J Nanosci Nanotechnol
Department of Pediatrics, Central Hospital of Zibo, Zibo, 255036, Shandong Province, China.
Published: February 2021
As a first-line drug widely used in the treatment of leukemia, 6-MP has obvious effects on leukemia. However, 6-MP disadvantages such as poor solubility in water, easy binding with serum proteins, short circulation time, and large toxic and side effects greatly limit the application of 6-MP. For this reason, various 6-MP nano drug-loading systems have been designed to increase the water solubility of 6-MP, extend the circulation time, and increase the bioavailability of 6-MP to a certain extent, reducing its toxic and side effects. However, its therapeutic effect and is still far from expectations, and there is a lot of room for improvement. In order to solve the above problems encountered in the clinical application of 6-MP, we have tried two ways of polymer prodrugs and drug-loaded vesicles to achieve efficient targeted delivery and treatment of 6-MP. We designed hyaluronic acid (HA)-based gluteal-skin-responsive 6-MP polymer prodrug (HA-GS-MP) for highly effective targeted therapy of acute myeloid leukemia. Hyaluronic acid is a natural polysaccharide, which has excellent biocompatibility and biodegradability, and has a good ability to actively target malignant tumor cells overexpressing the CD receptor. 6-MP is connected to the HA chain through a vinyl sulfide bond, which is stable under physiological conditions (no drug release), and under intracellular reducing conditions, the connection bond is broken and 6-MP is quickly released. HA-GS-MP has a simple preparation process, good water solubility, long cycle time, and strong targeting ability. This GSH-responsive CD targeted 6-MP polymer prodrug is expected to improve the therapeutic effect on acute myeloid leukemia cells.
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http://dx.doi.org/10.1166/jnn.2021.18695 | DOI Listing |
BMC Bioinformatics
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Department of Applied Computer Science, University of Winnipeg, Winnipeg, MB, R3B 2E9, Canada.
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January 2025
Department of Pharmacology, University of Alberta, Edmonton, Canada. Electronic address:
Protein kinase C (PKC) signalling has been shown to be dysregulated in various cancers including acute lymphoblastic leukemia (ALL). We have previously determined that changes in the expression levels of SLC43A3-encoded equilibrative nucleobase transporter 1 (ENBT1) can significantly alter 6-mercaptopurine (6-MP) toxicity in ALL cells. 6-MP is a common drug used in ALL chemotherapy.
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Division of Hematology, Oncology, and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, USA.
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Department of Rheumatology, Shalamar Institute of Health Sciences, Lahore, Pakistan.
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View Article and Find Full Text PDFHaematologica
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