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Matrix metalloproteinase-2 (MMP-2)-responsive nanodrug vehicles have garnered significant attention as antitumor drug delivery systems due to the extensive research on matrix metalloproteinases (MMPs) within the tumor extracellular matrix (ECM). These nanodrug vehicles exhibit stable circulation in the bloodstream and accumulate specifically in tumors through various mechanisms. Upon reaching tumor tissues, their structures are degraded in response to MMP-2 within the ECM, resulting in drug release. This controlled drug release significantly increases drug concentration within tumors, thereby enhancing its antitumor efficacy while minimizing side effects on normal organs. This review provides an overview of MMP-2 characteristics, enzyme-sensitive materials, and current research progress regarding their application as MMP-2-responsive nanodrug delivery system for anti-tumor drugs, as well as considering their future research prospects. In conclusion, MMP-2-sensitive drug delivery carriers have a broad application in all kinds of nanodrug delivery systems and are expected to become one of the main means for the clinical development and application of nanodrug delivery systems in the future., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2024. Published by Elsevier B.V.)

Various metal oxide nanomaterials have been widely used as carriers to prepare pH-sensitive nanomedicines to respond to the acidic tumor microenvironment promoting antitumor efficiency. Herein, we used zinc oxide nanoparticles (ZnO NPs) as metal oxide nanomaterial coated with low-molecular-weight heparin (LMHP) and doxorubicin (DOX) complex (LMHP-DOX) to prepare ZnO-LD NPs for controllable pH-triggered DOX release on the targeted site. Our results indicated that the released DOX from ZnO-LD NPs was pH-sensitive. The oxygen produced by ZnO-LD NPs in H 2 O 2 solution was observed in in vitro experiment. The ZnO-LD NPs entered into both PC-3M and 4T1 tumor cells via clathrin-mediated endocytosis and micropinocytosis pathway. The intracellular reactive oxygen species (ROS) generated by ZnO-LD NPs could significantly increase the caspase 3/7 level, leading to tumor cell apoptosis. The in vitro and in vivo antitumor activity was confirmed in PC-3M and 4T1 cell lines or tumor-bearing mice models. The in vivo and in vitro tumor images via second-order nonlinearity of ZnO-LD NPs indicated that ZnO-LD NPs could penetrate deep into the tumor tissues. Therefore, the ZnO-LD NPs developed in our study could provide an efficient approach for the preparation of pH-sensitive nano delivery systems suitable for tumor therapy and imaging.

As a traditional treatment for papillary thyroid cancer (PTC), surgical resection of diseased tissues often brings lots of inconveniences to patients, and the tumor recurrence and metastasis are difficult to avoid. Herein, we developed a gene and photothermal combined therapy nanosystem based on a polypyrrole (Ppy)-poly(ethylene imine)-siILK nanocomplex (PPR ILK ) to achieve minimally invasive ablation and lymphatic metastasis inhibition in PTC simultaneously. In this system, gelatin-stabilized Ppy mainly acted as a photothermal- and photoacoustic (PA)-responsive nanomaterial and contributed to its well-behaved photosensitivity in the near-infrared region. Moreover, gelatin-stabilized Ppy possessed a charge reversal function, facilitating the tight conjunction of siILK gene at physiological pH (7.35-7.45) and its automatic release into acidic lysosomes (pH 4.0-5.5); the proton sponge effect generated during this process further facilitated the escape of siILK from lysosomes to the cytoplasm and played its role in inhibiting PTC proliferation and lymphatic metastasis. With the guidance of fluorescence and PA bimodal imaging, gene delivery and Ppy location in tumor regions could be clearly observed. As a result, tumors were completely eradicated by photothermal therapy, and the recurrences and metastases were obviously restrained by siILK.

Hypoxia in a solid tumor microenvironment (TME) can lead to the overexpression of hypoxia-inducible factor-1α (HIF-1α), which correlates to tumor metastasis. Reactive oxygen species (ROS) induced tumor cell apoptosis is becoming a promising method in tumor treatment. Currently, the ROS generating systems, e.g., photodynamic treatment and sonodynamic treatment, highly depend on oxygen (O 2 ) in the tumor microenvironment (TME). However, the level of O 2 in TME is too low to produce enough ROS. Herein, we developed an ultrasmall DSPE-PEG 2000 coated barium titanate nanoparticle (P-BTO) for tumor treatment based on ultrasound triggered piezocatalysis and water splitting. Interestingly, irradiated by ultrasound, the surface of ultasmall P-BTO nanoparticles produced imbalance charges, which induced a cascade of redox reaction processes to simultaneously generate ROS and O 2 , the latter one was hardly generated in large-sized barium titanate nanoparticles. The as-synthesized P-BTO reached the highest accumulation in the tumor site at 4 h after intravenous injection. The results showed that the produced O 2 significantly alleviated the hypoxia of TME to down-regulate the expression of HIF-1α, and the produced ROS can efficiently kill tumor cells. Moreover, the tumor metastasis was also inhibited, providing a different way to treat triple-negative breast cancer, which was easily metastatic and lacked effective treatments in the clinic.

As an alternative to photodynamic therapy (PDT), ultrasound-triggered tumor sonodynamic therapy (SDT) has garnered significant attention, owing to its high tissue penetration, few side effects, and reliable patient compliance. A sonosensitizer is the most important component in SDT, and high-quantum-yield safe sonosensitizers are crucial for SDT. Existing sonosensitizers mainly include organic sonosensitizers and inorganic sonosensitizers. Organic sonosensitizers, mainly some small dye molecules, have been widely studied. However, organic sonosensitizers have limited utility owing to their poor stability, rapid blood clearance, and potential phototoxicity. In contrast, inorganic sonosensitizers have stable chemical properties, long circulation time in the blood and can effectively reduce phototoxicity. In addition to their utilization as sonosensitizers, some inorganic nanoparticles can also operate as carriers for delivering organic sonosensitizers, effectively overcoming the inherent shortcomings of organic small-molecule sonosensitizers. This review mainly focuses on inorganic nanomaterial-based SDT, the possible mechanisms of SDT, and newly developed inorganic sonosensitizers, as well as the challenges and possible solutions associated with their clinical translation are introduced.

Alkaline phosphatase (ALP) as a necessary hydrolase in phosphate metabolism is closely related to various diseases. Ultrasensitive detection of ALP with a convenient and sensitive method is of fundamental importance. In this work, a fluorescence resonance energy transfer (FRET)-based single-particle enumeration (SPE) method is proposed for the quantitative analysis of ALP. This strategy is based on the effective fluorescence suppression by a polydopamine (PDA) shell on the surface of semiconducting polymer nanoparticles (SPNs). PDA with broadband absorption in the UV-vis region can serve as an excellent quencher for SPNs. However, ascorbic acid (AA), the product of the hydrolysis of 2-phosphate-l-ascorbic acid trisodium salt (AAP) in the presence of ALP, can effectively inhibit the self-polymerization of dopamine (DA) to form a PDA layer. Therefore, ALP can be accurately quantified by counting the concentration-related fluorescent particles in the fluorescence image. A linear range from 0.031 to 12.4 μU mL-1 and a limit-of-detection (LOD) of 0.01 μU mL-1 for ALP determination are achieved. The spiked recoveries for ALP determination in a human serum sample are between 90% and 108% with RSD less than 3.1%. In summary, this convenient and sensitive approach proposed here provides promising prospects for ALP detection in a complex biological matrix.

Thermosensitive liposomes have demonstrated great potential for tumor-specific chemotherapy. Near infrared (NIR) dyes loaded liposomes have also shown improved photothermal effect in cancer theranostics. However, the instability of liposomes often causes premature release of drugs or dyes, impeding their antitumor efficacy. Herein, we fabricated a highly stable thermo-responsive bubble-generating liposomal nanohybrid cerasome with a silicate framework, combined with a NIR dye to achieve NIR light stimulated, tumor-specific, chemo-photothermal synergistic therapy. Methods: In this system, NIR dye of 1,1'-Dioctadecyl-3,3,3',3'- Tetramethylindotricarbocyanine iodide (DiR) with long carbon chains was self-assembled with a cerasome-forming lipid (CFL) to encapsulate ammonium bicarbonate (ABC), which was further used for actively loading doxorubicin (DOX), affording a thermosensitive and photosensitive DOX-DiR@cerasome (ABC). Results: The resulting cerasome could disperse well in different media. Upon NIR light mediated thermal effect, ABC was decomposed to generate CO 2 bubbles, resulting in a permeable channel in the cerasome bilayer that significantly enhanced DOX release. After intravenous injection into tumor-bearing mice, DOX-DiR@cerasome (ABC) could be efficiently accumulated at the tumor tissue, as monitored by DiR fluorescence, lasting for more than 5 days. NIR light irradiation was then performed at 36h to locally heat the tumors, resulting in immediate CO 2 bubble generation, which could be clearly detected by ultrasound imaging, facilitating the monitoring process of controlled release of the drug. Significant antitumor efficacy could be obtained for the DOX-DiR@cerasome (ABC) + laser group, which was further confirmed by tumor tissue histological analysis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Multidrug resistance remains one of the main obstacles to efficient chemotherapy of colorectal cancer. Herein, an efficient combination therapeutic strategy is proposed based on porphyrin/camptothecin-floxuridine triad microbubbles (PCF-MBs) with high drug loading contents, which own highly stable co-delivery drug combinations and no premature release. The triad PCF-MBs can act not only as a contrast agent for ultrasound (US)/fluorescence bimodal imaging but also a multimodal therapeutic agent for synergistic chemo-photodynamic combination therapy. Upon local ultrasound exposure under the guidance of ultrasound imaging, in situ conversion of PCF-MBs into porphyrin/camptothecin-floxuridine nanoparticles (PCF-NPs) leads to high accumulation of chemo-drugs and photosensitizer in tumors due to the induced high permeability of the capillary wall and cell membrane temporarily via sonoporation effect, greatly reducing the risk of systemic exposure. Most importantly, it was found that the PCF-MB-mediated photodynamic therapy could significantly reduce the expression of adenosine-triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG 2 ), which is responsible for the drug resistance in chemotherapy, resulting in a prominent intracellular camptothecin increase. In vivo experiments revealed that the PCF-MBs in combination with ultrasound and laser irradiation could achieve a 90% tumor inhibition rate of HT-29 cancer with no recurrence. Therefore, such triad PCF-MB-based combination therapeutic strategy shows great promise for overcoming drug resistance of colorectal cancer and other cancers.

Photoacoustic tomography (PAT) has emerged as a hybrid, nonionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. Here, we demonstrate the application of a novel organic PAT contrast agent based on polypyrrole nanoparticles (PPy NPs). Monodisperse PPy NPs are ∼46 nm in diameter with strong absorption in the near-infrared (NIR) range, which allowed visualization of PPy NP-containing agar gel embedded in chicken breast muscle at a depth of ∼4.3 cm. Compared with PAT images based on the intrinsic optical contrast in mice, the PAT images acquired within 1 h after intravenous administration of PPy NPs showed the brain vasculature with greater clarity than hemoglobin in blood. Preliminary results showed no acute toxicity to the vital organs (heart, liver, spleen, lungs and kidneys) in mice following a single imaging dose of PPy NPs. Our results indicate that PPy NPs are promising contrast agents for PAT with good biocompatibility, high spatial resolution and enhanced sensitivity.

Novel "soft" microbubbles have been fabricated to show outstanding ultrasound imaging capability, and triggered CuS nanoparticles delivery through ultrasound-targeted microbubble destruction for efficient photothermal ablation of cancer cells.

The development of efficient contrast agents for tumor-targeted imaging remains a critical challenge in the clinic. Herein, we proposed a tumor-derived extracellular vesicle (EV)-mediated targeting approach to improve in vivo tumor imaging using ternary downconversion nanoparticles (DCNPs) with strong near infrared II (NIR-II) luminescence at 1,525 nm. The EVs were metabolically engineered with azide group, followed by in vivo labeling of DCNPs through copper-free click chemistry. By taking advantage of the homologous targeting property of tumor derived EVs, remarkable improvement in the tumor accumulation (6.5% injection dose (ID)/g) was achieved in the subcutaneous colorectal cancer model when compared to that of individual DCNPs via passive targeting (1.1% ID/g). Importantly, such bioorthogonal labeling significantly increased NIR-II luminescence signals and prolonged the retention at tumor sites. Our work demonstrates the great potential of EVs-mediated bioorthogonal approach for in vivo labeling of NIR-II optical probes, which provides a robust tool for tumor-specific imaging and targeted therapy. [ABSTRACT FROM AUTHOR]

The development of non-precious and high-efficient electrocatalysts to enhance the activity and stability in alkaline media is impending for massive hydrogen and oxygen production. In this study, NiS 2 nanoparticles array with ellipse-like topography was fabricated via simple hydrothermal and sulfurization treatment. The NiS 2 -400 featured with the unique loose stacking topographic architecture contributes to more exposed active sites, the smaller contact resistance between electrode/electrolyte, faster ion diffusion and electron transfer. As a result, NiS 2 -400 electrode requires only overpotentials of 116 and 178 mV to drive current densities of 10 and 50 mA cm−2 in 1.0 M KOH towards the hydrogen evolution reaction (HER), coupled with a Tafel slope of 93.0 mV dec−1. Moreover, the resultant NiS 2 -400 nanoparticles exhibit excellent electrochemical stability for more than 50 h. In addition, the density functional theory (DFT) calculation further confirms that the (200) facet acts as the predominant active site, contributing to the enhanced HER performance. • MOF-derived NiS 2 was fabricated via hydrothermal and sulfurization treatment. • The obtained NiS 2 -400 possesses a unique loose stacking topography. • Ellipse-like NiS 2 -400 exhibits excellent HER performance. • The (200) facet of NiS 2 catalyst acts as the predominant active sites. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs)-based diagnosis and phototherapy are emerging as the cutting-edge technologies for detection and treatment of cancer but their applications are still limited since insufficient and heterogeneous NPs accumulation in cancer often causes recurrence. To overcome these limitations, multifunctional microbubbles (MBs) were constructed with 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindotricarbocyanine iodide (DiR) and porphyrin grafted lipid (PGL). Both DiR and PGL self-assembled as microbubbles, the as-designed PGL-DiR MBs possess remarkably high drug loading contents (5.8% PGL and 10.38% DiR) and stable co-delivery drug combinations. In vivo experiments showed PGL-DiR MBs could serve as an excellent ultrasound contrast agent to enhance ultrasound imaging greatly for identifying the location and size of the tumors. Upon exposure to ultrasound, in situ conversion of PGL-DiR MBs into nanoparticles resulted in a remarkable increase in fluorescence intensity (~5 folds) in tumor compared with PGL-DiR NPs, validating the enhanced tumor accumulation and cellular uptake of therapeutic agents. PGL-DiR MBs showed complete tumor ablation without recurrence in vivo, while PGL-DiR NPs showed only 72.6% tumor growth inhibition at the same dose. We believe that PGL-DiR MBs will soon reach their full potential as an important class of phototherapeutic formulations and will contribute to remarkable advances in cancer treatments. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The purpose of this study was to test whether dual functional gold nano-shelled microcapsules (GNS-MCs) can be used as an ultrasound imaging enhancer and as an optical absorber for photothermal therapy (PTT) in a rodent model of breast cancer. Methods: GNS-MCs were fabricated with an inner air and outer gold nanoshell spherical structure. Photothermal cytotoxicity of GNS-MCs was tested with BT474 cancer cells in vitro and non-obese diabetes-SCID (NOD/SCID) mice with breast cancer. GNS-MCs were injected into the tumor under ultrasound guidance and treated with near-infrared (NIR) laser irradiation. The photothermal ablative effectiveness of GNS-MCs was evaluated by measuring the surface and internal temperature of the tumor as well as the size of the tumor using histological confirmation. Results: NIR laser irradiation resulted in significant tumor cell death in GNS-MCs-treated BT474 cells in vitro. GNS-MCs were able to serve as an ultrasound enhancer to guide the intratumoral injection of GNS-MCs and ensure their uniform distribution. In vivo studies revealed that NIR laser irradiation increased the intratumoral temperature to nearly 70°C for 8min in GNS-MCs-treated mice. Tumor volumes decreased gradually and tumors were completely ablated in 6 out of 7 mice treated with GNS-MCs and laser irradiation by 17 days after treatment. Conclusion: This study demonstrates that ultrasound-guided PTT with theranostic GNS-MCs is a promising technique for in situ treatment of breast cancer. [Copyright &y& Elsevier]

In this work, MFe2O4 (M = Zn, Cu) nanoparticles were successfully prepared by a hydrothermal method. The structure, morphology, microstructure, specific surface area and electrochemical properties of the resultant particles were characterised by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, nitrogen physical adsorption, charge-discharge test and cyclic voltammetry (CV) method, respectively. The resulting ZnFe2O4 and CuFe2O4 products were sphere-like and cubic-shaped particles and their average size was about 30-40 nm and 60-70 nm, respectively. The initial discharge capacities of ZnFe2O4 and CuFe2O4 electrodes reached 1287.5 mAh g-1 and 1412.3 mAh g-1, respectively, at a current density of 0.2 mA cm-2 in a potential range of 0.0-3.0 V. This indicated that Cu is a better counter ion than Zn. The resulting MFe2O4 nanoparticles are expected to be a promising candidate of anode materials for Li ion batteries. The reaction mechanism of MFe2O4 nanoparticles in Li ion batteries was also discussed based on the CV of Li/MFe2O4 cell. [ABSTRACT FROM AUTHOR]

We report the novel synthesis of luminescent carbon nanoparticles (CNPs) and their applications as yellow emission conversion phosphors. CNPs were obtained in a hydrothermal process using hexamethylenetetramine (HMT)/glucose mixed solution as precursor. The mixed glucose is found to facilitate the decomposition of HMT, which leads to rapid and low-temperature growth of CNPs. CNPs (quantum yield exceeding 58%) solutions exhibit strong blue-green emission with ultraviolet light illumination and possess typical excitation-dependent photoluminescence (PL) behavior. CNPs were also coated onto ultraviolet and blue LEDs. Broad yellow emission was both achieved with ultraviolet or blue light excitation, indicating such CNPs phosphors can be used in fluorescent lamps or white LEDs. The nontoxic nature and broad yellow emission indicates potential applications of CNPs for phosphor-based white light-emitting devices. [ABSTRACT FROM AUTHOR]

Abstract: In this work, graphite encapsulated Fe nanoparticles and thin carbon nanotubes (CNTs) supported on the pristine CNTs, respectively, were synthesized using plasma enhanced chemical vapor deposition via efficiently controlling the flow rate of discharging CH4 and H2 gas. The properties of the obtained hybrid materials were characterized with superconducting quantum interference and field emission measurements. The results showed that the encapsulated Fe nanoparticles had diameters ranging from 1 to 30nm, and this hybrid nanocomposite exhibited a ferromagnetic behavior at room temperature. Thin CNTs with an average diameter of 6nm were attached to the surface of the prepared CNTs, which exhibited a lower turn-on field and higher emission current density than the pristine CNTs. The Fe nanoparticles either encapsulated with graphite or used as catalyst for thin CNTs growth were all originated from the pyrolysis of ferrocene. [Copyright &y& Elsevier]