A polymeric polyethylenimine(PEI)-based prodrug of anticancer doxorubicin(DOX)(PEI-hyd-DOX) was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug co-delivery in response to the intracellular acid microenvironments in the late endosome/lysosome compartments. The cytotoxicity of PEI-hyd-DOX was evaluated by the MTT assay and the cellular uptake was monitored using confocal laser scanning microscopy. The polymeric prodrug can respond with a high sensitivity to the specific acid condition inside cells, thus permitting the precise biocontrol over intracellular drug liberation with high drug efficacy. The chemical attachment of drug molecules also led to the relatively reduced toxicity and the enhanced transfection efficiency compared with parent PEI. The resulting data adumbrated the potential of PEI-hyd-DOX to co-deliver DOX and therapeutic gene for the combination of chemotherapy and gene therapy.
采用连续原子转移自由基聚合途径制备了两亲性三嵌段聚合物聚乙二醇-聚甲基丙烯酸N,N-二甲氨基乙酯-聚甲基丙烯酸正丁酯(PEG-PDMAEMA-PBMA),利用核磁共振氢谱(1 H NMR)和凝胶渗透色谱(GPC)对聚合物结构及分子量进行了表征.动态光散射(DLS)和透射电镜(TEM)结果证实该聚合物的自组装行为具有pH敏感性.通过改变水溶液的pH值可以精确地调控聚合物的自组装行为,从而获得胶束、纳米球、大囊泡和小囊泡等多种自组装结构.这些自组装结构的形成与PDMAEMA链段的质子化程度和聚合物的亲疏水平衡有关.
Based on specific host-guest interactions between amine-modified [3-cyclodextrin （CD-TAEA） and functional adamantane （AD） derivatives, a module-template strategy has been proposed for the construction of low-molecular-weight cationic assem- blies for gene transport. This strategy offers great flexibility in terms of the introduction of mono- or multi-functionality by the inclusion of one or more adamantane-based modules with the desired functionalities. As proof of concept, phenylboronic acid （PB） containing adamantane （PB-AD） was used as a model module in the hope of offering enhanced cytosolic delivery in con- sideration of the special affinity of PB groups with cell membranes. The physicochemical properties of the complexes formed with plasmid DNA, such as particle size, zeta potential and morphology were investigated. Confocal laser scanning microsco- py and flow cytometry experiments demonstrated the important contribution of the functional PB-AD module to the consider- ably enhanced intracellular internalization and uptake by cellular nuclei. Compared to the parent CD-TAEA, PB-AD/CD- TAEA assemblies mediated higher transfection rates, which were even comparable to that of PEI25K. In addition, PB-AD/CD- TAEA displayed much lower cytotoxicity than PEI25K in both 293T and HeLa cell lines. The encouraging results suggest that CD-TAEA can be developed as a powerful template capable of readily accommodating various AD-based modules giving versatile functionalities for improved transfection.
YANG BinLV YinWANG QingRongLIU YunAN HongFENG JunZHANG XianZhengZHUO RenXi
A novel Uralic(U)-rich linear-hyperbranched mono-methoxy poly(ethylene glycol)-hyperbranched polyglycerol-graft-Uralic(mPEG-HPG-g-U)nanoparticle(NP)was prepared as drug carrier for antitumor methotrexate(MTX).Due to the H-bond interaction of U with MTX and hydrophobic interaction,this NP exhibited high drug loading efficiency of up to 40%,which was significantly higher than that of traditional NPs based on U-absent copolymers(<15%).In addition,MTX-loaded mPEG-HPG-g-U NPs also demonstrated an acidity-accelerated drug release behavior.
