Thermal accelerated urease-driven hyaluronan-targeted melanin nano-missile for bio-radar detection and chemodrug-free phototherapy.

Polymer-based nanomotors are attracting increasing interest in the biomedical field due to their microscopic size and kinematic properties which support overcoming biological barriers, completing cellular uptake and targeted blasting in limited spaces. However, their applications are limited by the complex viscous physiological environment and lack of sufficient biocompatibility. This manuscript firstly reports a natural melanin nano-missile of MNP@HA-EDA@Urease@AIE PS (MHUA) based on photothermally accelerated urease-driven to achieve chemodrug-free phototherapy. Compared to conventional nano-missiles that only provide driving force, this photothermally accelerated urease-driven nanomotor is independent of chemodrug to maximise biocompatibility, and achieve ideal therapeutic effect through targeted PTT/PDT. In particular, the thermal effect can not only boost the catalytic activity of urease but also achieve ideally anti-tumor effect. In addition, guided by and AIE PS, the nanomotor can generate 1O2 to achieve PDT and be traced in real time serving as an effective fluorescent bio-radar for intracellular self-reporting during cancer treatment. Finally, the targeting ability of MUHA is provided by hyaluronan. Taken together, this MHUA platform provides a simple and effective strategy for target/fluorescence radar detective-guided PTT/PDT combination, and achieves good therapeutic results without chemodrug under thermal accelerated strategy, providing a new idea for the construction of chemodrug-free nanomotor-therapy system.

Photothermal interference urease-powered polydopamine nanomotor for enhanced propulsion and synergistic therapy.

Enzyme-powered nanomotors with active motion have opened a new door in design of biocompatible drug delivery systems for cancer treatment. However, the movement of them still faces huge challenges due to the viscous physiological environment. To address this issue, we developed a photothermal interference (PTI) urease-modified polydopamine (PDA) nanomotor (PDA@HSA@Ur) for deeper-penetration of doxorubicin (DOX) through improved motion. The urease-powered nanomotors can generate self-propulsion via catalyzing decomposition of biocompatible urea into carbon dioxide and ammonia through a self-diffusiophoretic. Meanwhile, when exposed to near-infrared (NIR) laser, the increased temperature of tumors microenvironment from nanomotors can not only induce tumor cell apoptosis but also enhance the biocatalytic activity of urease to improve the motion of nanomotors. Compared to the nanomotors propelled only by urea, PTI nanomotors realize highly effective self-propulsion with improved cellular uptake in vitro. Furthermore, PTI nanomotors display an enhanced anticancer efficiency owing to synergistic photothermal and chemotherapy effect. The PTI reported in this manuscript is the first to provide a thermally assisted method for highly efficient cancer treatment with urease-powered nanomotors in a complex physiological environment through enhanced motion and synergistic therapy.

A Meta-Analysis of Efficacy and Safety of Infliximab for Prevention of Postoperative Recurrence in Patients with Crohn's Disease.

OBJECTIVE: We sought to investigate the efficacy and safety of Infliximab for prevention of postoperative recurrence in patients with Crohn's disease (CD), in a meta-analysis of clinical trial results. METHODS: The Medline, Embase, PubMed, and Web of Science databases were systematically searched for suitable studies. A meta-analysis of enrolled studies was performed to analyze the efficacy of Infliximab on outcomes regarding the prevention of postoperative recurrence of CD. A Galbraith radial plot was used to quantify the heterogeneity. Funnel plot and Egger test were performed to describe the bias of publication. A Forest plot was prepared to indicate the efficacy outcomes. RESULTS: A total of 7 prospective trials were included in our meta-analysis (N=455). The Funnel plot and Egger test showed there was no significant bias in the included publications. The Cochrane collaboration tool indicated that all 7 prospective trials were of high quality. The results of Galbraith radial plot showed that no study was the source of heterogeneity. Compared with the placebo group, Infliximab decreased the rates of endoscopic recurrence (RR =0.421; 95% CI 0.328 to 0.539; p<0.001), and there was a significant reduction in rates of clinical recurrence in the Infliximab-treated group (RR =0.519; 95% CI 0.349 to 0.774; p=0.001). Furthermore, Infliximab treatment did not show adverse effects as other systematic therapeutic drugs, indicating that Infliximab treatment is effective and well tolerated. CONCLUSION: Compared with the controls, Infliximab is a promising therapeutic agent for the management of CD patients.