PHOTOTHERMAL-CHEMOTHERAPY OF MELANOMA W/ CISPLATIN-LOADED HOLLOW GOLD NANOSPHERE

负载顺铂的空心金纳米球光热化疗治疗黑色素瘤

• 批准号: 8360094
• 负责人: WEI LU
• 金额: $ 12.55万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360094
• 关键词: Behavioral Research; Biomedical Research; Cisplatin; Drug Controls; Drug Formulations; Drug Modulation; Funding; Gold; Grant; Homing; Lasers; Lead; Malignant Neoplasms; Nanosphere; Nanotechnology; National Center for Research Resources; Optics; Patients; Penetration; Peptides; Principal Investigator; Property; Recurrent tumor; Research; Research Infrastructure; Resistance; Resources; Shapes; Source; Surface Plasmon Resonance; Techniques; Technology; Tissues; Toxic effect; Treatment Protocols; United States National Institutes of Health; absorption; alpha-Melanocyte stimulating hormone; base; chemotherapy; cost; design; glutamyl-glutamic acid; intravenous administration; melanoma; nanoparticle; particle; success; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Hollow gold nanospheres (HAuNS) possess a unique combination of small size (~40 nm), spherical shape, hollow interior, and strong surface plasmon resonance at near-infrared (NIR) region wavelengths (~800 nm), wherein optical absorption in tissue is minimal and penetration is optimal. We propose to develop a multi-modulated nanotechnology which could be applied to concurrent photothermal therapy and chemotherapy of melanoma. This technology is based on the formulation of cisplatin-loaded HAuNS, where a small peptide, Ac-Glu-Glu-Cys-NH2 (EEC), is designed to serve as both cisplatin coordinator and linker to gold nanoparticles. [Nle4,D-Phe7] alphamelanocyte-stimulating hormone (NDP-MSH) peptide will be conjugated on the particles as melanoma homing moiety. Through intravenous administration, dual modulation of the drug-loaded nanoparticle will be investigated. First, the particles are expected to have tumor targeting effect and sustained release properties promoting superior anticancer effect and decreased toxicity. Second, upon NIR laser modulation, the combination of photothermal therapy with HAuNS and chemotherapy with laser-controlled drug release may produce a synergistic anticancer effect to overcome tumor regrowth and cisplatin resistance. The success of this technique will be viewed as a paradigm in the treatment of accessible recurrent neoplasms and lead to more effective and patient-compliant treatment over exisitng treatment protocols. This technology may be further explored for application to other cancers and has the potential to produce a major impact in cancer-relevant research.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 中空金纳米球（HAuNS）具有小尺寸（~40 nm）、球形形状、中空内部和在近红外（NIR）区域波长（~800 nm）处的强表面等离子体共振的独特组合，其中组织中的光学吸收最小并且穿透最佳。我们建议开发一种多重调制的纳米技术，可应用于同步光热治疗和化疗的黑色素瘤。该技术基于顺铂负载的HAuNS的制剂，其中小肽Ac-Glu-Glu-Cys-NH 2（EEC）被设计为充当顺铂配位体和金纳米颗粒的连接体。[Nle4，D-Phe 7] α促黑素细胞激素（NDP-MSH）肽将作为黑素瘤归巢部分缀合在颗粒上。通过静脉内给药，将研究载药纳米颗粒的双重调节。首先，预期颗粒具有肿瘤靶向作用和持续释放性质，从而促进上级抗癌作用和降低的毒性。其次，在NIR激光调制后，光热疗法与HAuNS和化疗与激光控制的药物释放的组合可以产生协同抗癌作用，以克服肿瘤再生长和顺铂耐药性。该技术的成功将被视为治疗可触及复发性肿瘤的范例，并导致比传统治疗方案更有效和患者依从性更高的治疗。这项技术可以进一步探索应用于其他癌症，并有可能在癌症相关研究中产生重大影响。