Administrative Supplements for Equipment Purchases for Select NIGMS_Akala
特定 NIGMS_Akala 设备采购的行政补充
基本信息
- 批准号:10793724
- 负责人:
- 金额:$ 9.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:ABCB1 geneAccelerationAdministrative SupplementAfrican AmericanAntibodiesApplications GrantsAwardBiodistributionBrainBreast Cancer PatientBreast Cancer TreatmentBypassCarboplatinCetuximabCirculationCodeCytotoxic agentDevelopmentDoseDrug Delivery SystemsDrug EffluxDyesEpidermal Growth Factor ReceptorEquipmentEventFluorescent DyesGiftsGoalsGrantHispanicImmunotherapyIn VitroInterruptionLinkLiteratureLiverMediatingMonoclonal AntibodiesMulti-Drug ResistanceMusNanotechnologyNational Institute of General Medical SciencesNeoplasm MetastasisOutcomePaclitaxelPatient-Focused OutcomesPeripheral Nervous System DiseasesPharmaceutical PreparationsPlatinumPolymersPositioning AttributePostdoctoral FellowPrior ChemotherapyPrognosisRecurrent diseaseRelapseResearch SupportResistanceSN-38SurfaceSystemTechnologyTherapeuticTherapeutic EffectTissuesToxic effectTumor BiologyVisceral metastasisWomanWorkXenograft Modelbiodegradable polymercancer cellchemotherapeutic agentchemotherapycrosslinkdiscountefficacy studyequipment acquisitionfabricationimprovedin vivointerestmalignant breast neoplasmmolecular targeted therapiesnanoparticlenanotechnology platformolder womenoverexpressionparent grantpoly(lactide)programmed cell death ligand 1programsreceptorresponsestudent trainingsystemic toxicitytargeted deliverytargeted treatmenttriple-negative invasive breast carcinomatumoryoung woman
项目摘要
Abstract of the Parent Grant Award
Project Summary: Triple-negative breast cancer (TNBC) accounts for approximately 15% of invasive breast
cancers and is associated with aggressive tumor biology, poor prognosis, resistance, visceral metastases and
earlier disease recurrence. TNBC is more common in younger women than in older women and in African-
American and Hispanic women. Platinum-based drugs showed higher sensitivity in TNBC compared to non-
TNBC patients and recently there has been a renewed interest for platinum therapy in TNBC, especially
combination of carboplatin with paclitaxel (PTX). Sacituzumab govitecan is made up of an anti–Trop-2 antibody
linked to the chemotherapy drug (SN-38) and was cleared by the FDA for TNBC patients who have undergone
at least two prior chemotherapies. The FDA granted an accelerated approval for the immunotherapy drug
atezolizumab in combination with chemotherapy (nab-paclitaxel) for the treatment of TNBC (for tumors positive
for PD-L1). Thus chemotherapy is important in the therapeutic management of TNBC even in the advent
of immunotherapy and targeted therapy. However, chemotherapies are known to cause fatal peripheral
neuropathy in addition to poor response, metastasis, relapse and development of multidrug resistance. The
goal of this application is the development of multifunctional targeted nanoparticles capable of achieving better
outcomes for TNBC patients: (a) targeted delivery of large doses of multiple drugs into cancer cells (per a single
biorecognition event compared to a single immunotargeted drug (e.g. sacituzumab govitecan-hziy)) to maximize
therapeutic effects while reducing systemic toxicity (off target toxicity); (b) EGFR-receptor targeted nanoparticles
that promote intracellular drug delivery and release and which can bypass multidrug resistant protein (p-
glycoprotein) which mediates efflux of drug molecules; (c) capable of long circulation without being sequestered
into the liver. EGFR is overexpressed by TNBC and literature is replete with examples of the use of cetuximab
in therapy by targeting EFGR. We hypothesize that the development of biodegradable polymeric
nanotechnology platform containing carboplatin and paclitaxel in the core and using cetuximab (tagged on
nanoparticle surface) as a targeting moiety will improve TNBC patients’ outcomes, unlike repeated
chemotherapy cycles with high doses of cytotoxic drugs. We hypothesize that the dual-loaded multifunctional
targeted nanoparticles will be active in vitro and show in vivo efficacy in mouse xenograft models of TNBC
positive tumors. Aim #1: Fabrication of polymeric dye-loaded and-paclitaxel and carboplatin-loaded stealth
hydrolysable crosslinked cetuximab surface-targeted polylactide (PLL) nanoparticles. Aim #2: Characterization
of anti-EGFR mAb (cetuximab) surface-targeted-PLL-nanoparticles containing carboplatin and paclitaxel in the
core. Aim #3: Biodistribution and efficacy studies in tumor-bearing mice. This work will bring to bear the
combined power of chemotherapeutic agents, molecular targeted therapy and nanotechnology to overcome
EGFR positive TNBC resistance and improve efficacy with minimal toxicity.
家长助学金摘要
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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EMMANUEL O AKALA其他文献
EMMANUEL O AKALA的其他文献
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{{ truncateString('EMMANUEL O AKALA', 18)}}的其他基金
Multifunctional Nanotechnology Platform for Triple Negative Breast Cancer Treatment
用于三阴性乳腺癌治疗的多功能纳米技术平台
- 批准号:
10411148 - 财政年份:2022
- 资助金额:
$ 9.65万 - 项目类别:
Multifunctional Nanotechnology Platform for Triple Negative Breast Cancer Treatment
用于三阴性乳腺癌治疗的多功能纳米技术平台
- 批准号:
10672232 - 财政年份:2022
- 资助金额:
$ 9.65万 - 项目类别:
Novel Nanotechnology Platform for Breast Cancer Treatment
用于乳腺癌治疗的新型纳米技术平台
- 批准号:
8793606 - 财政年份:2015
- 资助金额:
$ 9.65万 - 项目类别:
Novel Nanotechnology Platform for Breast Cancer Treatment
用于乳腺癌治疗的新型纳米技术平台
- 批准号:
9265808 - 财政年份:2015
- 资助金额:
$ 9.65万 - 项目类别:
Biodegradable Polymeric Nanosphere Drug Delivery System For Cancer Chemotherapy
用于癌症化疗的可生物降解聚合物纳米球药物输送系统
- 批准号:
7648081 - 财政年份:2008
- 资助金额:
$ 9.65万 - 项目类别:
Biodegradable Polymeric Nanosphere Drug Delivery System For Cancer Chemotherapy
用于癌症化疗的可生物降解聚合物纳米球药物输送系统
- 批准号:
7898892 - 财政年份:2008
- 资助金额:
$ 9.65万 - 项目类别:
Biodegradable Polymeric Nanosphere Drug Delivery System For Cancer Chemotherapy
用于癌症化疗的可生物降解聚合物纳米球药物输送系统
- 批准号:
7341850 - 财政年份:2008
- 资助金额:
$ 9.65万 - 项目类别:
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