A facile boronophenylalanine modified polydopamine dual drug-loaded nanoparticles for enhanced anti-tumor immune response in hepatocellular carcinoma comprehensive treatment.

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence.

Efficacy and Safety Assessment of Rivaroxaban for the Treatment of Cerebral Venous Sinus Thrombosis in a Chinese Population.

We aimed to investigate the efficacy and safety of rivaroxaban for acute and long-term management of cerebral venous sinus thrombosis (CVST). This study reviewed CVST-diagnosed patients admitted to the First Affiliated Hospital of Guangxi Medical University from January 2015 to December 2020. The primary outcome was a composite of recurrent thrombosis or major bleeding events. The secondary efficacy outcomes included a disease recovery time (DRT) presenting the time from admission to the endpoint as recovery (the modified Rankin scale [mRS] score [0-1]) within 30 and 90 days, and length of hospital stay (LHS). Patients treated with rivaroxaban (38) and warfarin (45) were enrolled in the final analysis. The primary outcome had no significant difference (5.3% vs 11.1%, P = .576) between the 2 groups. The secondary efficacy outcome regarding the median 30-d DRT was 17 days (95% confidence interval [CI], 14.6-19.4) in the rivaroxaban group, compared with 26.0 days (95% CI, 16.8-35.2) in the warfarin group (hazard ratio, 1.806; 95% CI, 1.051-3.103; log-rank P = .026). Two groups have a significant difference in LHS (P = .041). Patients with cerebral edema, intracerebral hemorrhage, and mild/moderate disability (admission mRS score [2-3]) treated with rivaroxaban recovered faster than those with warfarin (log-rank P < .05). Patients with cerebral edema, intracerebral hemorrhage, and mild/moderate disability treated with rivaroxaban had a shorter recovery time than those treated with warfarin within 1 month from admission, indicating that rivaroxaban a promising convenient therapy for CVST, helping them speedily restore social functions.

Temporally Controlled Photothermal/Photodynamic and Combined Therapy for Overcoming Multidrug Resistance of Cancer by Polydopamine Nanoclustered Micelles.

Currently, the simple integration of multiple therapeutic agents within a single nanostructure for combating multidrug resistance (MDR) tumors yet remains a challenge. Herein, we report a photoresponsive nanocluster (NC) system prepared by installing polydopamine (PDA) nanoparticle clusters on the surface of d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) (a drug efflux inhibitor) micelles solubilized with IR780 (a photosensitizer) to achieve a combined chemotherapy (CT)/photothermal therapy (PTT)/photodynamic therapy (PDT) for drug-resistant breast cancer. Mediated by the fluorescence resonance energy transfer and radical scavenging properties of PDA, NC shows prominently quenched fluorescence emission (∼78%) and inhibited singlet oxygen generation (∼67%) upon exposure to near-infrared (NIR) light (808 nm, 0.5 W cm-2), favoring a highly efficient PTT module. Meanwhile, the photothermal heat can also boost the release of doxorubicin hydrochloride whose intracellular accumulation can be greatly enhanced by TPGS. Interestingly, the first NIR irradiation and subsequent incubation (∼24 h) can induce the gradual relocation and disintegration of PDA nanoparticles, thereby leading to activated PDT therapy under the second irradiation. Upon the temporally controlled sequential application of PTT/PDT, the developed NC exhibited a great potential to treat MDR cancer both in vitro and in vivo. These findings suggest that complementary interactions among PTT/PDT/CT modalities can enhance the efficiency of the combined therapy for MDR tumor.