【摘 要】
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Combined delivery of drug and gene has emerged as an exciting method of treating cancer which possesses a synergistic effect of increasing drug efficacy or enhancing gene transfection efficiency, ther
【机 构】
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School of Pharmaceutical Science, Shandong University, 44 Wenhuaxi Road, Jinan,Shandong Province 250
【出 处】
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第二届全国生物颗粒学术研讨会、第三届国际工业药学和临床药学研讨会暨第一届岭南国际药学大会
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Combined delivery of drug and gene has emerged as an exciting method of treating cancer which possesses a synergistic effect of increasing drug efficacy or enhancing gene transfection efficiency, thereby increasing the efficiency of cancer treatment and prolong the survival time of cancer patients.However, endow the co-delivery systems with efficient intracellular (tumor cell) delivery and tumor sensitive drug release remains a big challenge.In this study, the multifunctional nanocarrier PDT with tumor cell internalization enhancement and pH-sensitive drug release was designed and prepared for the co-delivery of doxorubicin (DOX) and tumor necrosis factor-related apoptosis-inducing ligand encoding plasmid gene (pTRAIL).Firstly, Poly(ethyleneimine) (PEI)-polyethylene glycol (PEG)-cell penetrating peptide (TAT) conjugates (PEI-PEG-TAT, PPT, enhance cellular internalization)and DOX-PEI (DP, linked with hydrazone bonds, pH-sensitive drug release) were successfully synthesized and the molecular structure was characterized by 1H NMR.Then,PPT and DP were mixed and used to condense pTRAIL (N/P ratio=100∶64) to form the DOX and pTRAIL co-loaded PPT/DP/pTRAIL nanocarriers (PDT).PDT exhibited spherical structures with the particle size distribution of 80.29±3.66 nm.The cellular uptake of PDT was evaluated on HepG2 and SKOV3 cells and the results showed that 30% PPT contents in PDT could significantly increase the cell uptake rates compared to the nanocarriers without PPT contents.The MTT assay results showed that PDT could significantly enhance the anti-tumor efficiency both in HepG2 and SKOV3 cells at the DOX concentration of 0.05~10μg/mL compared to free DOX and PCT (only loaded with pTRAIL).Westem Blot assay results showed that the PDT could significantly enhance the pTRAIL protein expression after transfection compared with free pTRAIL.There results demonstrated that PDT could enhancement of DOX and pTRAIL tumor cell internalization and intracellular DOX release,which indicated that PDT hold great potential as a drug and gene co-delivery carriers to improve the combination antitumor effects.
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