ABSTRACT
Chemotherapy is an important adjuvant treatment of glioma, while the efficacy is far from satisfactory, due not only to the biological barriers of blood‒brain barrier (BBB) and blood‒tumor barrier (BTB) but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as up-regulation of P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, glioma targeting, and chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment, including macrophages repolarization and neutrophils infiltration. Specifically, tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue of the surface pathogen-associated molecular patterns derived from native bacteria, OMVs/DOX could be selectively recognized by neutrophils, thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect. Moreover, the P-gp expression on tumor cells was silenced by bacteria type III secretion effector to sensitize the efficacy of DOX, resulting in complete tumor eradication with 100% survival of all treated mice. In addition, the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk, and cardiotoxicity of DOX was also avoided, achieving excellent compatibility. This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.
ABSTRACT
【Objective】 To investigate the safety and efficacy of flexible vacuum aspiration ureteral access sheath in ureteroscopic lithotripsy in the treatment of renal and upper ureteral calculi. 【Methods】 Clinical data of 41 cases treated in our hospital were retrospectively analyzed, including 20 cases treated with flexible vacuum aspiration ureteral access sheath (experimental group), and 21 cases treated with traditional ureteral access sheath (control group). The stone-clearance rate, operation time, postoperative fever (T>37.5 ℃), length of hospital stay and hospitalization costs were compared between the two groups. 【Results】 All operations were successful. The experimental group had significantly shorter operation time than the control group [(54.0±19.8) min vs. (76.6±20.1) min, P0.05). 【Conclusion】 Flexible vacuum aspiration ureteral access sheath in flexible ureteroscopic lithotripsy can shorten the operation time, improve stone-clearance rate and reduce incidence of postoperative fever, which is worth promoting.
ABSTRACT
The combination of chemotherapy and photodynamic therapy provides a promising approach for enhanced tumor eradication by overcoming the limitations of each individual therapeutic modality. However, tumor is pathologically featured with extreme hypoxia together with the adaptable overexpression of anti-oxidants, such as glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-photodynamic therapy. In our system, a novel multi-functional nanosystem based on MnO