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
- 来源:
- 关键词:Acute Myelocytic LeukemiaAutologous Stem Cell TransplantationBackBindingBiodistributionBiological ModelsBloodBlood CirculationBlood VesselsBone MarrowC-Type LectinsCell 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 administrationleukemialeukemic stem cellmortalitynanoparticlenanoscalenanotherapeuticneoplastic cellpreclinical studypublic health relevancepurgeresistance mechanismstem cell differentiationsystemic 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.
描述(申请人提供):该项目的目标是开发纳米疗法,能够将化疗药物柔红霉素特异性地输送到急性髓系白血病(AML)干细胞中(靶向输送),并在细胞内释放药物(定时释放),以根除这一细胞群。目前对AML的化疗令人失望,因为它只能治愈一小部分AML患者,而且即使在加强住院监测和支持性护理的情况下,也存在严重的毒性和显著的死亡率。白血病干细胞(LSC)对常规化疗具有相对耐受性,可以产生更多的白血病细胞,从而导致疾病复发。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上特异表达,而在正常造血干细胞上不表达。我们已经开发出一种针对CLL1的多肽。当这种多肽共价连接到纳米级胶束药物配方上时,产生的靶向纳米颗粒称为胶束,可以将药物负载特异性地输送到表达CLL1的细胞中,包括临床白血病标本。这种载药、CLL1靶向的胶束在血液中稳定,可通过以下方式潜在地改善AML的治疗:(1)将高局部浓度的柔红霉素特异性地输送到LSC中,压倒耐药机制并根除LSC;(2)通过从胶束中释放柔红霉素并使LSC进入循环,杀死全身的白血病细胞;(3)减少因药物在胶束内的隔离而导致的治疗毒性和死亡率;以及(4)通过将柔红霉素制成胶束,允许在降低毒性的情况下给予高剂量柔红霉素。
项目成果
期刊论文数量(0)
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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
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A Phase I trial of cancer-targeting micelles for non-myoinvasive bladder cancer
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10426035 - 财政年份:2020
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$ 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
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10578717 - 财政年份:2020
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Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer
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10158416 - 财政年份:2018
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$ 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
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$ 35.91万 - 项目类别:
Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer
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10085104 - 财政年份:2018
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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:
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Development of targeting nanotherapeutics against bladder cancer
膀胱癌靶向纳米疗法的开发
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膀胱癌靶向纳米疗法的开发
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- 资助金额:
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