The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials under...The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials underway,some researchers hold the following views:“humans are nearing the first commercial live bacteria therapeutic.”However,the facultative anaerobe Salmonella typhimurium VNP20009,which is particularly safe and shows anticancer effects in preclinical studies,had failed in a phase I clinical trial due to low tumor regression and undesired dose-dependent side effects.This is almost certain to disappoint people’s inflated expectations,but it is noted that recent stateof-the-art research has turned attention to bacteria-mediated synergistic cancer therapy(BMSCT).In this review,the foundation of bacteria-mediated bio-therapy is outlined.Then,we summarize the potential benefits and challenges of bacterial bio-therapy in combination with different traditional anticancer therapeutic modalities(chemotherapy,photothermal therapy,reactive oxygen and nitrogen species therapy,immunotherapy,or prodrug-activating therapy)in the past 5 years.Next,we discuss multiple administration routes of BMSCT,highlighting potentiated antitumor responses and avoidance of potential side effects.Finally,we envision the opportunities and challenges for BMSCT development,with the purpose of inspiring medicinal scientists to widely utilize the microbiome approach in patient populations.展开更多
Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacter...Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacteriophage, which constitutes a type of virus that can kill bacteria, is a promising alternative strategy against antibiotic-resistant bacterial infections. Although bacteriophage therapy was first used nearly a century ago, its development came to a standstill after introducing the antibiotics. Nowadays, with the rise in antibiotic resistance, bacteriophage therapy is in the spotlight again.As bacteriophage therapy is safe and has significant anti-bacterial activity, some specific types of bacteriophages(such as bacteriophage phi X174 and Pyo bacteriophage complex liquid) entered into phase Ⅲ clinical trials. Herein, we review the key points of the antibiotic resistance crisis and illustrate the factors that support the renewal of bacteriophage applications. By summarizing recent state-of-the-art studies and clinical data on bacteriophage treatment, we introduced(i) the pharmacological mechanisms and advantages of antibacterial bacteriophages,(ii) bacteriophage preparations with clinical potential and bacteriophage-derived anti-bacterial treatment strategies, and(iii) bacteriophage therapeutics aimed at multiple infection types and infection-induced cancer treatments. Finally, we highlighted the challenges and critical perspectives of bacteriophage therapy for future clinical development.展开更多
A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenou...A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier.Herein,we report an albumin-bound tumor redoxresponsive paclitaxel prodrugs nano-delivery strategy.Using diverse linkages(thioether bond and disulfide bond),paclitaxel(PTX)was conjugated with an albumin-binding maleimide(MAL)functional group.These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles(NPs)in aqueous solution without any excipients.By immediately binding to blood circulating albumin after intravenous administration,NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo,facilitating PTX prodrugs accumulation in the tumor region via albumin receptormediated active targeting.The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells.Moreover,disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo.This simple and facile strategy integrates the biomimetic characteristic of albumin,tumor redox-responsive on-demand drug release,and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.展开更多
基金Supported by National Natural Science Foundation of China,No.81773656Liaoning Revitalization Talents Program,No.XLYC1808017Shenyang Youth Science and Technology Innovation Talents Program,No.RC190454.
文摘The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials underway,some researchers hold the following views:“humans are nearing the first commercial live bacteria therapeutic.”However,the facultative anaerobe Salmonella typhimurium VNP20009,which is particularly safe and shows anticancer effects in preclinical studies,had failed in a phase I clinical trial due to low tumor regression and undesired dose-dependent side effects.This is almost certain to disappoint people’s inflated expectations,but it is noted that recent stateof-the-art research has turned attention to bacteria-mediated synergistic cancer therapy(BMSCT).In this review,the foundation of bacteria-mediated bio-therapy is outlined.Then,we summarize the potential benefits and challenges of bacterial bio-therapy in combination with different traditional anticancer therapeutic modalities(chemotherapy,photothermal therapy,reactive oxygen and nitrogen species therapy,immunotherapy,or prodrug-activating therapy)in the past 5 years.Next,we discuss multiple administration routes of BMSCT,highlighting potentiated antitumor responses and avoidance of potential side effects.Finally,we envision the opportunities and challenges for BMSCT development,with the purpose of inspiring medicinal scientists to widely utilize the microbiome approach in patient populations.
基金This work was supported by National Key R&D Program of China(No.2021YFA0909900)National Natural Science Foundation of China(Nos.82073777 and 81803442)+3 种基金Liaoning Revitalization Talents Program(No.XLYC180801)Shenyang Youth Science and Technology Innovation Talents Program(No.RC190454)China Postdoctoral Science Foundation(No.2020M680986)General Project of Liaoning Provincial Department of Education(Nos.LJKZ0927 and LJKQZ2021034).
文摘Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacteriophage, which constitutes a type of virus that can kill bacteria, is a promising alternative strategy against antibiotic-resistant bacterial infections. Although bacteriophage therapy was first used nearly a century ago, its development came to a standstill after introducing the antibiotics. Nowadays, with the rise in antibiotic resistance, bacteriophage therapy is in the spotlight again.As bacteriophage therapy is safe and has significant anti-bacterial activity, some specific types of bacteriophages(such as bacteriophage phi X174 and Pyo bacteriophage complex liquid) entered into phase Ⅲ clinical trials. Herein, we review the key points of the antibiotic resistance crisis and illustrate the factors that support the renewal of bacteriophage applications. By summarizing recent state-of-the-art studies and clinical data on bacteriophage treatment, we introduced(i) the pharmacological mechanisms and advantages of antibacterial bacteriophages,(ii) bacteriophage preparations with clinical potential and bacteriophage-derived anti-bacterial treatment strategies, and(iii) bacteriophage therapeutics aimed at multiple infection types and infection-induced cancer treatments. Finally, we highlighted the challenges and critical perspectives of bacteriophage therapy for future clinical development.
基金supported by National Natural Science Foundation of China(No.81773656 and U1608283)Liaoning Revitalization Talents Program(No XLYC1808017,China)+2 种基金Key projects of Technology bureau in Shenyang(No.18400408,China)Key projects of Liaoning Province Department of Education(No.2017LZD03,China)111 Project(D20029,China)
文摘A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier.Herein,we report an albumin-bound tumor redoxresponsive paclitaxel prodrugs nano-delivery strategy.Using diverse linkages(thioether bond and disulfide bond),paclitaxel(PTX)was conjugated with an albumin-binding maleimide(MAL)functional group.These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles(NPs)in aqueous solution without any excipients.By immediately binding to blood circulating albumin after intravenous administration,NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo,facilitating PTX prodrugs accumulation in the tumor region via albumin receptormediated active targeting.The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells.Moreover,disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo.This simple and facile strategy integrates the biomimetic characteristic of albumin,tumor redox-responsive on-demand drug release,and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.
