In Vivo Ultrasound Imaging of Macrophages Using Acoustic Vaporization of Internalized Superheated Nanodroplets.

Activating patients' immune cells, either by reengineering them or treating them with bioactive molecules, has been a breakthrough in the field of immunotherapy and has revolutionized treatment, especially against cancer. As immune cells naturally home to tumors or injured tissues, labeling such cells holds promise for non-invasive tracking and biologic manipulation. Our study demonstrates that macrophages loaded with extremely low boiling point perfluorocarbon nanodroplets not only survive ultrasound-induced phase change but also maintain their phagocytic function. Unlike observations made when using higher boiling point perfluorocarbon nanodroplets, our results show that phase change occurs intracellularly at a low mechanical index using a clinical scanner operating within the energy limit set by the Food and Drug Administration (FDA). After nanodroplet-loaded macrophages were given intravenously to nude rats, they were invisible in the liver when imaged at a very low mechanical index using a clinical ultrasound scanner. They became visible when power was increased but still within the FDA limits up to 8 h after administration. The acoustic labeling and in vivo detection of macrophages using a clinical ultrasound scanner represent a paradigm shift in the field of cell tracking and pave the way for potential therapeutic strategies in the clinical setting.

Copper-cysteamine nanoparticle-mediated microwave dynamic therapy improves cancer treatment with induction of ferroptosis.

Photodynamic Therapy (PDT) holds a great promise for cancer patients, however, due to the hypoxic characteristics of most solid tumors and the limited penetration depth of light in tissues, the extensive clinical application of PDT is limited. Herein, we report microwave induced copper-cysteamine (Cu-Cy) nanoparticles-based PDT as a promising cancer treatment to overcome cancer resistance in combination with ferroptosis. The treatment efficiency of Cu-Cy-mediated microwave dynamic therapy (MWDT) tested on HCT15 colorectal cancer (CRC) cells via cell titer-blue cell viability assay and live/dead assay reveal that Cu-Cy upon MW irradiation can effectively destroy HCT15 CRC cells with average IC-50 values of 20 µg/mL. The cytotoxicity of Cu-Cy to tumor cells after MW stimulation can be alleviated by ferroptosis inhibitor. Furthermore, Cu-Cy mediated MWDT could deplete glutathione peroxide 4 (GPX4) and enhance lipid peroxides (LPO) and malondialdehyde (MDA). Our findings demonstrate that MW-activated Cu-Cy killed CRC cells by inducing ferroptosis. The superior in vivo antitumor efficacy of the Cu-Cy was corroborated by a HCT15 tumor-bearing mice model. Immunohistochemical experiments showed that the GPX4 expression level in Cu-Cy + MW group was significantly lower than that in other groups. Overall, these findings demonstrate that Cu-Cy nanoparticles have a safe and promising clinical application prospect in MWDT for deep-seated tumors and effectively inhibit tumor cell proliferation by inducing ferroptosis, which provides a potential solution for cancer resistance.

FeS2 Loaded Porous SiO2 Ball as a Tweezers Recoverable Heterogeneous Fenton Catalyst with Enhanced Recyclability.

We report a novel FeS2 loaded large SiO2 sphere (diameter of 3 cm) via double immobilization with (3-mercaptopropyl)trimethoxysilane (KH590) as a highly efficient, stable, and tweezers-recoverable heterogeneous Fenton-like catalyst (FeS2/KH590/SiO2@KH590). Notably, as-prepared composite catalyst exhibits a significant recycling improvement (10 runs) over free FeS2 powder (3 runs). The outstanding recyclability and stability of FeS2/KH590/SiO2@KH590 can be attributed to the passivation of FeS2 nanoparticles on SiO2 surface by KH590 and subsequent prevention of Fe2+ leaching. Overall, our work provides a new avenue towards fabricating composite Fenton-like catalyst with high stability, enhanced recyclability and the advantage of easy separation.

Optimization of Eu3+ Luminescence in DMSO as a Multiparameter Method for Trace Water Detection.

Photoluminescence of Eu3+ in DMSO is intense and ultrasensitive to water, thereby providing a novel method for water detection. Herein, for the first time, we investigated the effects of Eu3+ concentration on luminescence and developed a multiparameter method for trace water detection based on a single luminescence agent. To further extend its practical applications, we explored its performance for water detection in ethanol and gasoline. Our findings demonstrate that it is a sensitive and reliable probe for the detection of a wide concentration range of water in ethanol (0-24.24%) and gasoline (0-32.43%), making Eu-DMSO a promising candidate to detect water in a wide concentration range. These phenomena not only make Eu-DMSO a sensitive agent for in situ water detection in real time but also provide scientifically interesting mechanisms behind its application as a water sensing probe.

Copper-Cysteamine Nanoparticles as a Heterogeneous Fenton-Like Catalyst for Highly Selective Cancer Treatment.

Herein, for the first time, we report copper-cysteamine (Cu-Cy) nanoparticles having Cu1+ instead of Cu2+ as an efficient heterogeneous Fenton-like catalyst for highly selective cancer treatment. Initial measurements of Cu-Cy's hydroxyl radical generation ability show that it behaves as a Fenton-like reagent in the presence of H2O2 (100 µM) at pH 7.4, and that its Fenton-like activity is dramatically enhanced under acidic conditions (pH 6.5 and 5.5). Notably, Cu-Cy exhibits high stability and minimal copper release during the Fenton-like reaction, demonstrating its potency as a heterogeneous Fenton-like catalyst with a low cytotoxic effect. Through extensive in vitro studies, Cu-Cy NPs are found to generate a significantly higher level of ROS, thereby causing significantly more destruction to cancerous cells than to normal cells without the need for exogenous additives, such as H2O2. To the best of our knowledge, the average IC-50 value of Cu-Cy to cancer cells (11 µg/mL) is the lowest among reported heterogeneous Fenton-like nanocatalyst so far. Additionally, compared to cancer cells, Cu-Cy NPs display substantially higher IC-50 value toward normal cells (50 µg/mL), suggesting high selectivity. Overall, Cu-Cy NPs can participate in heterogeneous Fenton-like activity with elevated H2O2 under acidic conditions to produce significantly higher levels of hydroxyl radicals in cancer cells when compared to normal cells, resulting in selective cytotoxicity to cancer cells.

Combination of Disulfiram and Copper-Cysteamine Nanoparticles for an Enhanced Antitumor Effect on Esophageal Cancer.

Esophageal cancer (EC) is the sixth leading cause of cancer deaths worldwide with a low 5-year survival rate. More effective chemotherapeutic drugs, either new or repurposing ones, are urgently needed. Disulfiram (DSF) is a safe and public domain drug for alcohol addiction treatment and later shown to have anti-cancer capability, especially when administrated together with copper. The present study is to test the hypothesis that a newly developed copper-cysteamine (Cu-Cy) nanoparticles (NPs) can enhance the anti-tumor effect of DSF on esophageal cancer with reduced risk of copper poisoning. Our results showed that Cu-Cy NPs could greatly facilitate DSF to inhibit cell proliferation in cultured human esophageal cancer cells. Interestingly, the combined inhibitory function could be further enhanced when DSF and Cu-Cy NPs were present at an optimal molar ratio of 1:4. The results of the change in physical color, UV-vis absorption and fluorescence spectra, X-ray diffraction patterns, and FTIR spectra from a mixture of DSF and Cu-Cy NPs suggest a possible reaction between DSF and Cu-Cy NPs and the formation of new materials. Furthermore, cellular mechanistic studies revealed that the combination of DSF and Cu-Cy NPs resulted in reactive oxygen species (ROS) accumulation, and blocked nuclear translocation of NF-ƙB (p65) in esophageal cancer cells. Moreover, in xenograft nude mice, combined administration of DSF and Cu-Cy NPs greatly inhibited tumor growth without noticeable histological toxicity, while any single agent at the same doses presented no inhibitory function. Together, this study demonstrates an effective anti-cancer function of combined treatment of DSF and Cu-Cy NPs in vitro and in vivo, which could be a promising new chemotherapy for esophageal cancer patients.

A powerful combination of copper-cysteamine nanoparticles with potassium iodide for bacterial destruction.

Herein, for the first time, we demonstrate that the combination of copper-cysteamine (Cu-Cy) nanoparticles (NPs) and potassium iodide (KI) can significantly inactivate both Gram-positive MRSA and Gram-negative E. coli. To uncover the mystery of the killing, the interaction of KI with Cu-Cy NPs was investigated systematically and the products from their interaction were identified. No copper ions were released after adding KI to Cu-Cy NPs in cell-free medium and, therefore, it is reasonable to conclude that the Fenton reaction induced by copper ions is not responsible for the bacterial killing. Based on the observations, we propose that the major killing mechanism involves the generation of toxic species, such as hydrogen peroxide, triiodide ions, iodide ions, singlet oxygen, and iodine molecules. Overall, the powerful combination of Cu-Cy NPs and KI has good potential as an independent treatment or a complementary antibiotic treatment to infectious diseases.

Effects of Nanoparticle Size and Radiation Energy on Copper-Cysteamine Nanoparticles for X-ray Induced Photodynamic Therapy.

The Copper-cysteamine (Cu-Cy) nanoparticle is a novel sensitizer with a potential to increase the effectiveness of radiation therapy for cancer treatment. In this work, the effect of nanoparticle size and the energy of X-rays on the effectiveness of radiation therapy are investigated. The effect of the particle size on their performance is very complicated. The nanoparticles with an average size of 300 nm have the most intense photoluminescence, the nanoparticles with the average size of 100 nm have the most reactive oxygen species production upon X-ray irradiation, while the nanoparticles with the average size of 40 nm have the best outcome in the tumor suppression in mice upon X-ray irradiation. For energy, 90 kVp radiation resulted in smaller tumor sizes than 250 kVp or 350 kVp radiation energies. Overall, knowledge of the effect of nanoparticle size and radiation energy on radiation therapy outcomes could be useful for future applications of Cu-Cy nanoparticles.

Investigation of PPIX-Lipo-MnO2 to enhance photodynamic therapy by improving tumor hypoxia.

The efficacy of photodynamic therapy (PDT) is reduced in the context of hypoxic environments. This is problematic, considering that hypoxia is exhibited in the vast majority of malignant tumors. Thus, increasing the concentration of oxygen in malignant tumors improves PDT treatment outcomes. Studies show that MnO2 nanoparticles can produce oxygen when it reacts with endogenous H2O2. Herein, we encapsulated Protoporphyrin IX (PPIX) in the liposome bilayer (PPIX-Lipo), which was then coated with MnO2 nanoparticles to construct PPIX-Lipo-MnO2 (PPIX-Lipo-M) in order to enhance PDT efficacy under tumor hypoxia. The PDT results show that PPIX-Lipo-M was more cytotoxic to breast cancer cells than PPIX-Lipo while under hypoxic conditions, indicating that the production of oxygen gas in hypoxic conditions improved treatment outcomes. Upon encapsulating PPIX into the liposome, the aqueous solubility of PPIX significantly improved. Consequently, the cellular uptake of both PPIX-Lipo and PPIX-Lipo-M also increased significantly compared to that of bare PPIX. Overall, PPIX-Lipo-M has the capacity to act as a therapeutic agent that relieves hypoxia and hence improve PDT efficacy.

A facile method for the synthesis of copper-cysteamine nanoparticles and study of ROS production for cancer treatment.

Copper-cysteamine (Cu-Cy) is a novel sensitizer that can be excited by ultraviolet (UV) light, microwave (MW), ultrasound, and X-rays to generate highly toxic reactive oxygen species (ROS) for cancer cell destruction. The purpose of this study is to present a facile method for the synthesis of Cu-Cy nanoparticles. Interestingly, we were able to decrease both the stirring and heating time by about 24 and 6 times, respectively, thus making Cu-Cy nanoparticles more economical than what was reported before. 1,4-Diazabicylo[2.2.2]octane (DABCO), a well-known singlet oxygen quencher, showed that the majority of ROS produced by Cu-Cy nanoparticles upon UV and MW exposure were singlet oxygen. Moreover, ROS generated by Cu-Cy nanoparticles upon UV and MW exposure were confirmed by a known ROS tracking agent, dihydrorhodamine 123, further serving as an additional piece of evidence that Cu-Cy is a promising ROS generating agent to destroy cancer cells as well as bacteria or viruses by a radical therapeutic approach. Additionally, for the first time, the hydroxyl radical (˙OH) produced by Cu-Cy nanoparticles upon MW activation was proved by a photoluminescence (PL) technique using coumarin as a probe molecule. Remarkably, newly synthesized nanoparticles were found to be much more effective for producing ROS and killing cancer cells, suggesting that the new method may have increased the reactivity of the Cu-Cy nanoparticles due to an overall size reduction. Overall, the new method not only reduced the synthesis time but also enhanced the effectiveness of Cu-Cy nanoparticles for photodynamic therapy.