Safety and efficacy of intraperitoneal perfusion with tumor vesicle-encapsulated methotrexate for the treatment of cancerous ascites - an open, randomized and controlled clinical trial

Background:Cancerous ascites is a common and severe complication that occurs in patients with late-stage malignant tumors.The prognosis of cancerous ascites is poor,clinical treatment is difficult and therapeutic outcome is disappointing.In the present study,tumor cell-derived vesicles were used as drug delivery vehicles that encapsulated a chemotherapeutic agent and were perfused into a patients’abdominal cavity to effectively kill the cancer cells in cancerous ascites.Pre-clinical data has demonstrated that tumor vesicles that carry low-dose chemotherapeutics can efficiently eliminate metastatic tumor cells in the abdominal cavity with minimal toxic or adverse effects.When combined,tumor cell-derived vesicles can sensitize tumor cells,which facilitates the entry of chemotherapeutics into tumor cells,thereby enhancing killing of tumor cells and limiting the risk of drug resistance.In this study,we designed a clinical trial to evaluate the safety and efficacy of intraperitoneal perfusion with tumor vesicle-encapsulated methotrexate for the treatment of cancerous ascites.Methods:Sixty patients with cancerous ascites were enrolled in this open,randomized and controlled clinical trial.Participants were randomly assigned a visit number and,according to their visiting order for which a random numerical table was used,were assigned to the trial group or the control group in a 1:1 ratio.The change in ascetic volume was used as the study outcome and adverse events were monitored during the entire length of the study.Conclusion:In this clinical trial,randomization and electronic case report forms were implemented.The trial indicated that tumor vesicle-encapsulated methotrexate was proposed to be a safe and effective method for treating malignant ascites.Our study may provide at the first time evidence for the clinical application of tumor vesicles in tumor therapy.

Eliminating the original cargos of glioblastoma cell-derived small extracellular vesicles for efficient drug delivery to glioblastoma with improved biosafety

Tumor derived small extracellular vesicles(TsEVs)display a great potential as efficient nanocarriers for chemotherapy because of their intrinsic targeting ability.However,the inherited risks of their original cargos(like loaded proteins or RNAs)from parent cancer cells in tumor progression severely hinder the practical application.In this study,a saponin-mediated cargo elimination strategy was established and practiced in glioblastoma(GBM)cell-derived small extracellular vesicles(GBM-sEVs).A high eliminating efficacy of the cargo molecules was confirmed by systematic analysis of the original proteins and RNAs in GBM-sEVs.In addition,the inherited functions of GBM-sEVs to promote GBM progression vanished after saponin treatment.Moreover,the results of cellular uptake analysis and in vivo imaging analysis demonstrated that saponin treatment preserved the homotypic targeting ability of GBM-sEVs.Thus,we developed an efficient nanocarrier with improved biosafety for GBM suppression.Furthermore,doxorubicin(DOX)transported by the saponin-treated GBM-sEVs(sa-GBM-sEVs)displayed an effective tumor suppression in both subcutaneous and orthotopic GBM models of mouse.Collectively,this study provides a feasible way to avoid the potential protumoral risks of TsEVs and can advance the clinical application of TsEVs in chemotherapy.