In order to improve the targeting and availability of liposomes to cancer cells,the temperature sensitivity of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine(DPPC)and the pH sensitivity of PASP in PASP-g-C8 are incorpora...In order to improve the targeting and availability of liposomes to cancer cells,the temperature sensitivity of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine(DPPC)and the pH sensitivity of PASP in PASP-g-C8 are incorporated in a drug delivery system.A composite pH-temperature dual-sensitive liposomes(CPTLPs)was obtained as an efficient drug delivery system.The bionic bilayer is self-assembled by cholesterol/cationic temperature-sensitive lipids as base layer and pH-sensitive octylamine grafted poly aspartic acid(PASP-g-C8)as anchors coated outside.Cytarabine(CYT)was chosen as a model drug.SEM and DLS were used to observe the morphology characteristics of CPTLPs in different micro environment.The results demonstrated that the CPTLPs remained active in both normal(pH7.4 and 37°C)and tumor tissues(pH 5.0 and 42°C).As a stable colloidal system,the zeta potential of CPTSLs was−41.6 mV.In vitro drug-release experiments,the CTY encapsulated dual-sensitive liposomes,CPTSLs(+),not only have significant pH-temperature sensitivity but have more prolonged release in vitro than control groups.MTT tests results indicated that the cell apoptotic effects induced by CPTSLs(+)were nearly 30%higher than the naked drug CTY in HepG2 cells,and 20%lower apoptotic in vero cells.The CPTSLs(+)sustained a stable emulsion form,less toxic effects on normal cells,and exhibited a good pH-temperature sensitivity,thus expected to be a promising tumor targeting drug delivery.展开更多
Regulating brain iron metabolism and reducing neuronal ferroptosis is proven to be a potential method for treating Alzheimer's disease(AD).However,gastric juice has a pH of 1.1—2.2 where a large number of interfe...Regulating brain iron metabolism and reducing neuronal ferroptosis is proven to be a potential method for treating Alzheimer's disease(AD).However,gastric juice has a pH of 1.1—2.2 where a large number of interfering ions are dissociated from the food,which in turn causes traditional oral iron chelators to be saturated and inactivated.Herein,poly(4-vinylbenzoic acid)polymer chains were introduced as guided by Fe3+ion template into the porous network(TpPa-1)via molecularly imprinted technology to obtain porous iron chelators,COOH@TpPa-1.The COOH@TpPa-1 maintains a multiple hydrogen bonding structure to block the channels in the stomach(pH~1.1—2.2)with a strongly acidic environment,so just a small amount of active sites have been occupied.As COOH@TpPa-1 enters the colon,the alkaline environment disrupts the original hydrogen-bonded structure and forms anionic fragments,the bonding affinity for Fe^(3+)ions was~4.0 times that in the stomach,and also gave a high selective coefficient 4.2 times higher than that of conventional iron chelators.These designable"on"and"off"states promote the effective enrichment of iron ions within the colon by the porous chelator and produce a favorable therapeutic effect on Alzheimer's symptoms caused by ferroptosis in mice.展开更多
基金The financial support from the National Natural Science Foundation of China(21838001,31961133018,21525625)National Key R&D Program of China(2018YFA0902200)is acknowledged.
文摘In order to improve the targeting and availability of liposomes to cancer cells,the temperature sensitivity of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine(DPPC)and the pH sensitivity of PASP in PASP-g-C8 are incorporated in a drug delivery system.A composite pH-temperature dual-sensitive liposomes(CPTLPs)was obtained as an efficient drug delivery system.The bionic bilayer is self-assembled by cholesterol/cationic temperature-sensitive lipids as base layer and pH-sensitive octylamine grafted poly aspartic acid(PASP-g-C8)as anchors coated outside.Cytarabine(CYT)was chosen as a model drug.SEM and DLS were used to observe the morphology characteristics of CPTLPs in different micro environment.The results demonstrated that the CPTLPs remained active in both normal(pH7.4 and 37°C)and tumor tissues(pH 5.0 and 42°C).As a stable colloidal system,the zeta potential of CPTSLs was−41.6 mV.In vitro drug-release experiments,the CTY encapsulated dual-sensitive liposomes,CPTSLs(+),not only have significant pH-temperature sensitivity but have more prolonged release in vitro than control groups.MTT tests results indicated that the cell apoptotic effects induced by CPTSLs(+)were nearly 30%higher than the naked drug CTY in HepG2 cells,and 20%lower apoptotic in vero cells.The CPTSLs(+)sustained a stable emulsion form,less toxic effects on normal cells,and exhibited a good pH-temperature sensitivity,thus expected to be a promising tumor targeting drug delivery.
基金supported by the National Key R&D Program of China(Grant No.2022YFB3805902)the National Natural Science Foundation of China(Grant Nos.22322501,52204389,21975039,and 22077118)+4 种基金the Fundamental Research Funds for the Central Universities,Excellent Youth Team Program(grant No.2412023YQ001)the China Postdoctoral Science Foundation(2023T160261)the Finance Special Project on Medical and Health Talents of the Finance Department of Jilin Province(JLSWSRCZX2023-52)WBE Liver Fibrosis Foundation(No.2020009)Jilin Province Science and Technology Development Plan Project(YDZJ202401202ZYTS).
文摘Regulating brain iron metabolism and reducing neuronal ferroptosis is proven to be a potential method for treating Alzheimer's disease(AD).However,gastric juice has a pH of 1.1—2.2 where a large number of interfering ions are dissociated from the food,which in turn causes traditional oral iron chelators to be saturated and inactivated.Herein,poly(4-vinylbenzoic acid)polymer chains were introduced as guided by Fe3+ion template into the porous network(TpPa-1)via molecularly imprinted technology to obtain porous iron chelators,COOH@TpPa-1.The COOH@TpPa-1 maintains a multiple hydrogen bonding structure to block the channels in the stomach(pH~1.1—2.2)with a strongly acidic environment,so just a small amount of active sites have been occupied.As COOH@TpPa-1 enters the colon,the alkaline environment disrupts the original hydrogen-bonded structure and forms anionic fragments,the bonding affinity for Fe^(3+)ions was~4.0 times that in the stomach,and also gave a high selective coefficient 4.2 times higher than that of conventional iron chelators.These designable"on"and"off"states promote the effective enrichment of iron ions within the colon by the porous chelator and produce a favorable therapeutic effect on Alzheimer's symptoms caused by ferroptosis in mice.
