Targeted Delivery of Nanodiamonds for Breast Cancer Imaging and Therapy

用于乳腺癌成像和治疗的纳米金刚石靶向输送

• 批准号: 9063541
• 负责人: Laura K. Moore
• 金额: $ 2.7万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9063541
• 关键词: Amides; Animal Cancer Model; Animal Model; Animals; Anthracyclines; Antibodies; Biological Products; Blood Circulation; Breast Cancer Cell; Breast Cancer therapy; Carbon; Cell Line; Cells; Cetuximab; Collaborations; Combined Modality Therapy; Contrast Media; Coupled; Cultured Cells; Detection; Diagnostic Imaging; Disease; Drug Kinetics; Drug toxicity; Engineering; Epidermal Growth Factor; Epidermal Growth Factor Receptor; Epirubicin; Estrogens; Evaluation; FDA approved; Flow Cytometry; Fluorescence; Gadolinium; Goals; Health; Hormonal; Hormones; Image; In Vitro; Label; Laboratories; MCF7 cell; MDA MB 231; Magnetic Resonance Imaging; Malignant Neoplasms; Mass Spectrum Analysis; Methods; Monitor; Monoclonal Antibodies; Movement; Mus; Neoplasm Metastasis; Nucleic Acids; Patients; Permeability; Pharmaceutical Preparations; Plasma; Polymers; Progesterone; Proteins; Research; Resistance; Safety; Surface; System; Techniques; Therapeutic; Therapeutic antibodies; Toxic effect; Treatment Efficacy; Tumor Biology; Universities; antibody conjugate; base; biomaterial compatibility; cancer imaging; cancer therapy; carboxylate; chemotherapeutic agent; experience; fluorescence imaging; fluorophore; gadolinium oxide; imaging agent; improved; in vivo; interest; malignant breast neoplasm; nano; nanoparticle; nanoscale; overexpression; particle; receptor; small molecule therapeutics; targeted delivery; targeted treatment; triple-negative invasive breast carcinoma; tumor; tumor xenograft

DESCRIPTION (provided by applicant): TNBCs present an interesting treatment paradox in that they are highly aggressive tumors that tend to be relatively chemosensitive. However, as they do no express estrogen, progesterone or epidermal growth factor type 2 receptors (ER, PR and Her2/Erbb2 respectively) patients with these cancers do not benefit from the typical hormonal modulations used to treat breast cancers. While TNBCs fail to express a variety of hormonal receptors, they typically overexpress the type 1 epidermal growth factor type 1 receptors (EGFR/Erbb1) and therefore could potentially benefit from EGFR targeted therapies. Here we seek to improve the imaging and treatment of triple negative breast cancers (TNBCs) with the utilization of NDs as delivery vehicles targeted to the epidermal growth factor receptor (EGFR). Nanodiamonds (NDs) have emerged as attractive nano-vehicles for both imaging and therapy due to their innate biocompatibility, scalable synthetic methods and unique carbon surface that facilitates bio agent attachment. Furthermore, ND attachment has been shown to enhance imaging efficiency, sustain drug release, boost therapeutic efficacy, overcome cellular resistance and improve drug safety profiles in both cell based and animal models. This project will build upon the already promising ND-based delivery system with the addition a targeting method, in this case the FDA-approved therapeutic antibody to EGFR, Cetuximab (CXB). Antibody-based targeting of ND-conjugates for imaging should allow for detailed tumor imaging, thereby improving diagnostic imaging, detection of metastases, tumor margin assessment and monitoring of therapy progression. Furthermore, antibody-based targeting of therapeutic NDs will allow for broader application of ND conjugates. NDs have been shown to be highly effective at delivering chemotherapeutic agents by passive targeting to tumors that experience the enhanced permeability and retention effect (EPR). As not all tumors experience EPR, active targeting mechanisms such as antibody attachment could enable the application of ND-conjugates in a wider variety of disease states. Additionally, if the targeting antibody is also therapeutic, as is the case here, targeted particle delivery will also serve as combination therapy.

描述（由申请人提供）：TNBC提出了一个有趣的治疗悖论，因为它们是高度侵略性的肿瘤，往往相对化学敏感。但是，由于它们没有明确的雌激素，孕酮或表皮生长因子2型受体（分别为ER，PR和HER2/ERBB2）患者，这些癌症不会受益于用于治疗乳腺癌的典型激素调节。尽管TNBC无法表达各种激素受体，但它们通常过表达1型表皮生长因子1型受体（EGFR/ERBB1），因此可能会受益于EGFR靶向疗法。在这里，我们试图通过使用NDS作为表皮生长因子受体（EGFR）的递送车的利用来改善三重负乳腺癌（TNBC）的成像和处理。由于其先天的生物相容性，可伸缩的合成方法和独特的碳表面，纳米座（NDS）已成为用于成像和治疗的有吸引力的纳米车辆，可促进生物剂的附着。此外，已显示ND附着可以提高成像效率，维持药物释放，提高治疗功效，克服细胞耐药性并改善基于细胞和动物模型的药物安全概况。 该项目将以添加的靶向方法为基于已经有希望的基于ND的交付系统，在这种情况下为FDA批准的与EGFR Cetuximab（CXB）的治疗抗体。基于抗体的ND偶联物用于成像的靶向应允许详细的肿瘤成像，从而改善诊断成像，检测转移，肿瘤边缘评估和治疗进展的监测。此外，基于抗体的治疗NDS靶向将允许更广泛地应用ND结合物。通过被动靶向肿瘤，NDS已被证明在传递化学治疗剂方面非常有效，这些肿瘤经历了增强的渗透性和保留效应（EPR）。由于并非所有肿瘤都经历EPR，因此主动靶向机制（例如抗体附着）可以使ND偶联物在更广泛的疾病状态中应用。此外，如果靶向抗体也是治疗性的，那么在这里，靶向颗粒递送也将作为联合治疗。