Nanoparticle contrast agents for earlier breast cancer detection

项目摘要 乳腺癌是迄今为止最常见的癌症类型，也是女性第二大致命癌症。 乳腺癌早期检测的乳房X线摄影筛查计划很普遍。乳腺摄影 筛查降低了乳腺癌的死亡率，具有成本效益。然而，已经出现的情况是， 乳房X光检查对乳腺致密的女性（约10%的女性）不是很有效，灵敏度为30- 百分之六十此外，独立于较低的肿瘤检出率，乳腺致密的女性在 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， 需要筛选技术。 双能量乳房X线摄影术最近已成为一种高度敏感和特异性的技术， 检测高密度乳腺妇女的癌症。一种用于双能量乳房X线摄影的造影剂， 识别肿瘤对乳腺致密的女性以及选定的高风险乳腺癌患者非常有益。 人口。目前可用的碘基造影剂具有差的药代动力学、低的肿瘤体积、低的肿瘤体积和低的肿瘤体积。 在许多患者中是禁忌的。而其他技术，如对比度增强 MRI可用于筛查乳腺致密的女性，但高成本和实际障碍阻碍了MRI的应用。 使用这些技术。 我们在此提出开发新型的、可生物降解的基于银的纳米颗粒（SBNP），以允许安全检测 乳腺癌风险较高的患者的肿瘤。我们发现银是一种能产生 双能量乳腺X射线摄影的出色对比度是一种新的乳腺X射线摄影变体， 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的方法， 生物相容性。我们选择了一种相对简单但灵活的纳米颗粒设计，以改善 翻译的可能性。纳米粒子应该很快在肿瘤中积累，使它们 在乳房X光检查中很明显，然后逐渐分解为肾脏排泄的成分。这 该提案解决了在癌症中使用纳米颗粒的关键挑战：排泄。作为这项提议的一部分， 我们将开发一种可生物降解的载体系统，可以将小的、高度亲水的纳米颗粒输送到 肿瘤，在分解和肾排泄之前。这种载体系统可能会产生广泛的影响，因为它可以 可以应用于许多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.