Bionanotechnology approach for treatment of lung cancer
生物纳米技术治疗肺癌的方法
基本信息
- 批准号:10553243
- 负责人:
- 金额:$ 58.12万
- 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:2019-02-04 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AccountingAntineoplastic AgentsBiotechnologyBuffersCancer EtiologyCell Death InductionCell LineCell ProliferationCell SeparationCessation of lifeChargeColon CarcinomaDataDrug Delivery SystemsDrug KineticsDrug TargetingDrug resistanceDrug usageEngineeringEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor Tyrosine Kinase InhibitorExcisionGNRH1 geneGene ExpressionGenerationsGonadotropin-Releasing Hormone ReceptorHistologyHumanImmune responseImmunodeficient MouseIn VitroInduction of ApoptosisInhalationIntravenousInvadedLongevityLungMalignant NeoplasmsMalignant neoplasm of lungMalignant neoplasm of prostateMediatingMusMutationNanostructuresNanotechnologyNebulizerNeoplasm MetastasisNon-Small-Cell Lung CarcinomaNormal tissue morphologyOperative Surgical ProceduresOrganPaclitaxelPatientsPenetrationPersonsPharmaceutical PreparationsPostoperative PeriodPrimary NeoplasmProteinsReceptor Protein-Tyrosine KinasesReceptor SignalingResearchResistanceSerumShapesSignal InductionSignal PathwaySignal TransductionSmall Interfering RNASolubilitySpecificitySystemTechnologyTestingTherapeuticTherapeutic AgentsTreatment EffectivenessTreatment EfficacyTreatment Side EffectsTumor TissueTyrosine Kinase InhibitorUnited StatesXenograft procedurecancer cellcancer typechemotherapyclinically relevantcombination gene therapycombinatorialcytotoxicityestablished cell linegene therapygenotoxicityhuman modelimprovedin vivoinnovationlung Carcinomalung cancer cellmalignant breast neoplasmmolecular massmouse modelnanobiotechnologynanoparticlenanoscaleneoplastic cellnew therapeutic targetnoveloverexpressionparticlepeptide hormonepreventreceptorside effectsmall moleculestructured lipidsystemic toxicitytargeted deliverytargeted treatmenttreatment responsetumor
项目摘要
Project Title: Bio-nanotechnology approach for treatment of lung cancer
Project Summary
Lung cancer is the leading cause of cancer-related deaths worldwide. Non-Small Cell Lung Carcinoma
(NSCLC) is the most common type of lung cancer, accounting for more than 80% of all lung cancer cases.
Chemotherapy is the primary pre-operative and post-operative treatment of NSCLC. However, the efficiency of
chemotherapy remains relatively low in most patients and is limited by insufficient specificity, low drug
accumulation, and retention in the lungs with severe adverse side effects of treatment. Recently, small
molecule Tyrosine Kinase (TK) inhibitors which act on the Epidermal Growth Factor Receptors (EGFRs) were
introduced for treatment of NSCLC. However, even the latest generation of EGFR inhibitors cause severe
systemic toxicities and are ineffective in preventing non-canonical EGFR signaling. As a result, only
approximately 10% of patients with NSCLC benefit from this therapy. In order to overcome these limitations, a
novel multi-tier biotechnology treatment approach is proposed that includes: (1) suppression of all four types of
EGFR-TKs by a pool of small interfering RNAs (siRNAs); (2) induction of cell death by an anticancer drug, (3)
enhancing the efficiency of the treatment by the local inhalatory delivery of therapeutic agents to the lungs
(passive targeting), (4) active receptor-mediated targeting of the therapy specifically to cancer cells and (5)
increasing the stability, solubility, and cellular penetration of siRNA and drug by using Nanostructured Lipid
Carriers (NLC). We hypothesize that the application of this nanotechnology-based tumor-targeted,
multifunctional approach will substantially enhance the efficiency of the treatment of NSCLC and
reduce adverse side effects of chemotherapy. The main objective of the current research is to test the
stated hypothesis and develop a novel nanoscale-based technology to carry out proof-of-concept of the
proposed strategy. The specific aims of the proposed research are: (1) to engineer, synthesize, and
characterize a multifunctional, multicomponent Delivery System (DS) containing NLC, a pool of siRNAs
targeted to EGFR-TKs, paclitaxel (TAX) as an anticancer drug, and a Luteinizing Hormone-Releasing
Hormone (LHRH) peptide as a targeting moiety specific to receptors overexpressed in lung cancer cells; (2) to
examine efficiency of active (LHRH receptor-mediated) and passive (local inhalation delivery) dual tumor
targeting of NLC-based DS; (3) to characterize the efficiency of combinatorial gene and chemotherapy for
silencing of EGFR-TK signaling pathways and cell death induction; (4) to evaluate in vivo antitumor activity and
adverse side effects of targeted and non-targeted NLC-based DS in clinically relevant orthotopic mouse
models of primary human NSCLC xenografts. It is expected that the proposed approach and the use of the
developed multifunctional NLC-based DS will substantially enhance the efficiency of therapy of NSCLC and
limit adverse side effects of the treatment. Experimental data obtained will provide the proof-of-concept of the
proposed approach, and can potentially make a considerable impact on the field of drug delivery and improve
the efficiency of therapy for lung and other types of cancer.
项目名称:生物纳米技术治疗肺癌
项目摘要
肺癌是全球癌症相关死亡的主要原因。非小细胞肺癌
非小细胞肺癌(NSCLC)是最常见的肺癌类型,占所有肺癌病例的80%以上。
化疗是NSCLC的主要术前和术后治疗。然而,
化疗在大多数患者中仍然相对较低,并且受到特异性不足、低药物敏感性和低剂量的限制。
累积和滞留在肺部,具有严重的治疗副作用。近日,小
分子酪氨酸激酶(TK)抑制剂,其作用于表皮生长因子受体(EGFR),
用于治疗NSCLC。然而,即使是最新一代的EGFR抑制剂,
全身毒性,并且在预防非典型EGFR信号传导方面无效。结果只有
大约10%的NSCLC患者受益于该疗法。为了克服这些限制,
提出了一种新的多层生物技术处理方法,包括:(1)抑制所有四种类型的
EGFR-TK通过小干扰RNA(siRNA)池;(2)抗癌药物诱导细胞死亡,(3)
通过将治疗剂局部吸入递送至肺来提高治疗效率
(被动靶向),(4)主动受体介导的治疗特异性靶向癌细胞,和(5)
通过使用纳米结构脂质增加siRNA和药物的稳定性、溶解性和细胞渗透性
运营商(NLC)。我们假设,这种基于纳米技术的肿瘤靶向,
多功能方法将大大提高NSCLC治疗的效率,
减少化疗的副作用。本研究的主要目的是测试
陈述的假设,并开发一种新的基于纳米尺度的技术来进行概念验证,
提出的战略。本研究的具体目标是:(1)工程化、合成化,
表征含有NLC的多功能、多组分递送系统(DS),
靶向EGFR-TK,紫杉醇(TAX)作为抗癌药物,和促黄体生成激素释放因子
激素(LHRH)肽作为对肺癌细胞中过表达的受体具有特异性的靶向部分;(2)
检查主动(LHRH受体介导)和被动(局部吸入递送)双重肿瘤的效率
靶向基于NLC的DS;(3)表征组合基因和化疗的效率,
EGFR-TK信号传导途径的沉默和细胞死亡诱导;(4)评估体内抗肿瘤活性,
靶向和非靶向基于NLC的DS在临床相关原位小鼠中的不良副作用
原发性人NSCLC异种移植物的模型。预计所提出的方法和使用
开发的基于NLC的多功能DS将大大提高NSCLC的治疗效率,
限制治疗的不良副作用。所获得的实验数据将提供
提出的方法,并可能对药物递送领域产生相当大的影响,并改善
治疗肺癌和其他类型癌症的效率。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations.
- DOI:10.3390/pharmaceutics13071063
- 发表时间:2021-07-11
- 期刊:
- 影响因子:5.4
- 作者:Majumder J;Minko T
- 通讯作者:Minko T
Nanotechnology-Based Nucleic Acid Vaccines for Treatment of Ovarian Cancer.
- DOI:10.1007/s11095-022-03434-4
- 发表时间:2023-01
- 期刊:
- 影响因子:3.7
- 作者:Gildiz, Simav;Minko, Tamara
- 通讯作者:Minko, Tamara
Plant-derived single domain COVID-19 antibodies.
- DOI:10.1016/j.jconrel.2023.05.030
- 发表时间:2023-07
- 期刊:
- 影响因子:0
- 作者:Shen AM;Malekshah OM;Pogrebnyak N;Minko T
- 通讯作者:Minko T
Anti-Tumor Effects of a Penetratin Peptide Targeting Transcription of E2F-1, 2 and 3a Is Enhanced When Used in Combination with Pemetrexed or Cisplatin.
- DOI:10.3390/cancers13050972
- 发表时间:2021-02-26
- 期刊:
- 影响因子:5.2
- 作者:Rather GM;Anyanwu M;Minko T;Garbuzenko O;Szekely Z;Bertino JR
- 通讯作者:Bertino JR
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Tamara Minko其他文献
Tamara Minko的其他文献
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{{ truncateString('Tamara Minko', 18)}}的其他基金
Nanotechnology-based personalized treatment of metastatic ovarian cancer
基于纳米技术的转移性卵巢癌个体化治疗
- 批准号:
10634555 - 财政年份:2022
- 资助金额:
$ 58.12万 - 项目类别:
Nanotechnology-based personalized treatment of metastatic ovarian cancer
基于纳米技术的转移性卵巢癌个体化治疗
- 批准号:
10417379 - 财政年份:2022
- 资助金额:
$ 58.12万 - 项目类别:
Bionanotechnology approach for treatment of lung cancer
生物纳米技术治疗肺癌的方法
- 批准号:
10328899 - 财政年份:2019
- 资助金额:
$ 58.12万 - 项目类别:
Bionanotechnology approach for treatment of lung cancer
生物纳米技术治疗肺癌的方法
- 批准号:
10094206 - 财政年份:2019
- 资助金额:
$ 58.12万 - 项目类别:
Tumor-targeted nanoparticle-based delivery system for imaging and treatment of cancer
用于癌症成像和治疗的肿瘤靶向纳米粒子递送系统
- 批准号:
9899949 - 财政年份:2017
- 资助金额:
$ 58.12万 - 项目类别:
Tumor-targeted nanoparticle-based delivery system for imaging and treatment of cancer
用于癌症成像和治疗的肿瘤靶向纳米粒子递送系统
- 批准号:
10115624 - 财政年份:2017
- 资助金额:
$ 58.12万 - 项目类别:
Nanotechnology Approach for Inhalation Treatment of Pulmonary Fibrosis
纳米技术吸入治疗肺纤维化的方法
- 批准号:
8786479 - 财政年份:2014
- 资助金额:
$ 58.12万 - 项目类别:
Nanotechnology Approach for Inhalation Treatment of Pulmonary Fibrosis
纳米技术吸入治疗肺纤维化的方法
- 批准号:
8631723 - 财政年份:2014
- 资助金额:
$ 58.12万 - 项目类别:
Multifunctional Nanotherapeutics for Cancer Treatment and Imaging
用于癌症治疗和成像的多功能纳米疗法
- 批准号:
8267083 - 财政年份:2010
- 资助金额:
$ 58.12万 - 项目类别:
Multifunctional Nanotherapeutics for Cancer Treatment and Imaging
用于癌症治疗和成像的多功能纳米疗法
- 批准号:
8676693 - 财政年份:2010
- 资助金额:
$ 58.12万 - 项目类别:
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