Targeted- and timed-releasing nanotherapeutics against leukemia stem cells

针对白血病干细胞的靶向和定时释放纳米疗法

基本信息

  • 批准号:
    9454297
  • 负责人:
  • 金额:
    $ 35.91万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-04-15 至 2020-03-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): The goal of this project is to develop nanotherapeutics that can specifically deliver the chemotherapeutic drug daunorubicin into acute myeloid leukemia (AML) stem cells (targeted delivery) and release the drug inside the cells (timed release) in order to eradicate this cell population. Current chemotherapy for AML is disappointing in that it can cure only a minority of AML patients and is associated with severe toxicity and significant mortality even with intensive inpatient monitoring and supportive care. Leukemia stem cells (LSC) are relatively resistant to the conventional chemotherapy and can subsequently produce more leukemia cells to cause disease recurrence. In order to cure leukemia, LSC must be eradicated. The C-type lectin-like molecule-1 (CLL-1) is a cell surface protein that is specifically expressed on most AML LSC, but not on normal hematopoietic stem cells. We have developed a peptide that specifically targets CLL1. When this peptide is covalently attached to a nanometer-scale micellar drug formulation, the resulted targeting nanoparticles, called micelles, can specifically deliver the drug load into cells expressing CLL1, including clinical leukemia specimens. The drug-loaded, CLL1-targeting micelles are stable in blood, and can potentially improve therapy against AML by (1) delivering a high local concentration of daunorubicin specifically into LSC, overwhelming the resistant mechanisms and eradicating LSC; (2) killing leukemic cells throughout the body with the release of daunorubicin from the micelles and LSC into circulation; (3) decreasing therapy-induced toxicity and mortality owing to the sequestration of the drug inside the micelles; and (4) allowing administration of high-dose daunorubicin with reduced toxicity through formulation of daunorubicin into micelles.
 描述(由申请人提供):该项目的目标是开发纳米治疗剂,其可以特异性地将化疗药物柔红霉素递送到急性髓性白血病(AML)干细胞中(靶向递送),并在细胞内释放药物(定时释放),以根除该细胞群。目前AML的化疗令人失望,因为它只能治愈少数AML患者,即使在强化住院监测和支持性护理下,也与严重毒性和显著死亡率相关。白血病干细胞(Leukemia stem cells,LSC)对常规化疗具有较强的抵抗力,可产生更多的白血病细胞,导致疾病复发。为了治愈白血病,必须根除LSC。C型凝集素样分子-1(CLL-1)是一种细胞表面蛋白,在大多数AML LSC上特异性表达,但在正常造血干细胞上不表达。我们开发了一种特异性靶向CLL 1的肽。当这种肽共价连接到纳米级胶束药物制剂时,所产生的靶向纳米颗粒(称为胶束)可以特异性地将药物负载递送到表达CLL 1的细胞中,包括临床白血病标本。载药的CLL 1靶向胶束在血液中是稳定的,并且可以通过(1)将高局部浓度的柔红霉素特异性递送到LSC中,压倒耐药机制并根除LSC;(2)通过柔红霉素从胶束和LSC释放到循环中杀死全身的白血病细胞;(3)由于药物在胶束内的隔离,降低了治疗诱导的毒性和死亡率;和(4)通过将柔红霉素配制成胶束,允许以降低的毒性施用高剂量柔红霉素。

项目成果

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CHONG-XIAN PAN其他文献

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{{ truncateString('CHONG-XIAN PAN', 18)}}的其他基金

BCCMA: Translational research to improve the care of advanced bladder cancer
BCCMA:改善晚期膀胱癌护理的转化研究
  • 批准号:
    10588312
  • 财政年份:
    2023
  • 资助金额:
    $ 35.91万
  • 项目类别:
A Phase I trial of cancer-targeting micelles for non-myoinvasive bladder cancer
癌症靶向胶束治疗非肌浸润性膀胱癌的 I 期试验
  • 批准号:
    10426035
  • 财政年份:
    2020
  • 资助金额:
    $ 35.91万
  • 项目类别:
A Phase I trial of cancer-targeting micelles for non-myoinvasive bladder cancer
癌症靶向胶束治疗非肌浸润性膀胱癌的 I 期试验
  • 批准号:
    10578717
  • 财政年份:
    2020
  • 资助金额:
    $ 35.91万
  • 项目类别:
Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer
靶向纳米卟啉增强膀胱癌的免疫治疗
  • 批准号:
    10158416
  • 财政年份:
    2018
  • 资助金额:
    $ 35.91万
  • 项目类别:
Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer
靶向纳米卟啉增强膀胱癌的免疫治疗
  • 批准号:
    9898243
  • 财政年份:
    2018
  • 资助金额:
    $ 35.91万
  • 项目类别:
Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer
靶向纳米卟啉增强膀胱癌的免疫治疗
  • 批准号:
    10085104
  • 财政年份:
    2018
  • 资助金额:
    $ 35.91万
  • 项目类别:
Targeted-and timed-releasing nanotherapeutics against leukemia stem cells
针对白血病干细胞的靶向定时释放纳米疗法
  • 批准号:
    10162055
  • 财政年份:
    2015
  • 资助金额:
    $ 35.91万
  • 项目类别:
Targeted- and timed-releasing nanotherapeutics against leukemia stem cells
针对白血病干细胞的靶向和定时释放纳米疗法
  • 批准号:
    9260776
  • 财政年份:
    2015
  • 资助金额:
    $ 35.91万
  • 项目类别:
Development of targeting nanotherapeutics against bladder cancer
膀胱癌靶向纳米疗法的开发
  • 批准号:
    8442030
  • 财政年份:
    2013
  • 资助金额:
    $ 35.91万
  • 项目类别:
Development of targeting nanotherapeutics against bladder cancer
膀胱癌靶向纳米疗法的开发
  • 批准号:
    9275369
  • 财政年份:
    2013
  • 资助金额:
    $ 35.91万
  • 项目类别:

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自体干细胞移植后的 HIV 储库和基因修饰细胞动力学
  • 批准号:
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Systematic Light Exposure Effects on Circadian Rhythms Entrainment, Inflammation, Neutropenic Fever and Symptom Burden among Multiple Myeloma Patients undergoing Autologous Stem Cell Transplantation
系统性光照对接受自体干细胞移植的多发性骨髓瘤患者的昼夜节律拖累、炎症、中性粒细胞减少性发热和症状负担的影响
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