Nanoparticle contrast agents for earlier breast cancer detection

项目总结 到目前为止，乳腺癌是最常见的癌症类型，是女性第二致命的癌症。 早期发现乳腺癌的乳房X光检查项目很普遍。乳房X光摄影 筛查可以降低乳腺癌的死亡率，而且具有成本效益。然而，有消息称， 乳房致密的女性(约占女性的10%)乳房X光检查不是很有效，敏感度为30%- 60%。此外，与较低的肿瘤检测机会无关，乳房致密的女性处于 患乳腺癌的风险更高。因此，为了降低这一人群中乳腺癌的死亡率，更好地 筛选技术是必要的。 双能量乳房X光检查是最近出现的一种高度敏感和特异的技术 检测乳房致密的女性的癌症。一种用于双能量乳房X光摄影的造影剂，可以 对于乳房致密的女性以及特定的高危人群，确定肿瘤是非常有益的。 人口。目前已有的碘基造影剂药代动力学较差，肿瘤发生率低 在许多患者中有积聚和禁忌症。而其他技术，如对比度增强 MRI可用于乳房致密女性筛查，费用高实用障碍阻碍 这些技术的使用。 在此，我们建议开发新型的、可生物降解的银基纳米颗粒(SBNP)，以实现安全检测 乳腺癌风险较高的患者中的肿瘤。我们已经发现，银是一种能产生 双能量乳房X光摄影的卓越对比度一种新的乳房X光摄影技术，两幅图像 在不同的X射线能量下获得。我们已经找到了使纳米颗粒稳定和 生物相容。我们选择了一种相对简单但灵活的纳米颗粒设计，以改进 翻译的可能性。纳米颗粒应该会在肿瘤中迅速积聚，使它们 在乳房X光检查中很明显，然后逐渐分解成肾脏排泄的成分。这 该提案解决了在癌症中使用纳米颗粒的一个关键挑战：排泄。作为该提案的一部分 我们将开发一种可生物降解的载体系统，该系统可以将小的、高度亲水的纳米颗粒输送到 肿瘤，在分解和肾脏排泄之前。这一运输系统可能会产生广泛的影响，因为它可能 可应用于多种不同的纳米颗粒类型和抗癌方法。

PROJECT SUMMARY Breast cancer is by far the most common type of cancer and is the second most deadly cancer in women. Breast cancer mammography screening programs for early detection are widespread. Mammography screening reduces mortality from breast cancer and is cost-effective. However, it has emerged that mammography is not very effective in women with dense breasts (about 10% of women), with sensitivity of 30- 60%. Moreover, independent of the lower chance of tumor detection, women with dense breasts are at a higher risk of breast cancer. Therefore to reduce mortality from breast cancer in this population, better screening techniques are needed. Dual-energy mammography has recently emerged as a technique that is highly sensitive and specific for detecting cancer in women with dense breasts. A contrast agent for dual-energy mammography that can identify tumors would be highly beneficial in women with dense breasts, as well as in selected high-risk populations. Currently available iodine-based contrast agents have poor pharmacokinetics, low tumor accumulation and are contraindicated in many patients. While other techniques such as contrast-enhanced MRI can be used for screening women with dense breasts, the high costs and practical obstacles prevent the use of those techniques. We herein propose to develop novel, biodegradable silver-based nanoparticles (SBNP) to allow safe detection of tumors in patients at higher risk of breast cancer. We have found that silver is an element that produces excellent contrast in dual-energy mammography a new variation of mammography where two images are acquired at different x-ray energies. We have found methods that make the nanoparticles stable and biocompatible. We have chosen a comparatively simple, yet flexible nanoparticle design in order to improve the likelihood of translation. The nanoparticles should quickly accumulate in tumors, rendering them conspicuous on mammography, before gradually breaking down into their components for renal excretion. This proposal addresses a key challenge in the use of nanoparticles in cancer: excretion. As part of this proposal we will develop a biodegradable carrier system that can deliver small, highly hydrophilic nanoparticles to tumors, before breakdown and renal excretion. This carrier system could have a broad impact, since it could be applied to numerous different nanoparticle types and anti-cancer approaches.