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  • Title: Suppression of VEGF by reversible-PEGylated histidylated polylysine in cancer therapy.
    Author: Cai X, Zhu H, Dong H, Li Y, Su J, Shi D.
    Journal: Adv Healthc Mater; 2014 Nov; 3(11):1818-27. PubMed ID: 24805287.
    Abstract:
    A reversible-PEGylated polylysine is designed and developed for efficient delivery of siRNA. In this unique structure, the ε-amino groups of disulfide linked poly(ethylene glycol) (PEG) and polylysine (mPEG-SS-PLL) are partially replaced by histidine groups, in order to develop the histidylated reversible-PEGylated polylysine (mPEG-SS-PLH), for enhanced endosome escape ability. The transfection efficacy of mPEG-SS-PLH is found to closely correlate with histidine substitution. Its maximum transfection efficiencies are determined, respectively, to be 75%, 42%, and 24%, against 293T, MCF-7, and PC-3 cells. These data indicate that the transfection efficiencies can equal or even outweigh PEI-25k in the corresponding cells (80%, 38.5%, and 20%). The in vivo circulation and biodistribution of the polyplexes are monitored by fluorescent imaging. The in vivo gene transfection is carried out by intravenous injection of pEGFP to BALB/c mice using the xenograft models. The in vivo experimental results show effective inhibition of tumor growth by mPEG-SS-PLH/siRNA-VEGF, indicating its high potential for clinical applications.
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