Drug-Loaded Nanobubbles for Ultrasound Enhanced Delivery to Colon Cancer Liver Metastasis
用于超声增强递送至结肠癌肝转移的载药纳米气泡
基本信息
- 批准号:10696225
- 负责人:
- 金额:$ 46.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-30 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdvanced Malignant NeoplasmAntineoplastic AgentsAreaBiodistributionBlood CellsBlood VesselsBreastCell Culture TechniquesCell WallCell modelCellsChemotherapy-Oncologic ProcedureClinicClinicalColonColon CarcinomaColorectal CancerComplexContrast MediaDataDedicationsDiagnosisDiameterDiseaseDoseDose LimitingDrug CarriersDrug Delivery SystemsDrug KineticsDrug TransportEffectivenessEngineeringEquipmentEsophagusExcisionExtravasationFormulationFrequenciesGasesGoalsHCT116 CellsHumanHybridsImageIn VitroInjectionsIntestinesIntravenousKidneyLS174T colon cancer cell lineLarge Intestine CarcinomaLipidsLiposomesLiverLungMeasuresMediatingMetastatic Neoplasm to the LiverMicellesMicrobubblesModelingMusNanotechnologyOralOrganOutcomeOutcomes ResearchPancreasPatientsPenetrationPerformancePermeabilityPharmaceutical PreparationsPhysiologic pulsePlayPolymersPredispositionResearchResearch SupportRoleSignal TransductionSiteSolid NeoplasmStomachSystemTechniquesTechnologyTestingTherapeuticTherapeutic AgentsTimeTissuesToxic effectTransducersTranslatingTreatment EfficacyTreatment outcomeTumor TissueTumor VolumeUnited StatesVascular blood supplyVisualizationWorkcancer cellcancer diagnosiscell killingchemosensitizing agentchemotherapeutic agentchemotherapyclinical imagingclinically relevantcolon cancer patientscolorectal cancer metastasisdelivery vehicledesigndrug distributiondrug efficacyeffective therapyimage-guided drug deliveryimaging propertiesimprovedin vivointerestmelanomametastatic colorectalmeternanobubblenanoparticleneoplastic cellparticleresponsescale upself assemblysuccesssystemic toxicitytheranosticstime usetreatment strategytumortumor growthtumor heterogeneitytumor microenvironmentultrasounduptake
项目摘要
PROJECT SUMMARY
Drug-Loaded Nanobubbles for Ultrasound Enhanced Delivery to Colon Cancer Liver Metastasis
Most advanced cancers can spread to the liver including those of the breast, esophagus, stomach, pancreas,
colon, lungs, kidneys and even melanoma. Liver metastases (also referred to as secondary liver cancer) cannot
be cured in the majority of cases, and most patients presenting with liver metastases will die of the disease. The
problem is most pronounced in colorectal cancer, where nearly 85% of the 150,000 patients diagnosed in the
United States each year will eventually develop metastatic disease in the liver due to the shared blood supply
between the intestine and the liver. Effective treatment options at this stage are severely limited, and most cases
are treated with oral or intravenous chemotherapy. The median survival for patients receiving systemic
chemotherapy is still only 21 months due primarily to low drug uptake in the tumor, serious systemic toxicity and
heterogeneous drug distribution at tumor sites. To meet the urgent need for more effective treatment options for
liver metastases, we plan to develop a hybrid theranostic nanobubble which is inherently ultrasound
visible and ultrasound-deployable on demand in real time at the region of interest. Our exciting preliminary
data demonstrate that even after a single application of ultrasound immediately following particle injection,
ultrasound-triggered delivery leads to significantly higher drug concentration in tumors and results in more
homogeneous distribution within tumor compared to free drug and non-triggered particles. This suggests that,
especially after parameters are optimized, treatment of tumors with the proposed construct has the potential to
maximize drug dose at the tumor site and should lead to improved survival. Within the scope of this project we
thus propose to optimize formulation and treatment parameters essential to the success of this approach. Some
aspects that distinguish our technology from others include 1) nanoparticles used in the study are 100-300 nm
in diameter and yet have strong ultrasound response making them visible at clinically relevant frequencies of 3-
12 MHz; 2) nanoparticles have augmented cargo capacity to enable simple and efficient drug loading directly
into the particle; 3) payload release can be triggered with the imaging transducer using standard pulse sequences
already available on clinical scanners; 4) nanoparticle is self-assembled and thus easily formulated and scaled
up. The project will be carried out in four aims with Aims 1 and 2 being dedicated to in vitro characterization and
optimization of the construct and Aims 3 and 4 evaluating in vivo performance. The ultimate goal of this work
is to develop and optimize an image-guided drug delivery strategy that will maximize drug accumulation
in tumors and lead to augmented, homogeneous drug distribution within the tumor volume while
minimizing systemic accumulation compared to free drug. The outcome of this research will be a more
effective strategy to improve delivery of chemotherapeutic agents to metastatic liver tumors.
Impact: We are confident that the advantages and unique aspects of our nanoparticles will enable successful
completion of this objective. These nanoparticles will overcome the drug transport challenges and will improve
the effectiveness of chemotherapy regimens used in treating secondary liver cancer with ultimate goal to
translate this research to the clinic.
项目总结
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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{{ truncateString('Agata A Exner', 18)}}的其他基金
Development of a novel imaging modality for adoptive cell therapy
开发用于过继细胞治疗的新型成像方式
- 批准号:
10316427 - 财政年份:2021
- 资助金额:
$ 46.31万 - 项目类别:
Drug-Loaded Nanobubbles for Ultrasound Enhanced Delivery to Colon Cancer Liver Metastasis
用于超声增强递送至结肠癌肝转移的载药纳米气泡
- 批准号:
10019356 - 财政年份:2019
- 资助金额:
$ 46.31万 - 项目类别:
Drug-Loaded Nanobubbles for Ultrasound Enhanced Delivery to Colon Cancer Liver Metastasis
用于超声增强递送至结肠癌肝转移的载药纳米气泡
- 批准号:
9764722 - 财政年份:2019
- 资助金额:
$ 46.31万 - 项目类别:
Drug-Loaded Nanobubbles for Ultrasound Enhanced Delivery to Colon Cancer Liver Metastasis
用于超声增强递送至结肠癌肝转移的载药纳米气泡
- 批准号:
10181954 - 财政年份:2019
- 资助金额:
$ 46.31万 - 项目类别:
Pressure-Driven Local Drug Delivery System for Treatment of Liver Cancer
用于治疗肝癌的压力驱动局部给药系统
- 批准号:
8843429 - 财政年份:2013
- 资助金额:
$ 46.31万 - 项目类别:
Pressure-Driven Local Drug Delivery System for Treatment of Liver Cancer
用于治疗肝癌的压力驱动局部给药系统
- 批准号:
8504165 - 财政年份:2013
- 资助金额:
$ 46.31万 - 项目类别:
Pressure-Driven Local Drug Delivery System for Treatment of Liver Cancer
用于治疗肝癌的压力驱动局部给药系统
- 批准号:
9062872 - 财政年份:2013
- 资助金额:
$ 46.31万 - 项目类别:
Pressure-Driven Local Drug Delivery System for Treatment of Liver Cancer
用于治疗肝癌的压力驱动局部给药系统
- 批准号:
8653570 - 财政年份:2013
- 资助金额:
$ 46.31万 - 项目类别:
Vascular Modulation for Enhancement of Image-Guided RF Ablation
用于增强图像引导射频消融的血管调制
- 批准号:
7781804 - 财政年份:2010
- 资助金额:
$ 46.31万 - 项目类别:
Vascular Modulation for Enhancement of Image-Guided RF Ablation
用于增强图像引导射频消融的血管调制
- 批准号:
8027740 - 财政年份:2010
- 资助金额:
$ 46.31万 - 项目类别: