Yanhua Zhang,Hui Huang,Hao Fu,Meng Zhao,Zhihua Wu,Yang Dong,He Li,Yourong Duan,Ying Sun
As known to all, ovarian cancer ranks the most lethal of the gynecological malignancies. The antitumor drugs based on platinum are first-line chemotherapy drugs for ovarian cancer. However, their therapeutic efficiency is severely limited owing to dose-limiting toxicities of platinum. New theranostic strategies to overcome chemotherapy toxicity is highly desirable. Meanwhile, the real-time treating effect is not visible for doctors. Herein, we constructed PFH/siRNA/Fe3O4@Pt(IV) NPs-cRGD (NPs-cRGD) for precise theranostics against ovarian tumors with real-time imaging. The NPs-cRGD had a good storage stability and resisted the serum-induced aggregation, which was beneficial for drug delivery. Additionally, gel-retardation assay demonstrated that the NPs-cRGD exhibited great protection to siRNA to resist nuclease degradation. In vitro, the NPs-cRGD showed good dual-mode US/MRI imaging and the relative imaging research was also discussed. Moreover, the in vitro experiments indicated that the NPs-cRGD with US exhibited excellent antitumor therapeutic efficiency, resulting from the cRGD ligands and US exposure enhanced the cellular uptake efficiency. Thus, the dual-mode nanoparticles in this work may provide precious insight into the development of various multi-mode nanoplatforms delivering drugs or genes for precise theranostics against various cancer.
Shen-Fei Wang,Xin Liu,Mo-Yu Ding,Shuangcheng Ma,Jing Zhao,Ying Wang,Shaoping Li
Reducing agents are crucial for the management of maladaptive inflammation-induced macrophage death and hematopoietic toxicity of chemotherapy. 2- O - β - d -glucopyranosyl- l -ascorbic acid (AA-2 β G), a unique AA (or vitamin C) derivative identified in Lycium barbarum , exhibited enhanced free radical scavenging activity compared with AA and its synthetic derivative AA-2 α G. AA-2 β G protected hydrogen peroxide-induced cell death in murine macrophage RAW264.7 cells. Treatment with AA-2 β G eliminated oxidative stress and the ratio of cellular glutathione to glutathione disulfide more effectively than AA and AA-2 α G. AA-2 β G also significantly reduced the fluorescent intensity of DCFH-DA triggered by chemotherapeutic agent camptotehcin-11 but not fluorouracil. AA, AA-2 α G, and AA-2 β G significantly decreased Keap-1expression, and increased the expression levels of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1. All compounds triggered the nuclear translocation of Nrf2, while the ability of AA-2 β G to enhance the Nrf2-DNA binding affinity was approximately two fold as those of AA and AA-2 α G. Sodium ascorbate cotransporters (SVCT) inhibitors, sulfinpyrazone, phloretin, and 3- O -methyglucose, potently abrogated the free radical scavenging activities of AA, AA-2 α G, and AA-2 β G. The cellular uptake efficacy of AA-2 α G and AA-2 β G was less than 10% of AA, while the inhibition of SVCT with sulfinpyrazone considerably diminished the uptake efficacy of these compounds. AA-2 α G and AA-2 β G are more stable in the Fenton reagents than AA. In summary, AA-2 β G from L. barbarum with excellent free radical scavenging activity is a promising natural AA derivative for further pharmacological evaluation.
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