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.
家长资助奖摘要
项目摘要:三阴性乳腺癌(TNBC)约占浸润性乳腺癌的15%
癌症与侵袭性肿瘤生物学、预后不良、耐药、内脏转移和
早期疾病复发。TNBC在年轻女性中比在老年女性和非洲人中更常见-
美国和西班牙裔妇女。与非铂类药物相比,铂类药物对TNBC的敏感性更高。
最近,铂类药物在TNBC中的治疗重新引起了人们的兴趣,尤其是
卡铂联合紫杉醇(PTX)。Sacituzumab gov.itecan是由一种抗trop-2抗体组成的
与化疗药物(SN-38)有关,FDA批准了接受过TNBC治疗的患者
之前至少接受过两次化疗。FDA批准了这种免疫疗法药物的加速批准
阿替唑单抗联合化疗(NaB-紫杉醇)治疗TNBC(肿瘤阳性)
对于PD-L1)。因此,化疗在TNBC的治疗管理中是重要的,即使在出现的时候
免疫治疗和靶向治疗。然而,众所周知,化疗会导致致命的外周血管疾病。
神经病除了反应差、转移、复发和发展多药耐药外。这个
这一应用的目标是开发多功能靶向纳米颗粒,能够实现更好的
对TNBC患者的结果:(A)有针对性地将大剂量多种药物输送到癌细胞中(每次
生物识别事件与单一免疫靶向药物(例如,saituzumab goitecan-hziy)相比),以最大限度地提高
治疗效果,同时降低全身毒性(脱靶毒性);(B)EGFR受体靶向纳米粒
促进细胞内药物传递和释放,并可绕过多药耐药蛋白(p-
糖蛋白)介导药物分子外流;(C)能够长循环而不被隔离
进入肝脏。EGFR被TNBC过度表达,文献中充斥着使用西妥昔单抗的例子
通过靶向EFGR进行治疗。我们假设可生物降解聚合物的发展
纳米技术平台,核心含有卡铂和紫杉醇,使用西妥昔单抗(标记在
纳米颗粒表面)作为靶向部分将改善TNBC患者的预后,不同于重复
化疗周期中使用大剂量的细胞毒药物。我们假设双负荷多功能
靶向纳米粒在体外具有活性,在小鼠TNBC异种移植模型中显示出体内疗效
阳性肿瘤。目的1:制备载聚合物染料和紫杉醇、卡铂的隐身材料
可水解性交联西妥昔单抗表面靶向聚乳酸(PLL)纳米粒。目标2:角色塑造
含卡铂和紫杉醇的抗EGFR单抗(西妥昔单抗)表面靶向PLL纳米粒在小鼠体内的研究
核心。目的#3:荷瘤小鼠体内的生物分布和疗效研究。这项工作将带来
化疗药物、分子靶向治疗和纳米技术的结合力量
EGFR阳性对TNBC耐药,并以最小的毒性提高疗效。
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:
9265808 - 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:
8793606 - 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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