGT. The co-released ROS and CO do damage to DNA and mitochondria of various cancer cells, respectively. The mitochondrial damage can effectively cut off the ATP source required for DNA repair, causing a synergetic anti-cancer effect in vitro and in vivo. Conclusions The combination of CDT and CDGT causing a synergetic anti-cancer effect in vitro and in vivo. The proposed therapy concept and nanomedicine designing strategy might open a new window for engineering high-performance anti-cancer nanomedicine.

In this paper, we study the sharp bounds for the generalized m-linear n-dimensional p-adic Hardy-Littlewood-Pólya operator on central and noncentral p-adic Morrey spaces with power weight. As an application, the sharp bounds for the p-adic Hardy-Littlewood-Pólya operator on corresponding Morrey spaces are obtained. These results generalize substantially some well-known results.

In this paper, we obtain the sharp bound for fractional conjugate Hardy operator on higher-dimensional product spaces from L1ℝn1×⋯×ℝnm to the space wLQℝn1×⋯×ℝnm and Lpℝn1×⋯×ℝnm to the space Lqℝn1×⋯×ℝnm. More generally, the operator norm of the fractional Hardy operator on higher-dimensional product spaces from LPℝn1×⋯×ℝnm to LQIℝn1×⋯×ℝnm is obtained.

The tracking and targeted release of multi-agents to cooperatively treat cancer is a developing and evolving field. Here, the authors demonstrate the anticancer effects of cubic Pd hydride nanocrystals with photoacoustic imaging properties that can release hydrogen under an NIR trigger and have photothermal effects.

The dc-link voltage balance and reactive power equilibrium of the cascaded H-bridge rectifier (CHBR) are the prerequisites for the safe and stable operation of the system. However, the conventional PI (Proportional-Integral) control strategy only puts emphasis on the CHBR dc-link voltage balance without taking into account its reactive power equilibrium under capacitive and inductive working conditions. For this reason, this paper has proposed a novel control strategy for the CHBR that can not only balance dc-link voltage, but also achieve reactive power equilibrium and eliminate the coupling effect between the voltage-balancing controller (VBC) and original system controller (OSC). The control strategy can achieve dc-link voltage balance and the reactive power equilibrium of the CHBR through modifying the active duty cycle by closed loop control, and adjusting the reactive duty cycle relatively according to the modifiable amount of the active duty cycle. Moreover, the strategy can eliminate the coupling effect between the VBC and OSC by the open loop control modification of the active and reactive duty cycle of any H-bridge module in CHBR. Simulations and experiments have shown that the proposed control strategy is feasible and effective in performing the CHBR dc-link voltage balance and reactive power equilibrium under all working conditions and load variations.

In this paper, we study the sharp bound for m-linear n-dimensional p-adic Hausdorff operators on central and noncentral p-adic Morrey spaces with power weights, and we also give the sharp bonds of p-adic Hausdorff operators on central and noncentral p-adic Morrey spaces. Moreover, this is a generalization of the previous results. [ABSTRACT FROM AUTHOR]