Precision nanotherapeutics for cancer treatment

乳腺癌是最常见的确诊癌症，也是癌症相关死亡的主要原因之一。 在女人身上。大约80%-85%的乳腺癌表达了雌激素受体(ER)、孕激素受体 (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 通过设计能够识别这些受体的治疗方法进行靶向治疗。一个很小的亚型，它可以 ER、PR和HER-2不表达，三种受体均缺失，称为三阴性乳腺癌(TNBC)。 TNBC约占所有乳腺癌的10%-15%。绝大多数针对这些受体的治疗 临床上不能用于治疗TNBC。与其他可以有效治疗的乳腺癌相比， 激素治疗或HER-2靶向治疗，TNBC的存活率要低得多，而且更有可能 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 仅限于基于常规小分子化疗药物的方案，如紫杉醇。在……里面 事实上，紫杉醇已经被用作治疗TNBC的一线药物，并被推荐用于所有治疗方法 乳腺癌。然而，像许多小分子化疗药物一样，紫杉醇的循环半衰期很短。 在实体肿瘤中的穿透和滞留能力非常差。一种更持久的紫杉醇制剂 可获得性和对TNBC肿瘤渗透率的提高可能会导致更有效的治疗。的目标是 这个R01项目是为了开发紫杉醇-二氧化硅纳米粒，一类尺寸精确控制的纳米药物 这可能比紫杉醇更有效地治疗TNBC。我们将首先探索这些化合物的受控合成 纳米药物，确定最佳治疗TNBC的大小范围和表面属性。然后我们将使用三个 具有代表性的TNBCs、MDA-MB-231原位模型、4T1转移TNBC模型和患者 派生异种移植模型，用于完整评价紫杉醇-二氧化硅纳米粒的治疗效果。 最后，我们将解决纳米药物的安全性问题，并探讨其分子和病理学 纳米药物治疗鼻咽癌的作用机制。

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.