Efficient Ablation Research Articles

Efficient Ablation, further GHz Burst Polishing, and Surface Texturing by Ultrafast Laser

Efficient Ablation, further GHz Burst Polishing, and Surface Texturing by Ultrafast Laser

Utilizing Carbon Nanomaterials for Enhanced Photothermal Therapy in Breast Cancer Treatment

Breast cancer is the most often diagnosed cancer in women and the second largest cause of cancer mortality worldwide. Photothermal therapy (PTT) has emerged as a viable cancer treatment that uses near-infrared (NIR) light-absorbing chemicals to selectively heat and destroy tumor cells while sparing healthy tissue. PTT has advantages such as high specificity, little invasiveness, and efficient tumor ablation. Recent advances include developing imageable photothermal agents to aid in therapy planning. This review focuses on the function of carbon nanoparticles in PTT, investigating their processes and advantages and analysing in vitro and in vivo investigations. Carbon nanomaterials like carbon nanotubes (CNTs) and graphene have a large surface area, great electrical conductivity, and biocompatibility, making them ideal for PTT. Carbon nanomaterials absorb NIR light, enabling deep tissue penetration and targeted heating of tumor tissues, resulting in necrosis and apoptosis. Carbon nanomaterials also increase tumor vascular permeability, which promotes chemotherapeutic drug accumulation and improves treatment results. Repurposing carbon nanomaterials for increased PTT is a potential method because of its capacity to target various pathways, select cytotoxicity against cancer cells, and synergistic effects with other anticancer drugs.

Simulation and experimental study of femtosecond laser ablation mechanisms of NiCoCrAlY coatings

To enhance the adhesion of turbine blade thermal barrier coating systems using the LST method, a thorough understanding of the ablation mechanism of NiCoCrAlY bond coat material by femtosecond laser systems is essential for producing high-quality textured grooves. This study systematically investigates the ablation mechanisms of NiCoCrAlY material, exploring the effects of laser energy density, laser scanning speed, and the number of laser scans on the ablation of NiCoCrAlY. Numerical simulations based on the two-temperature model were conducted, providing a comprehensive analysis of thermal effects, heat accumulation, and material response during the laser ablation process. The experimental results indicate that 1) the ablation phenomenon caused by heat accumulation becomes evident as the laser energy density increases from 1.948 J/cm2 to 4.521 J/cm2, with the accumulated heat reaching 1525.2 K, leading to distinct melting residues and heat-affected zones on the groove walls. 2) The change in laser scanning speed also affects heat accumulation. Using a laser scanning speed of 800 mm/s results in a high material removal rate, smooth machined walls, and a uniform surface with no significant heat-affected zones. 3) Excessively high numbers of laser scans shift the laser focus to the bottom of the groove. The high concentration of laser energy causes intense localized ablation, forming sharp bases with numerous cracks and melting residues. To achieve efficient and high-quality laser ablation, it is necessary to ensure that the number of scans remains below 40.

Transgenic zebrafish as a model for investigating diabetic peripheral neuropathy: investigation of the role of insulin signaling.

Diabetic peripheral neuropathy (DPN), a complication of diabetes mellitus (DM), is a neurodegenerative disorder that results from hyperglycemic damage and deficient insulin receptor (IR) signaling in peripheral nerves, triggered by failure of insulin production and insulin resistance. IR signaling plays an important role in nutrient metabolism and synaptic formation and maintenance in peripheral neurons. Although several animal models of DPN have been developed to identify new drug candidates using cytotoxic reagents, nutrient-rich diets, and genetic manipulations, a model showing beneficial effects remains to be established. In this study, we aimed to develop a DPN animal model using zebrafish to validate the effects of drug candidates on sensory neuropathy through in vivo imaging during the early larval stage. To achieve this, we generated Tg (ins:gal4p16);Tg (5uas:epNTR-p2a-mcherry) zebrafish using an enhanced potency nitroreductase (epNTR)-mediated chemogenetic ablation system, which showed highly efficient ablation of pancreatic β-cells following treatment with low-dose metronidazole (MTZ). Using in vivo live imaging, we observed that sensory nerve endings and postsynaptic formation in the peripheral lateral line (PLL) were defective, followed by a disturbance in rheotaxis behavior without any locomotory behavioral changes. Despite defects in sensory nerves and elevated glucose levels, both reactive oxygen species (ROS) levels, a primary cause of DPN, and the number of ganglion cells, remained normal. Furthermore, we found that the activity of mTOR, a downstream target of IR signaling, was decreased in the PLL ganglion cells of the transgenic zebrafish. Our data indicates that peripheral neuropathy results from the loss of IR signaling due to insulin deficiency rather than hyperglycemia alone.

Energy-Efficient and Effective MCF-7 Cell Ablation and Electrothermal Therapy Enabled by M13-WS2-PEG Nanostructures.

Thermal agents (TAs) have exhibited promise in clinical tests when utilized in cancer thermal therapy (TT). While rapid degradation of TAs may address safety concerns, it limits the thermal stability required for effective treatment. TAs, which possess exceptional thermal stability, experience gradual deterioration. There are few approaches that effectively address the trade-off between improving thermal stability and simultaneously boosting material deterioration. Here, we control the thermal character of tungsten disulfide (WS2)-based 2D materials by utilizing an M13 phage through Joule heating (the M13-WS2-PEG nanostructures were generated and termed a tripartite (T) nanostructure), and developed a T nanostructure-driven TT platform (we called it T-TT) for efficient thermal ablation of clinically relevant MCF-7 cells. A relative cell viability of ~59% was achieved, as well as onset time of degradation of ~0.5 week. The T-TT platform also discloses an energy density of 5.9 J/mL. Furthermore, the phage-conjugated WS2 can be utilized to achieve ultrasound imaging for disease monitoring. Therefore, this research not only presents a thermal agent that overcomes TA limitations, but also demonstrates a practical application of WS2-type material system in ultra-energy efficient and effective cancer therapy.

A Closed-Loop Nanosystem Based on Piezoelectric Sensor and Pd-Nanoshell Photothermal Ablation for Renal Denervation to Treat Hypertension.

Renal sympathetic nerves play a crucial role in the pathogenesis of hypertension, and renal denervation (RDN) is a new solution for patients with refractory hypertension. However, current RDN techniques show inconsistent results in clinical application probably owing to incomplete endovascular ablation of the sympathetic nerves and a lack of measures to localize and assess efficacy. In this study, a closed-loop RDN system consisting of a sensing unit with a piezoelectric thin-film sensor (PTFS) and a treatment unit with a hollow Pd nanoparticle shell (PdNPS) with a diameter of 202.0nm for photothermal neural ablation is constructed. The PTFS can monitor and collect arterial pulsation and blood pressure (BP) and direct PdNPS to maximize RDN. PdNPS maintains a local temperature of 58-62°C under near-infrared-II irradiation (1,064nm) to achieve effective RDN within a range of 90-120s treatment window. Photothermal ablation significantly inhibits the activities of renal sympathetic nerves post-procedure and after one month and reduces the elevation of BP by > 50%. The novel closed-loop system enables safe and efficient targeting, dynamic monitoring, and ablation of the renal sympathetic nerves. This closed-loop system provides a new strategy for RDN technology and even for treating sympathetic nerve-related chronic diseases.

Biodegradable oxygen-evolving metalloantibiotics for spatiotemporal sono-metalloimmunotherapy against orthopaedic biofilm infections

Pathogen-host competition for manganese and intricate immunostimulatory pathways severely attenuates the efficacy of antibacterial immunotherapy against biofilm infections associated with orthopaedic implants. Herein, we introduce a spatiotemporal sono-metalloimmunotherapy (SMIT) strategy aimed at efficient biofilm ablation by custom design of ingenious biomimetic metal-organic framework (PCN-224)-coated MnO2-hydrangea nanoparticles (MnPM) as a metalloantibiotic. Upon reaching the acidic H2O2-enriched biofilm microenvironment, MnPM can convert abundant H2O2 into oxygen, which is conducive to significantly enhancing the efficacy of ultrasound (US)-triggered sonodynamic therapy (SDT), thereby exposing bacteria-associated antigens (BAAs). Moreover, MnPM disrupts bacterial homeostasis, further killing more bacteria. Then, the Mn ions released from the degraded MnO2 can recharge immune cells to enhance the cGAS-STING signaling pathway sensing of BAAs, further boosting the immune response and suppressing biofilm growth via biofilm-specific T cell responses. Following US withdrawal, the sustained oxygenation promotes the survival and migration of fibroblasts, stimulates the expression of angiogenic growth factors and angiogenesis, and neutralizes excessive inflammation. Our findings highlight that MnPM may act as an immune costimulatory metalloantibiotic to regulate the cGAS-STING signaling pathway, presenting a promising alternative to antibiotics for orthopaedic biofilm infection treatment and pro-tissue repair.

Aggregation-Induced Emission-Active Organic Nanoagent with High Photothermal Conversion Efficiency for Near-Infrared Imaging-Guided Tumor Photothermal Therapy.

Photothermal therapy (PTT) provides a great prospect for noninvasive cancer therapy. However, it is still highly challenging to construct photothermal agents (PTAs) with the desired performances for imaging-guided PTT applications. Herein, a D-A-D-type naphthalene diamine (NDI)-based photothermal nano-PTAs NDS-BPN NP with near-infrared region (NIR) emission at 822 nm, aggregation-induced emission (AIE), high photothermal conversion efficiency (55.05%), and excellent photothermal stability is successfully designed and prepared through a simple two-step engineering method by using a new AIE molecule NDS-BPN and DSPE-PEG2000 as precursors. The prepared PTT nanoagents NDS-BPN NPs have been further applied for efficient photothermal ablation of cancer cells in vitro and also achieved the NIR fluorescent image-guided PTT tumor therapy in vivo with satisfactory results. We believe that this work provides an attractive NIR AIE NDI-based nano-PTA for the phototherapy of tumors as well as develops the construction strategy of NDI molecular-based photothermal nanoagents with desired performances for imaging-guided PTT.

Abstract 47: Deletion of PRR in AgRP Neurons of the Arcuate Nucleus Contributes to the Development of DOCA-Salt Hypertension

Agouti-related protein (AgRP) neurons, a key neuronal population within the arcuate nucleus (ARC), are known for their pivotal roles in regulating energy- and glucose homeostasis. However, their involvement in cardiovascular regulation remains poorly understood. Using RNAscope in situ hybridization, we found that 95.4% of the ARC AgRP neurons express the (pro)renin receptor (PRR), a component of the brain renin-angiotensin system that is crucial for blood pressure (BP) regulation. We therefore hypothesized that PRR signaling in the ARC AgRP neurons plays a regulatory role in the development of hypertension. To test this hypothesis, we selectively deleted PRR in ARC AgRP neurons by crossing AgRP-IRES-Cre mice with PRR fl/fl mice. Using RNAscope, as expected, AgRP Cre+ PRR fl/y mice displayed a significantly lower PRR mRNA in the ARC AgRP neurons than WT mice (76.3 ± 6.1 vs. 127.7 ± 2.9 AFU, p < 0.05), indicating efficient ablation of PRR in ARC AgRP neurons. To examine the impact of PRR deletion in the ARC AgRP neurons on BP, the AgRP Cre+ PRR fl/y and control mice were implanted with telemetry probes to monitor BP continuously. After baseline recording, mice received DOCA-salt treatment (50 mg DOCA + saline as drinking water) for two weeks. BP variability and standard time domain heart rate variability (HRV) parameters, including overall HRV (SDNN) and short-term HRV (rMSSD), were analyzed from beat-to-beat intervals (n = 2-7 mice/group). At baseline, there was no difference between the two groups in BP, BP variability, and HRV. Two weeks of DOCA-salt induced a significantly higher BP in AgRP Cre+ PRR fl/y mice than the controls (156.2 ± 6 vs. 119.4 ± 3 mmHg, p < 0.05), while BP variability did not differ between the two groups. Noteworthy, AgRP Cre+ PRR fl/y mice exhibited lower SDNN than the controls (13.3 ± 4 vs. 19.4 ± 4 ms), indicating increased sympathetic and/or reduced parasympathetic nervous activity. This lower SDNN suggests impaired cardiac autonomic function and adaptability to physiological demands in AgRP Cre+ PRR fl/y mice. Concurrently, AgRP Cre+ PRR fl/y mice showed a lower rMSSD (4.7 ± 0.5 vs. 10.8 ± 3.5 ms), implying reduced parasympathetic activity. In conclusion, deletion of PRR in the ARC AgRP neurons results in compromised cardiac autonomic function associated with the development of hypertension. Our findings underscore a novel protective role of PRR signaling in the ARC AgRP neurons in BP regulation.

Photothermal Catalytic Reduction and Bone Tissue Engineering Towards a Three-in-One Therapy Strategy for Osteosarcoma.

Osteosarcoma is one of the most dreadful bone neoplasms in young people, necessitating the development of innovative therapies that can effectively eliminate tumors while minimizing damage to limb function. An ideal therapeutic strategy should possess three essential capabilities: antitumor effects, tissue-protective properties, and the ability to enhance osteogenesis. In this study, self-assembled Ce-substituted molybdenum blue (CMB) nanowheel crystals are synthesized and loaded onto 3D-printed bioactive glass (CMB@BG) scaffolds to develop a unique three-in-one treatment approach for osteosarcoma. The CMB@BG scaffolds exhibit outstanding photothermally derived tumor ablation within the near-infrared-II window due to the surface plasmon resonance properties of the CMB nanowheel crystals. Furthermore, the photothermally synergistic catalytic effect of CMB promotes the rapid scavenging of reactive oxygen species caused by excessive heat, thereby suppressing inflammation and protecting surrounding tissues. The CMB@BG scaffolds possess pro-proliferation and pro-differentiation capabilities that efficiently accelerate bone regeneration within bone defects. Altogether, the CMB@BG scaffolds that combine highly efficient tumor ablation, tissue protection based on anti-inflammatory mechanisms, and enhanced osteogenic ability are likely to be a point-to-point solution for the comprehensive therapeutic needs of osteosarcoma.

Novel ambient-condition solid-state synthesis route of nanocrystalline TiN thin films via spark plasma ablation deposition

By utilizing a novel, green and efficient spark plasma ablation deposition, <10 nm size titanium nitride nanoparticles were obtained. The prepared nanopowder material can be utilized for the deposition of a nanocrystalline thin film. The solid-state synthesis was performed completely at ambient conditions, without the use of solvents and post-processing. Transmission electron microscopy confirmed the size of the nanoparticles within the range of less than 10 nm with primary particles as small as 3 nm, while selective area diffraction confirmed fits cubic titanium nitride (TiN) crystal structure. The geometry (thickness and surface roughness) of the deposited thin films could be varied depending on the sparking current and flow rate. Raman spectroscopy suggested the specific morphology that stems from the plastic deformation of nanoparticles upon collision with the substrate might influence the nanolocal structural environment due to a high surface contribution of tensile stress.

A novel guided approach to radiofrequency ablation of thyroid nodules: the Toronto Sunnybrook experience.

Thyroid nodules are extremely common being detected by ultrasonography in up to 67% of the population, with current surgical tenet maintaining that lobectomy is required for large symptomatic benign nodules or autonomously functionally nodules resulting in a risk of hypothyroidism or recurrent laryngeal nerve injury even in high volume centres. The introduction of radiofrequency ablation (RFA) has allowed thermal ablation of both benign and autonomously functioning thyroid nodules with minimal morbidity. The moving shot technique is the most well-established technique in performing RFA of thyroid nodules, and has proven to be safe, efficacious, accurate and successful amongst experienced clinicians. The purpose of this article to propose the use of a novel guide when performing RFA of thyroid nodules in clinical practice utilizing the moving shot technique. The technique proposed of RFA involves the use of a 10MHz linear ultrasound probe attached to an 18G guide which provides robust in line visualisation of a 7cm or 10cm radiofrequency probe tip (STARmed, Seoul, Korea) utilizing the trans isthmic moving shot technique. A geometric analysis of the guide has been illustrated diagrammatically. The use of an 18G radiofrequency probe guide (CIVCO Infiniti Plus™ Needle Guide) maintains in line visualisation of the radiofrequency probe over a cross-sectional area up to 28cm2, facilitating efficient and complete ablation of conceptual subunits during RFA of thyroid nodules. Radiofrequency ablation of thyroid nodules can be performed safely and effectively using the novel radiofrequency probe guide proposed which we believe potentially improves both accuracy and overall efficiency, along with operator confidence in maintaining visualisation of the probe tip, and hence we believe provides a valuable addition to the armamentarium of clinicians wishing to embark on performing RFA of thyroid nodules.

Mesoporous platinum@copper selenide-based NIR-II photothermal agents with photothermal conversion efficiency over 80% for photoacoustic imaging and targeted cancer therapy

Elevating photothermal conversion efficiency (PCE) is the key to enhance curative efficacy during photothermal therapy. Nevertheless, current functionalized or synthetic methods for preparing photothermal agents with high PCE are too complicated, greatly hindering the development of photothermal therapy. In this study, we developed a tumor-targeting flower-like nanocomposite termed mesoporous platinum nanoparticles@Cu2-xSe-AS1411 (MPNPs@Cu2-xSe-AS1411, denoted as MPCSA) with remarkable PCE for high-resolution photoacoustic (PA) imaging guided photothermal/chemodynamic therapy for tumor ablation. We discovered that MPNPs served as carriers for delivering PA contrast agents. Cu2-xSe nanosheets emerged as promising near-infrared-II (NIR-II) PA imaging and photothermal/chemodynamic therapy agents owing to their strong localized surface plasmon resonance property in the NIR-II region. The amine-modified AS1411 aptamer, which is connected to the surface of the flower-like MPNPs@Cu2-xSe can target the nucleolar protein on the surface of 4T1 cells, achieving the accumulation of MPCSA at the tumor site in mice. Notably, these MPCSA nano-flowers exhibited an excellent PCE up to 82.33 % under 1064 nm laser irradiation, resulting in highly efficient cancer cell ablation and greatly hindering in vivo tumor growth. This study has paved the way for imaging-guided accurate cancer diagnosis and targeted cancer therapy.

Injectable Therapeutic Hydrogel with H2O2 Self-Supplying and GSH Consumption for Synergistic Chemodynamic/Low-Temperature Photothermal Inhibition of Postoperative Tumor Recurrence and Wound Infection.

Postoperative tumor recurrence and wound infection remain significant clinical challenges in surgery, often requiring adjuvant therapies. The combination treatment of photothermal therapy (PTT) and chemodynamic therapy (CDT) has proven to be effective in cancer treatment and wound infection. However, the hyperthermia during PTT increases the risk of normal tissue damage, severely impeding its application. Moreover, the efficacy of CDT is limited by insufficient hydrogen peroxide (H2O2) and excessive glutathione (GSH) levels at tumor or infection sites. Herein, an injectable and multifunctional CuO2@Au hydrogel system (CuO2@Au Gel) is developed for synergistic CDT and low-temperature PTT (LTPTT) to prevent tumor recurrence and bacterial wound infections. CuO2@Au Gel is constructed by embedding therapeutic CuO2@Au into low-melting point agarose hydrogel. In vitro and in vivo experiments confirm that the CuO2@Au in CuO2@Au Gel is capable of self-supplying H2O2 and depleting GSH, exhibiting effective CDT effect in acidic tumor or bacterial infected microenvironment. Additionally, it exhibits favorable photothermal conversion ability, inducing localized temperature elevation and synergistically enhancing CDT efficiency. The prepared CuO2@Au Gel demonstrates efficient tumor ablation capability in post-surgery recurrence mouse models and exhibits promising anti-infective efficiency in bacterial infection wound models, indicating significant potential in adjuvant therapy for post-surgical treatment and recovery.

Nanoengineered 3D-printing scaffolds prepared by metal-coordination self-assembly for hyperthermia-catalytic osteosarcoma therapy and bone regeneration

The integration of functional nanomaterials with tissue engineering scaffolds has emerged as a promising solution for simultaneously treating malignant bone tumors and repairing resected bone defects. However, achieving a uniform bioactive interface on 3D-printing polymer scaffolds with minimized microstructural heterogeneity remains a challenge. In this study, we report a facile metal-coordination self-assembly strategy for the surface engineering of 3D-printed polycaprolactone (PCL) scaffolds with nanostructured two-dimensional conjugated metal–organic frameworks (cMOFs) consisting of Cu ions and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP). A tunable thickness of Cu-HHTP cMOF on PCL scaffolds was achieved via the alternative deposition of metal ions and HHTP. The resulting composite PCL@Cu-HHTP scaffolds not only demonstrated potent photothermal conversion capability for efficient OS ablation but also promoted the bone repair process by virtue of their cell-friendly hydrophilic interfaces. Therefore, the cMOF-engineered dual-functional 3D-printing scaffolds show promising potential for treating bone tumors by offering sequential anti-tumor effects and bone regeneration capabilities. This work also presents a new avenue for the interface engineering of bioactive scaffolds to meet multifaceted demands in osteosarcoma-related bone defects.

Efficient Ablation, further GHz Burst Polishing, and Surface Texturing by Ultrafast Laser

A large variety of ultrafast laser‐matter interaction regimes and different processed surface finishing qualities of stainless steel can be achieved by varying the laser processing parameters. The optimization of the laser fluence to the most efficient ablation also leads to the lowest surface roughness of the ablated material. High laser fluence together with a high pulse repetition rate leads to heat accumulation, which results in the formation of microstructures with various morphology and scales. The use of GHz bursts allows a rough stainless‐steel surface to be smoothed and even polished. In this work, the fast and high‐quality milling of 2.5D cavities is demonstrated. Laser beam spot optimization is used to increase the throughput of the high‐power femtosecond laser (67.8 W), resulting in an ablation rate of 13 mm3 min−1. The complex cavities are produced by laser milling and cutting in layers. The formation of surface structures on stainless steel because of laser irradiation has been demonstrated. The possibilities of further GHz burst polishing are examined on previously laser‐milled stainless steel using with lowest possible surface roughness. The ability to polish the surface with microstructures below the original roughness is demonstrated by bursts of ultrashort pulses with a repetition rate in the GHz range. It has been demonstrated that mold milling in stainless steel designed for LED diffusers can be fabricated using a modern femtosecond laser source together with beam size optimization technique for efficient ablation with low surface roughness, layer‐by‐layer milling techniques, and GHz burst polishing techniques.

Optical probing of ultrafast laser-induced solid-to-overdense-plasma transitions

Understanding the solid target dynamics resulting from the interaction with an ultrashort laser pulse is a challenging fundamental multi-physics problem involving atomic and solid-state physics, plasma physics, and laser physics. Knowledge of the initial interplay of the underlying processes is essential to many applications ranging from low-power laser regimes like laser-induced ablation to high-power laser regimes like laser-driven ion acceleration. Accessing the properties of the so-called pre-plasma formed as the laser pulse’s rising edge ionizes the target is complicated from the theoretical and experimental point of view, and many aspects of this laser-induced transition from solid to overdense plasma over picosecond timescales are still open questions. On the one hand, laser-driven ion acceleration requires precise control of the pre-plasma because the efficiency of the acceleration process crucially depends on the target properties at the arrival of the relativistic intensity peak of the pulse. On the other hand, efficient laser ablation requires, for example, preventing the so-called “plasma shielding”. By capturing the dynamics of the initial stage of the interaction, we report on a detailed visualization of the pre-plasma formation and evolution. Nanometer-thin diamond-like carbon foils are shown to transition from solid to plasma during the laser rising edge with intensities < 1016 W/cm². Single-shot near-infrared probe transmission measurements evidence sub-picosecond dynamics of an expanding plasma with densities above 1023 cm−3 (about 100 times the critical plasma density). The complementarity of a solid-state interaction model and kinetic plasma description provides deep insight into the interplay of initial ionization, collisions, and expansion.

Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.

Dual Enzyme-Encapsulated Materials for Biological Cascade Chemistry and Synergistic Tumor Starvation.

Framework and polymeric nanoreactors (NRs) have distinct advantages in improving chemical reaction efficiency in the tumor microenvironment (TME). Nanoreactor-loaded oxidoreductase enzyme is activated by tumor acidity to produce H2O2 by increasing tumor oxidative stress. High levels of H2O2 induce self-destruction of the vesicles by releasing quinone methide to deplete glutathione and suppress the antioxidant potential of cancer cells. Therefore, the synergistic effect of the enzyme-loaded nanoreactors results in efficient tumor ablation via suppressing cancer-cell metabolism. The main driving force would be to take advantage of the distinct metabolic properties of cancer cells along with the high peroxidase-like activity of metalloenzyme/metalloprotein. A cascade strategy of dual enzymes such as glucose oxidase (GOx) and nitroreductase (NTR) wherein the former acts as an O2-consuming agent such as overexpression of NTR and further amplified NTR-catalyzed release for antitumor therapy. The design of cascade bioreductive hypoxia-responsive drug delivery via GOx regulates NTR upregulation and NTR-responsive nanoparticles. Herein, we discuss tumor hypoxia, reactive oxygen species (ROS) formation, and the effectiveness of these therapies. Nanoclusters in cascaded enzymes along with chemo-radiotherapy with synergistic therapy are illustrated. Finally, we outline the role of the nanoreactor strategy of cascading enzymes along with self-synergistic tumor therapy.

Chymotrypsin etched ultrasmall gold nanoclusters for dual response diagnosis and deeply penetrated chemodynamic therapy of pancreatic cancer

Pancreatic cancer (PC) is a highly invisible malignancy for which the early diagnosis is crucial to achieve the best treatment outcome. Abnormalities in serum chymotrypsin (ChT) are commonly associated with the development of PC, suggesting its potential role as a novel biomarker candidate. Herein, we report a ChT-responsive ultrasmall apo catalase-stabilized gold nanoclusters (AuCATapo NCs, core size ∼2 nm) with remarkable fluorescence and peroxidase (POD)-like activity. It can achieve "fluorescence" and "colorimetric" dual detection of ChT, with a wide detection range (0 – 100 μg/mL) and a low detection limit (0.029 μg/mL). Additionally, the weak acidity (pH 6.2 – 6.8) in the tumor microenvironment can meet the optimal catalytic capacity of deeply penetrated AuCATapo NCs, which generates cytotoxic reactive oxygen species to cause thorough tumor damage effects. The ChT-cleaved AuCATapo NCs may expose more catalytic active sites, resulting in higher tumor cytotoxicity, as demonstrated in both in vitro and in vivo models. Generally, these NCs probes can simultaneously realize accurate detection of ChT and efficient pancreatic tumor ablation via nanozyme based catalytic therapy, opening up a new idea of "diagnosis and treatment integration" for PC.