Copper-Single-Atom Coordinated Nanotherapeutics for Enhanced Sonothermal-Parallel Catalytic Synergistic Cancer Therapy.

Phototherapy and sonotherapy are recognized by scientific medicine as effective strategies for treating certain cancers. However, these strategies have limitations such as an inability to penetrate deeper tissues and overcome the antioxidant tumor microenvironment. In this study, a novel "BH" interfacial-confined coordination strategy to synthesize hyaluronic acid-functionalized single copper atoms dispersed over boron imidazolate framework-derived nanocubes (HA-NC_Cu) to achieve sonothermal-catalytic synergistic therapy is reported. Notably, HA-NC_Cu demonstrates exceptional sonothermal conversion performance under low-intensity ultrasound irradiation, attained through intermolecular lattice vibrations. In addition, it shows promise as an efficient biocatalyst, able to generate high-toxicity hydroxyl radicals in response to tumor-endogenous hydrogen peroxide and glutathione. Density functional theory calculations reveal that the superior parallel catalytic performance of HA-NC_Cu originates from the CuN4 C/B active sites. Both in vitro and in vivo evaluations consistently demonstrate that the sonothermal-catalytic synergistic strategy significantly improves tumor inhibition rate (86.9%) and long-term survival rate (100%). In combination with low-intensity ultrasound irradiation, HA-NC_Cu triggers a dual death pathway of apoptosis and ferroptosis in MDA-MB-231 breast cancer cells, comprehensively limiting primary triple-negative breast cancer. This study highlights the applications of single-atom-coordinated nanotherapeutics in sonothermal-catalytic synergistic therapy, which may create new opportunities in biomedical research.

Different effects of intravenous and local anesthesia in patients undergoing ultrasound-guided radiofrequency ablation of thyroid nodules: a prospective cohort study.

PURPOSE: To compare the efficacy and safety of intravenous anesthesia (IV) with local anesthesia (LA) in patients undergoing ultrasound (US)-guided radiofrequency ablation (RFA) of thyroid nodules. METHODS: 50 patients with American Society of Anesthesiologists classification grades I-II undergoing US-guided thyroid RFA were enrolled and randomly (1:1) divided into IV (conscious sedation with Ramsay Sedation Scale [RSS] scores of 2-3 with an anesthesiologist) and LA (subcutaneous anesthesia with lidocaine without an anesthesiologist) groups. Pre-, intra- and post-procedural blood pressure (BP) (SBP0/DBP0, SBP1/DBP1, and SBP2/DBP2), intra- and post-procedural pain (NRS1 and NRS2), ablated area volume, treatment time and adverse events were analyzed and compared. RESULTS: Age, sex, weight, number, nature, volume of nodules, and SBP0/DBP0 showed no difference between both groups. 11 and 0 patients' SBP1/DBP1 were elevated in the LA and IV groups. NRS1 differed between both groups. 6 patients in the LA group had moderate or severe pain, but none in the IV group. No between-group difference in SBP2/DBP2, NRS2, ablation completion rate and ablated volume was noted. The median procedure duration differed from 1109 (176) s in IV group and 723 (227) s in LA groups. There was no increased incidence of adverse events in IV group. CONCLUSIONS: IV with RSS scores of 2-3 maintained intra-procedural BP and relieved intra-procedural pain better, without affecting the ablation efficacy and increasing complications. Despite increased treatment time, IV is a potential option for patients undergoing US-guided RFA of thyroid nodules.

Infection microenvironment-activated core-shell nanoassemblies for photothermal/chemodynamic synergistic wound therapy and multimodal imaging.

The development of intelligent designs of new antibacterial modalities for diagnosing and treating chronic multidrug-resistant bacterial infections is an urgent need, but achieving the precisive theranostic in response to specific inflammatory microenvironments remains a great challenge. This paper describes our work designing and demonstrating infection microenvironment-activated core-shell Gd-doped Bi2S3@Cu(II) boron imidazolate framework (Bi2S3:Gd@Cu-BIF) nanoassemblies. Upon exposure to a single beam of 808 nm laser, Bi2S3:Gd@Cu-BIF nanoassemblies showed exceptional photothermal conversion (η = 52.6%) and produced several cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, by depleting the intracellular glutathione and in-situ catalyzing the decomposition of endogenous hydrogen peroxide in the inflammatory microenvironment. The broad-spectrum antibacterial properties of nanoassemblies were confirmed to be effective against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) with an inhibition rate of 99.99% in vitro. Additionally, in vivo wound-healing studies revealed that Bi2S3:Gd@Cu-BIF nanoassemblies could serve as an effective wound spray to accelerate healing following MRSA infections via photothermal/chemodynamic (PTT/CDT) synergistic therapy. The effective wound healing rate in the synergistic treatment group was 99.8%, which is higher than the 69.5% wound healing rate in the control group. Furthermore, magnetic resonance and computed tomography dual-modal imaging mediated by Bi2S3:Gd@Cu-BIF nanoassemblies also exhibits promising potential as an integrated diagnostic nanoplatform. Overall, this work provides useful insights for developing all-in-one theranostic nanoplatforms for clinical treatment of drug-resistant bacterial infections. STATEMENT OF SIGNIFICANCE: New treatments and effective diagnostic strategies are critical for fighting drug-resistant bacterial infections. Infection microenvironment-activated Bi2S3@Cu-BIF nanoassemblies can simultaneously increase eigen temperature and generate cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, under near-infrared laser irradiation, achieving the synergistic effect of photothermal and chemodynamic therapy, which has been proven to be highly effective for inhibiting bacterial activity and speeding wound healing from methicillin-resistant Staphylococcus aureus infection. More importantly, the nanoassemblies could enable early precise visualized detection of bacterial abscess using magnetic resonance/computed tomography dual-modal bio-imaging techniques.

Long-term follow-up results of PTMC treated by ultrasound-guided radiofrequency ablation: a retrospective study.

OBJECTIVES: To confirm the long-term efficacy and safety of radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC). METHODS: We retrospectively reviewed data of 102 primary papillary thyroid carcinoma patients (82 women, 20 men; mean age: 43 [19] years) treated with radiofrequency ablation and thyroid-stimulating hormone (TSH) suppression therapy before December 2018. All patients were at high surgical risk or refused surgery. They were followed up at 1, 3, 6, 9, and 12 months and every 6-12 months thereafter using ultrasound and contrast-enhanced ultrasound. The volume and volume reduction ratio was calculated. Recurrence and lymph node or distant metastasis were evaluated. RESULTS: The mean initial tumor diameter was 0.50 (0.29) cm; the mean initial volume was 0.06 (0.09) mL. At 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after RFA, complete resorption rates were 0, 0, 9.8 (10/102), 33.3 (34/102), 91.2 (93/102), 96.1 (98/102), 99 (101/102), 100, and 100%, respectively. Two patients had developed ipsilateral neck lymph node metastasis in regions IV and VI at 30- and 18-month follow-ups, respectively. After RFA, 3/102 patients (2.9%) developed hoarseness-the main side effect. No life-threatening or delayed complications occurred. The TSH value in the initial period was 0.06 (0.02) µIU/mL; the rate of reaching the TSH target was 85.7%. The TSH value at follow-up was 1.47 (0.91) µIU/mL; the compliance rate was 99.3%. CONCLUSIONS: Ultrasound-guided RFA for PTMC is highly effective and safe. RFA can serve as a minimally invasive treatment for PTMC patients who refuse surgery or active surveillance.

Temperature Feedback-Controlled Photothermal/Photodynamic/Chemodynamic Combination Cancer Therapy Based on NaGdF4 :Er,Yb@NaGdF4 :Nd@Cu-BIF Nanoassemblies.

The intelligent design of multifunctional nanoplatforms is critical for cancer therapy. Herein, NaGdF4 :Er,Yb@NaGdF4 :Nd@Cu(II) boron-imidazolate frameworks (denoted as CSNPs@Cu-BIF) nanoassemblies are designed and fabricated. Upon a single 808 nm laser irradiation, the nanoassemblies not only show the outstanding photothermal conversion capacity (η = 41.7%) but also generate cytotoxic reactive oxygen species through an in situ Fenton-like reaction and fluorescence resonance energy transfer. Importantly, the nanoassemblies simultaneously introduce remarkable antitumor efficacy via photothermal/photodynamic/chemodynamic combination therapy both in vitro and in vivo. To improve the therapeutic effect of solid tumor ablation, it is highly desirable to monitor the treatment process in real-time. Multiclinical imaging modalities of ultrasonography are employed to systematically investigate the ablation mechanism of solid tumors in vivo. Furthermore, the significant difference between the eigen temperature of CSNPs@Cu-BIF nanoassemblies obtained by the temperature-sensitive emission bands signal changes and the apparent temperature recorded by the thermal imaging camera is 14.55 K at equilibrium. This current work therefore supplies an alternative strategy in temperature feedback-controlled accurate cancer therapy.

In-situ synthesis of metal nanoparticles@metal-organic frameworks: Highly effective catalytic performance and synergistic antimicrobial activity.

M-NP@Zn-BIF (M-NP = Ag or Cu nanoparticle; Zn-BIF is a zinc-based boron imidazolate framework, Zn2(BH(2-mim)3)2(obb); 2-mim = 2-methylimidazole; obb = 4,4'-oxybis(benzoate)) composites were successfully in-situ synthesized by utilizing the reducing ability of the BH bond contained in the Zn-BIF at room temperature without any additional chemical reduction reagents. These composites (225 µg/mL) exhibited excellent catalytic activity to convert 4-nitrophenol to 4-aminophenol in 2.5 min and 6 min with a conversion rate of 99.9 %, respectively. In addition, Ag@Zn-BIF (50 µg/mL) showed highly synergistic antibacterial activity against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) with a bactericidal rate of approximately 99.9 %. An antibacterial mechanism was proposed for the generation of intracellular reactive oxygen species (ROS) levels. Superoxide radicals (O2-) and hydroxyl radicals (OH) formed during the antibacterial process were shown to accelerate the death of bacteria. They also exhibited highly photocatalytic activity for Rhodamine B (RhB). When the concentration of the composites is 1000 µg/mL, the photocatalytic efficiency of Ag@Zn-BIF and Cu@Zn-BIF increased by 31.62 and 18.13 times compared with Zn-BIF, respectively. All in all, this study developed a simple and versatile integrated platform for the removal of nitrophenols, organic dyes, and the effective inactivation of bacteria in water.