Tumor-targeting attenuated Salmonella could induce certain antitumor therapeutic effect through its proliferation characteristic and the consequent activated immune response,while host defense cells represented by neu...Tumor-targeting attenuated Salmonella could induce certain antitumor therapeutic effect through its proliferation characteristic and the consequent activated immune response,while host defense cells represented by neutrophils would trap and eliminate these invading bacteria via producing excess hydrogen peroxide(H_(2)O_(2))-including reactive oxygen species in the bacteriainfected tumor,thereby impairing the efficacy of the bacteria treatment of tumor.Herein,we attempt to combine bacteria treatment and oxygen-dependent radioimmunotherapy of tumor through injection of neutrophil-targeted nano-catalase into the bacteria-treated mice for perfect tumor treatment outcome.Denatured albumin is used to coat catalase and deliver it to the neutrophils infiltrated in bacteria-infected tumor tissue.Taking advantage of the generating H_(2)O_(2)by neutrophils,easily-diffused oxygen is produced and spread the whole tumor under the catalysis of nano-enzyme,leading to enhanced radiotherapy of hypoxic tumor cells.Moreover,the optimized tumor microenvironment,synergistically caused by potent immune-stimulation of bacteria,generating oxygen and tumor radiotherapy,would boost the antitumor immunity.This novel combination therapy strategy holds great promise to provide new ideas for future clinical cancer treatment.展开更多
基金the National Natural Science Foundation of China(Nos.32171382,U1932208 U2032134,and 31900986)the Project of State Key Laboratory of Radiation Medicine and Protection,Soochow University(No.GZK1202110)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Tumor-targeting attenuated Salmonella could induce certain antitumor therapeutic effect through its proliferation characteristic and the consequent activated immune response,while host defense cells represented by neutrophils would trap and eliminate these invading bacteria via producing excess hydrogen peroxide(H_(2)O_(2))-including reactive oxygen species in the bacteriainfected tumor,thereby impairing the efficacy of the bacteria treatment of tumor.Herein,we attempt to combine bacteria treatment and oxygen-dependent radioimmunotherapy of tumor through injection of neutrophil-targeted nano-catalase into the bacteria-treated mice for perfect tumor treatment outcome.Denatured albumin is used to coat catalase and deliver it to the neutrophils infiltrated in bacteria-infected tumor tissue.Taking advantage of the generating H_(2)O_(2)by neutrophils,easily-diffused oxygen is produced and spread the whole tumor under the catalysis of nano-enzyme,leading to enhanced radiotherapy of hypoxic tumor cells.Moreover,the optimized tumor microenvironment,synergistically caused by potent immune-stimulation of bacteria,generating oxygen and tumor radiotherapy,would boost the antitumor immunity.This novel combination therapy strategy holds great promise to provide new ideas for future clinical cancer treatment.
