Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione(GSH) and reac...Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione(GSH) and reactive oxygen species(ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid(LA) and docetaxel(DTX). This mono thioether-linked conjugates(DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue. Our studies demonstrated that the nanoassemblies had uniform particle size, high stability and fast release behavior. DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve(AUC). Compared with DTX solution, the redox dual-responsive nanoassemblies had comparable cytotoxic activity. Besides, the antitumor efficacy was evaluated in mice bearing 4 T1 xenograft. It turned out this nanoassemblies couldenhance anticancer efficacy by increasing the dose because of higher tolerance. Overall, these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy.展开更多
Novel small sulfur heterocyclic quinones(6a,16adihydrobenzo[b]naphtho[2′,3′:5,6][1,4]dithiino[2,3-i]thianthrene-5,7,9,14,16,18-hexaone(4S6Q)and benzo[b]naphtho[2′,3′:5,6][1,4]dithiino[2,3-i]thianthrene-5,9,14,18-t...Novel small sulfur heterocyclic quinones(6a,16adihydrobenzo[b]naphtho[2′,3′:5,6][1,4]dithiino[2,3-i]thianthrene-5,7,9,14,16,18-hexaone(4S6Q)and benzo[b]naphtho[2′,3′:5,6][1,4]dithiino[2,3-i]thianthrene-5,9,14,18-tetraone(4S4Q))are developed by molecule structural design method and as cathode for aqueous zincorganic batteries.The conjugated thioether(–S–)bonds as connected units not only improve the conductivity of compounds but also inhibit their dissolution by both extendedπ-conjugated plane and constructed flexible molecular skeleton.Hence,the Zn//4S6Q and Zn//4S4Q batteries exhibit satisfactory electrochemical performance based on 3.5 mol L-1(M)Zn(ClO4)2electrolyte.For instance,the Zn//4S6Q battery obtains 240 and 208.6 mAh g^(-1)of discharge capacity at 150 mA g^(-1)and 30 A g^(-1),respectively.The excellent rate capability is ascribed to the fast reaction kinetics.This system displays a superlong life of 20,000 cycles with no capacity fading at 3 A g^(-1).Additionally,the H+-storage mechanism of the 4S6Q compound is demonstrated by ex situ analyses and density functional theory calculations.Impressively,the battery can normally work at-60℃benefiting from the anti-freezing electrolyte and maintain a high discharge capacity of 201.7 mAh g^(-1),which is 86.2%of discharge capacity at 25℃.The cutting-edge electrochemical performances of these novel compounds make them alternative electrode materials for Zn-organic batteries.展开更多
基金supported by Liaoning BaiQianWan Talents Program(No.2016921064,China)Nature Science Foundation of Guangdong Province(No.2016A020217017,China)
文摘Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione(GSH) and reactive oxygen species(ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid(LA) and docetaxel(DTX). This mono thioether-linked conjugates(DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue. Our studies demonstrated that the nanoassemblies had uniform particle size, high stability and fast release behavior. DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve(AUC). Compared with DTX solution, the redox dual-responsive nanoassemblies had comparable cytotoxic activity. Besides, the antitumor efficacy was evaluated in mice bearing 4 T1 xenograft. It turned out this nanoassemblies couldenhance anticancer efficacy by increasing the dose because of higher tolerance. Overall, these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy.
基金the National Natural Science Foundation of China(22279063 and 21835004)the National Key R&D Program of China(2016YFB0901500)+1 种基金Ministry of Education of China(B12015 and IRT13R30)the Haihe Laboratory of Sustainable Chemical Transformations for financial support。
文摘Novel small sulfur heterocyclic quinones(6a,16adihydrobenzo[b]naphtho[2′,3′:5,6][1,4]dithiino[2,3-i]thianthrene-5,7,9,14,16,18-hexaone(4S6Q)and benzo[b]naphtho[2′,3′:5,6][1,4]dithiino[2,3-i]thianthrene-5,9,14,18-tetraone(4S4Q))are developed by molecule structural design method and as cathode for aqueous zincorganic batteries.The conjugated thioether(–S–)bonds as connected units not only improve the conductivity of compounds but also inhibit their dissolution by both extendedπ-conjugated plane and constructed flexible molecular skeleton.Hence,the Zn//4S6Q and Zn//4S4Q batteries exhibit satisfactory electrochemical performance based on 3.5 mol L-1(M)Zn(ClO4)2electrolyte.For instance,the Zn//4S6Q battery obtains 240 and 208.6 mAh g^(-1)of discharge capacity at 150 mA g^(-1)and 30 A g^(-1),respectively.The excellent rate capability is ascribed to the fast reaction kinetics.This system displays a superlong life of 20,000 cycles with no capacity fading at 3 A g^(-1).Additionally,the H+-storage mechanism of the 4S6Q compound is demonstrated by ex situ analyses and density functional theory calculations.Impressively,the battery can normally work at-60℃benefiting from the anti-freezing electrolyte and maintain a high discharge capacity of 201.7 mAh g^(-1),which is 86.2%of discharge capacity at 25℃.The cutting-edge electrochemical performances of these novel compounds make them alternative electrode materials for Zn-organic batteries.
文摘为寻找新型杂环活性化合物,通过活性亚结构拼接方法,以硫脲和乙酰丙酮为起始原料合成4,6-二甲基嘧啶-2-硫醇,随后经醚化、肼化、环化和苄基化反应,采用微波促进方法合成了15个新型含嘧啶环结构的1,3,4-噻二唑硫醚类化合物.利用~1H NMR,^(13)C NMR,IR,ESI-MS及元素分析对其结构进行了表征确认.生物活性测试结果表明,在50μg/m L浓度下,部分目标化合物对尖孢炭疽菌、枸杞炭疽菌和草莓炭疽菌具有较好的杀菌活性,其中2-(3-氟苄硫基)-5-(4,6-二甲基嘧啶-2-甲硫基)-1,3,4-噻二唑(7i)对尖孢炭疽菌和草莓炭疽菌的抑制率分别为79.84%和73.46%;若干化合物还表现出良好的抗杜氏利什曼原虫活性,其中2-(2-氟苄硫基)-5-(4,6-二甲基嘧啶-2-甲硫基)-1,3,4-噻二唑(7h)和2-(4-氟苄硫基)-5-(4,6-二甲基嘧啶-2-甲硫基)-1,3,4-噻二唑(7j)的IC50分别为21.3和23.6μg/m L.
