Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting...Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting against these stealthy bacteria has been a longstanding challenge.Here,a system of stimuli-responsive lactoferrin(Lf)nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin(Rif)(Rif@Lf NPs)for enhanced infection therapy through targeted elimination of intracellular bacteria.Compared to Rif@BSA NPs,the Rif@Lf NPs can specifically target macrophages infected by bacteria,thus increasing the accumulation of Rif within macrophages.Subsequently,Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redoxresponsive manner.Combined with the antibacterial activities of Lf and Rif,the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms.As a result,the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection,sepsis,and bacterial keratitis.Taken together,the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.展开更多
A mathematical model describing the antiretroviral therapy of Enfuvirtide on HIV-1 patients is developed. The effect of Enfuvirtide （formerly called T-20） by impulsive differential equations is modeled by two differ...A mathematical model describing the antiretroviral therapy of Enfuvirtide on HIV-1 patients is developed. The effect of Enfuvirtide （formerly called T-20） by impulsive differential equations is modeled by two different drug elimination kinetics, the first-order elimination kinetics and the Michaelis-Menten elimination kinetics. The model is a non-autonomous system of differential equations. For a time-dependent system, the disease-free equilibrium is mainly studied. Its stability, when the therapy is taken with perfect adherence, is obtained. To ensure the disease-free equilibrium remains stable, the analytical thresholds for dosage and dosing intervals are determined. The effects of super- vised treatment interruption are also explored. It is shown that the supervised treatment interruption can be worse than no therapy at all.展开更多
Establishing a pre-metastatic niche(PMN)in secondary organs is a prerequisite for cancer metastases.Despite advances in cancer therapy,the efficient inhibition of PMN formation remains a clinical challenge.Recent adva...Establishing a pre-metastatic niche(PMN)in secondary organs is a prerequisite for cancer metastases.Despite advances in cancer therapy,the efficient inhibition of PMN formation remains a clinical challenge.Recent advances in understanding the specific characteristics of PMN and advances in nanotechnology have provided hope for manipulating their microenvironments.A series of nanostrategies have been designed to eliminate the PMN,including the removal of pro-metastatic exosomes from the bloodstream for excretion via the intestines,the targeting and scavenging of myeloid-derived suppressor cells,fibroblasts,and critical extracellular matrix components,and the elimination of circulating tumor cells prior to colonization in distant organs.This review summarizes the underlying mechanisms of PMN formation,highlights the anti-PMN efficacy of currently reported nanostrategies,and underlines the unresolved questions.展开更多
基金support from the National Natural Science Foundation of China(Nos.22275081,82372117)Guangzhou Science and Technology Bureau(202206010068)China Postdoctoral Science Foundation(2022M711532 and 2022T150302).
文摘Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting against these stealthy bacteria has been a longstanding challenge.Here,a system of stimuli-responsive lactoferrin(Lf)nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin(Rif)(Rif@Lf NPs)for enhanced infection therapy through targeted elimination of intracellular bacteria.Compared to Rif@BSA NPs,the Rif@Lf NPs can specifically target macrophages infected by bacteria,thus increasing the accumulation of Rif within macrophages.Subsequently,Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redoxresponsive manner.Combined with the antibacterial activities of Lf and Rif,the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms.As a result,the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection,sepsis,and bacterial keratitis.Taken together,the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.
基金supported by the National Natural Science Foundation of China(No.11072136)the Shanghai Leading Academic Discipline Project(No.S30104)+2 种基金the International Development Research Center of Canada(No.104519-010)the Ministry of Health of China(No.2009DFB30420)the State Key Laboratory for Infectious Disease Prevention and Control of China(No.2008SKLID101)
文摘A mathematical model describing the antiretroviral therapy of Enfuvirtide on HIV-1 patients is developed. The effect of Enfuvirtide （formerly called T-20） by impulsive differential equations is modeled by two different drug elimination kinetics, the first-order elimination kinetics and the Michaelis-Menten elimination kinetics. The model is a non-autonomous system of differential equations. For a time-dependent system, the disease-free equilibrium is mainly studied. Its stability, when the therapy is taken with perfect adherence, is obtained. To ensure the disease-free equilibrium remains stable, the analytical thresholds for dosage and dosing intervals are determined. The effects of super- vised treatment interruption are also explored. It is shown that the supervised treatment interruption can be worse than no therapy at all.
基金the National Natural Science Foundation of China(Nos.82325029,U23A20591,U22A20156,52273158,82102845,52173149,and 52022095)the Shandong Province Innovation Platform Projects(No.2021LCZX04)+3 种基金the Academic Promotion Program of Shandong First Medical University(No.2019LJ004)the Shandong Natural Science Foundation Major Basic Research Project(No.ZR2022ZD31)the Shandong Province Traditional Chinese Medicine Science and Technology Program(No.Z-2022075)the Shandong Province Natural Science Foundation(No.ZR2020MH090).
文摘Establishing a pre-metastatic niche(PMN)in secondary organs is a prerequisite for cancer metastases.Despite advances in cancer therapy,the efficient inhibition of PMN formation remains a clinical challenge.Recent advances in understanding the specific characteristics of PMN and advances in nanotechnology have provided hope for manipulating their microenvironments.A series of nanostrategies have been designed to eliminate the PMN,including the removal of pro-metastatic exosomes from the bloodstream for excretion via the intestines,the targeting and scavenging of myeloid-derived suppressor cells,fibroblasts,and critical extracellular matrix components,and the elimination of circulating tumor cells prior to colonization in distant organs.This review summarizes the underlying mechanisms of PMN formation,highlights the anti-PMN efficacy of currently reported nanostrategies,and underlines the unresolved questions.
