Protein-based nanocarriers with inherent biocompatibility have been widely served as building blocks to construct versatile therapeutic nanoplatforms. Herein, bovine serum albumin-iridium oxide nanoparticles (denoted BSA-IrO2 NPs) are successfully synthesized via one-step biomineralization approach. The BSA-IrO2 NPs exhibits uniform size (40 nm), superb biocompatibility and high drug loading capacity for doxorubicin (27.4 wt%). Under near-infrared (NIR) laser irradiation, the as-prepared BSA-IrO2 NPs exhibited high photothermal conversion ability (54.3%) and good photostability. The in vitro drug release experiments displayed pH and NIR laser -triggered DOX release profiles, which could enhance the therapeutic anticancer effect. By utilizing this DOX loaded nanoplatform, effective synergistic chemo-photothermal therapy against human osteosarcoma can be realized, which has been systematically verified both in vitro and in vivo. Notably, in vivo pharmacokinetics studies showed that BSA-IrO2@DOX had prolonged blood circulation time due to the BSA component can improve the stealthiness of the nanoparticles during the blood circulation. Meanwhile, in vitro and in vivo toxicity studies demonstrated that the BSA-IrO2 NPs can act as biocompatible agents for drug delivery and cancer therapy. Therefore, this work presents a biomineralized iridium-based NPs with remarkable features and be used as a very potential therapeutic nanoplatform for cancer treatment.

Background: Stenotrophomonas maltophilia (S. maltophilia) is a multidrug-resistant gram-negative bacillus that is known to be an opportunistic pathogen, particularly in a hospital environment. The infection has a high morbidity and mortality. Sulfamethoxazoletrimethoprim (SXT) is the first-line agent recommended for its treatment. The global spread of dihydropteroate synthase (sul) genes has resulted in an increased resistance rate. However, the appropriate therapy for infections caused by sul-carrying S. maltophilia has not yet been established. Objective: Our study aimed to identify the optimal antibiotic combinations that could both show high antibacterial activity against sul-carrying S. maltophilia and the ability to prevent the emergence of resistance at clinical dosage regimens. Methods: Time-killing experiments and mutant prevention concentration (MPC) experiments were conducted to evaluate the antibacterial effect and ability to prevent resistance to minocycline, tigecycline, moxifloxacin, and ticarcillin/clavulanic acid (T/K), both alone and in combination, at clinically relevant antimicrobial concentrations. Results: Minocycline, tigecycline, and T/K all exhibited bacteriostatic activity to sul-carrying S. maltophilia. The combination of minocycline plus T/K and tigecycline plus T/K neither enhanced the bactericidal ability nor prevented drug-resistant mutations. Moxifloxacin, at 2 mg/L, showed good bactericidal activity to most S. maltophilia, but bacterial regrowth at 24 h was observed in two strains. When combined with T/K, moxifloxacin showed good bactericidal activity in all moxifloxacin-sensitive strains. The concentrations of moxifloxacin alone were lower than most MPCs of the tested sul-carrying strains. When combined with T/K, the mean steady-state concentrations (MSC) of moxifloxacin could prevent 70% of resistance, and the peak concentration (C max ) prevented 95% of resistance. Conclusion:The combination of moxifloxacin and T/K can achieve a good in vitro bactericidal effect and prevent the emergence of resistance at clinical dosage regimens, and may be an optimal therapeutic strategy for S. maltophilia infections, especially for vulnerable immunocompromised and critically ill patients.

Purpose Heat shock proteins (HSPs) play important roles in oncogenesis and malignant progression. HSPB11 is highly expressed in many malignant tumors, but research on its role in hepatocellular carcinoma (HCC) is insufficient. Patients and Methods A comprehensive analysis of HSPB11 in HCC was performed based on data of patients with HCC and those from online public databases. Results HSPB11 was overexpressed in HCC, with a high discrimination ability between tumor and normal tissues (area under the curve =0.923). HSPB11 overexpression correlated with advanced tumor stage, poorer tumor differentiation, and worse prognosis and was an independent risk factor for HCC prognosis. The nomogram and calibration models composed of HSPB11, T stage, and M stage had good abilities to predict the 1-, 3-, and 5-year survival rates of patients. HSPB11 was determined to be involved in multiple oncogenic processes, including cell cycle checkpoints, the G2M checkpoint, E2F targets, Rho GTPases, and KRAS signaling. HSPB11 expression was related to immune cell infiltration, especially that of Th2 cells and dendritic cells. Conclusion HSPB11 is involved in oncogenesis and immune regulation in HCC and is a potential prognostic biomarker and therapeutic target.