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:9260776
- 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
- 来源:
- 关键词:Acute Myelocytic LeukemiaAlpha CellAutologous Stem Cell TransplantationBackBindingBiodistributionBiological ModelsBloodBlood CirculationBlood VesselsBone MarrowC-Type LectinsCell Differentiation processCell LineCell Surface ProteinsCell surfaceCellsClinicalCollectionCytotoxic agentDaunorubicinDiseaseDisulfidesDoseDrug Delivery SystemsDrug FormulationsDrug resistanceEnvironmentFeedbackFormulationGoalsHematopoietic stem cellsHigh Dose ChemotherapyInpatientsLeukemic CellLigandsMaximum Tolerated DoseMicellesMinorityMonitorMusNatural regenerationPatientsPeptidesPharmaceutical PreparationsPhysiologicalPlant RootsPlasmaPolymersPopulationRecurrenceRegimenResistanceSamplingSolid NeoplasmSpecific qualifier valueSpecimenStem cellsSupportive careSurfaceTestingTimeToxic effectTreatment outcomeXenograft procedureamphiphilicityaqueousbasechemotherapycrosslinkdensitydisulfide bondimprovedin vivointravenous administrationkillingsleukemialeukemic stem cellmortalitynanoparticlenanoscalenanotherapeuticneoplastic cellpreclinical studypublic health relevancepurgeresistance mechanismsystemic toxicitytargeted deliverytargeted treatmenttumor
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.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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CHONG-XIAN PAN其他文献
CHONG-XIAN PAN的其他文献
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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:
9454297 - 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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