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• W2028479985 abstract "d-Penicillamine is an aminothiol that is cytotoxic to cancer cells and generates dose dependent reactive oxygen species (ROS) via copper catalyzed oxidation. However, the delivery of d-pen to cancer cells remains a challenge due to its high hydrophilicity, highly reactive thiol group and impermeability to the cell membrane. To overcome this challenge, we investigated a novel poly-l-glutamic acid (PGA) conjugate of d-pen (PGA−d-pen) where d-pen was conjugated to PGA modified with 2-(2-pyridyldithio)-ethylamine (PDE) via disulfide bonds. Confocal microscopy and cell uptake studies showed that the fluorescently labeled PGA−d-pen was taken up by human leukemia cells (HL-60) in a time dependent manner. Treatment of HL-60, murine leukemia cells (P388) and human breast cancer cells (MDA-MB-468) with PGA−d-pen resulted in dose dependent cytotoxicity and elevation of intracellular ROS levels. PGA−d-pen induced apoptosis in HL-60 cells which was verified by Annexin V binding. The in vivo evaluation of the conjugate in the P388 murine leukemia model (intraperitoneal) resulted in significant enhancement in the survival of CD2F1 mice over vehicle control." @default.
• W2028479985 created "2016-06-24" @default.
• W2028479985 creator A5026506971 @default.
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• W2028479985 date "2010-04-06" @default.
• W2028479985 modified "2023-10-16" @default.
• W2028479985 title "Intracellular Delivery of the Reactive Oxygen Species Generating Agent <scp>d</scp>-Penicillamine upon Conjugation to Poly-<scp>l</scp>-glutamic Acid" @default.
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• W2028479985 doi "https://doi.org/10.1021/mp1000058" @default.
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