Referencia completa del registroAccession Number: | 00078447-201712280-00010.
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Author: | Wu, Xiaoyan a,b,1; Hu, Zhenhua a,1; Nizzero, Sara a; Zhang, Guodong a; Ramirez, Maricela R. a; Shi, Ce c; Zhou, Jin c; Ferrari, Mauro a,d; Shen, Haifa a,e,*
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Institution: | (a) Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA (b) Department of Pediatric Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China (c) Department of Hematology, First Affiliated Hospital, Harbin Medical University, Harbin 150081, China (d) Department of Medicine, Weill Cornell Medical College, New York, NY, USA (e) Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA
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Title: | Bone-targeting nanoparticle to co-deliver decitabine and arsenic trioxide for effective therapy of myelodysplastic syndrome with low systemic toxicity.[Article]
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Source: | Journal of Controlled Release. 268:92-101, December 28, 2017.
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Abstract: | : Myelodysplastic syndromes (MDS) are a diverse group of bone marrow disorders and clonal hematopoietic stem cell disorders characterized by abnormal blood cells, or reduced peripheral blood cell count. Recent clinical studies on combination therapy of decitabine (DAC) and arsenic trioxide (ATO) have demonstrated synergy on MDS treatment, but the treatment can cause significant side effects to patients. In addition, both drugs have to be administered on a daily basis due to their short half-lives. In addressing key issues of reducing toxic side effects and improving pharmacokinetic profiles of the therapeutic agents, we have developed a new formulation by co-packaging DAC and ATO into alendronate-conjugated bone-targeting nanoparticles (BTNPs). Our pharmacokinetic studies revealed that intravenously administered BTNPs increased circulation time up to 3 days. Biodistribution analysis showed that the BTNP facilitated DAC and ATO accumulation in the bone, which is 6.7 and 7.9 times more than untargeted NP. Finally, MDS mouse model treated with BTNPs showed better restoration of complete blood count to normal level, and significantly longer median survival as compared to free drugs or untargeted NPs treatment. Our results support bone-targeted co-delivery of DAC and ATO for effective treatment of MDS.
(C) 2017Elsevier, Inc.
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Author Keywords: | Myelodysplastic syndrome; Bone marrow; Delivery; Nanoparticle; Decitabine; Arsenic trioxide.
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Language: | English.
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Document Type: | Research papers.
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Journal Subset: | Pharmacology.
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ISSN: | 0168-3659
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DOI Number: | https://dx.doi.org/10.1016/j.jco...- se abre en una ventana nueva
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