Precision nanotherapeutics for cancer treatment

乳腺癌是最常见的癌症，也是癌症相关死亡的主要原因之一 在女人身上。约80-85%的乳腺癌表达雌激素受体（ER）、孕激素受体（PR）， (PR)或激素表皮生长因子受体2（HER-2）。这些ER、PR和HER-2受体使 通过设计可以识别这些受体的治疗方法进行靶向治疗。一个小的亚型， 不表达ER、PR和HER-2，并且缺乏所有三种受体，称为三阴性乳腺癌（TNBC）。 TNBC占所有乳腺癌的约10-15%。针对这些受体的绝大多数疗法 不能用于临床治疗TNBC。与其他乳腺癌相比， 激素疗法或HER-2靶向疗法，TNBC的存活率要低得多， 治疗后复发并扩散到乳房以外。目前临床上对TNBC的治疗主要是 局限于基于常规小分子化学治疗剂如紫杉醇的方案。在 事实上，紫杉醇已被用作TNBC的一线治疗，并被推荐用于所有治疗线， 乳腺癌然而，像许多小分子化学治疗剂一样，紫杉醇具有短的循环半衰期 并且在实体瘤中渗透和保留能力非常差。紫杉醇制剂， TNBC在肿瘤中的有效性和改善的渗透性可能导致更有效的治疗。的目标 这个R 01项目是开发紫杉醇-二氧化硅纳米颗粒，一种尺寸精确控制的纳米药物 可能比紫杉醇更有效地治疗TNBC。我们将首先探索这些的控制合成 纳米医学，确定尺寸范围和表面性质，以实现TNBC的最佳治疗。我们将使用三个 图10示出了代表性TNBC模型、MDA-MB-231原位模型、4 T1转移性TNBC模型和患者TNBC模型。 衍生的异种移植模型，用于完整评价紫杉醇-二氧化硅纳米颗粒的治疗功效。 最后，我们将讨论纳米药物的安全性问题，并探讨其分子和病理学机制。 纳米药物治疗TNBC的机制。

Breast cancer is the most frequently diagnosed cancer and one of the leading causes of cancer related death in women. About 80-85% of all breast cancers have expressed estrogen receptor (ER), progesterone receptor (PR), or hormone epidermal growth factor receptor 2 (HER-2). These ER, PR and HER-2 receptors enable targeted treatment by designing therapeutics that can recognize these receptors. One small subtype, which do not express ER, PR and HER-2 and lack all three receptors, is called Triple negative breast cancer (TNBC). TNBC represents about 10-15% of all breast cancers. The vast majority of therapies targeting these receptors cannot be used for treating TNBC in clinic. Compared to other breast cancers that can be effectively treated by hormonal therapies or HER-2 targeted therapies, TNBC has a much lower survival rate, and is more likely to recur after treatment and to spread beyond the breast. Current treatment of TNBC in clinic has been largely limited to regimens based on conventional small molecule chemotherapeutic agents, such as paclitaxel. In fact, paclitaxel has been used as a first-line treatment for TNBC and is recommended for all lines of therapy to breast cancer. However, like many small molecule chemotherapeutics, paclitaxel has short circulation half-life and very poor penetration and retention capability in solid tumors. A paclitaxel formulation with more sustained availability and improved penetration in the tumors of TNBC may result in more effective treatment. The goal of this R01 project is to develop paclitaxel-silica nanoparticles, a class of size precisely controlled nanomedicine that may treat TNBC more effectively than paclitaxel. We will first explore the controlled synthesis of these nanomedicine, identify size range and surface property for optimal treatment of TNBC. We will then use three representative TNBCs, the MDA-MB-231 orthotopic model, the 4T1 metastatic TNBC model and the patient derived xenograft model, for complete evaluation of the therapeutics efficacy of paclitaxel-silica nanoparticle. Finally, we will address safety issue of the nanomedicine and explore the molecular and pathological mechanisms of nanomedicine in treating TNBCs.