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.
Hydrogen peroxide(H2O2)detection in biological systems is of significant importance,which act as critical second messenger in fundamental biological processes.Here,we report on a chemoselective fluorescent naphthylimide peroxide probe(NPP)for the H_(2)O_(2)detection in vitro and in vivo.NPP is a phenylboronic acid-caged chromophore that selectively responds to H_(2)O_(2)through a selfimmolate mechanism.NPP exhibited high sensitivity and selectivity to H_(2)O_(2)with distinctive fluorescence change due to the excellent two-photon excitation property,which permits the facile detection of inflammation produced H_(2)O_(2)and offers chance to monitor the inflammatory stages in diseased cells.
Lei RongChi ZhangQi LeiMing-Ming HuJun FengHong-Bing ShuYi LiuXian-Zheng Zhang
A disulfide bond containing polypeptide, PolyK6-R8, was designed and prepared by oxidative polymerization between terminal cysteinyl thiol groups of CHK6HC and CR8C. The molar ratio between CHK6HC and CR8C within obtained PolyK6-Rs was 9：1, and PolyK6-R8 could combine DNA compactly when weight ratio reached 5. Through in vitro investigation, it was found that PolyK6-R8 was an efficient gene vector with low cytotoxicity for delivering DNA in both COS-7 and HeLa cells. Cellular uptake of DNA mediated by PolyK6-R8/DNA complexes was promoted after incubation for 4 h. Moreover, by examining the histological sections of hindlimb ischemia rats through immunohistochemistry, PolyK6- R8/VEGF complexes were proved to be effective in both VEGF protein expression and succeeding vessel formation. The results indicated that polypeptide-based PolyK6-R8 is a promising gene vector for the limb ischemia treatment.
Camptothecin(CPT)-based drugs always undergo the reversible,pH-dependent lactone ring-opening reaction,yielding the inactive but toxic carboxylate form.Self-assembly strategy provides an effective route for preserving their bio-stability.In this article,nano-sized self-assemblies from CPTbased antitumor drugs were simply built up by directly diluting the stock dimethylsulfoxide solutions of(S)-(t)-CPT,(S)-10-hydroxyl camptothecin and carboxylic CPT with water/phosphatebuffered saline solution.Because of their different molecular structures in A-ring or modification on the 20-OH group,CPT self-assembled into helical nano-ribbons,whereas 10-hydroxycamptothecin and carboxylic CPT self-aggregated into flat nano-ribbons and cylindric nano-rods,respectively.Attractively,the self-assembly of CPT-based drugs could occur within 1 min at a low concentration of 1×10^(-5)M.Adopting the J-type self-aggregation,self-assemblies were stable in aqueous solution and could effectively protect the CPT-based drugs from hydrolysis,which thereby kept their bioactivity for tumor therapy.
