OTHER FUNCTIONS "TARGET SPECIFIC AND DRUG LOADED IRON OXIDE NANOPARTICLES FOR CA

乳腺癌是最常见的癌症类型，也是女性癌症死亡的第二大原因，全球每年有100多万新病例和37万人死亡。化疗药物，如阿霉素，已用于手术前和手术后的辅助治疗，或作为乳腺癌转移患者的主要治疗选择。尽管最近在联合化疗药物方面的进展提高了乳腺癌患者的生存率，但仍有很高比例的患者对化疗药物产生抗药性，并导致治疗失败。因此，迫切需要有效治疗乳腺癌的新方法来提高治疗效果。本项目旨在开发一种阿霉素载药靶向磁性纳米氧化铁(IONP)平台，用于乳腺癌的靶向治疗。所提出的纳米片可以系统地递送并选择性地在原发和转移的肿瘤部位蓄积，然后通过内吞作用内化到乳腺癌细胞中。IONP在肿瘤细胞和肿瘤环境中的选择性浓缩产生了强大的MRI对比度，用于通过MR成像检测肿瘤病变中的药物输送和反应。在证明了工程纳米片可以在动物模型中靶向肿瘤的可行性之后，SBIR第二阶段项目的目标是通过进一步优化靶向治疗纳米片平台的有效性、生物分布、毒性、药动学/药效学研究和未来的临床试验，扩大对第一阶段研究中的成功研究的调查，并将该平台转化为临床前试验和商业化。

Breast cancer is the most common type of cancer and the second leading cause of cancer death among women with more than one million new cases and 370,000 deaths worldwide yearly. Chemotherapy drugs, such as Doxorubicin, have been used in both pre- and post-operative adjuvant therapy or as the main therapeutic option for breast cancer patients with metastatic disease. Although recent advances in the combination of chemotherapy drugs have improved survival for breast cancer patients, a high percentage of patients develop resistance to chemotherapeutic agents and fail treatment. Therefore, novel approaches for the effective treatment of breast cancer are urgently needed to improve the therapeutic response. This project aims to develop a Doxorubicin loaded and target specific magnetic iron oxide nanoparticle (IONP) platform for targeted therapy of breast cancer. The proposed nanodrug can be systemically delivered and selectively accumulated at the primary and metastatic tumor sites and subsequently internalized into breast cancer cells via endocytosis. Selective enrichment of the IONP in tumor cells and the tumor environment produces strong MRI contrast for the detection of drug delivery and response in the tumor lesions by MR imaging. After demonstration of the feasibility that the engineered nanodrug can target the tumor in an animal model, the goal of this SBIR Phase II project is to extend the investigation of the successes in the Phase I study and move closer to translating this platform into preclinical trials and commercialization by further optimizing the targeted theranostic nanodrug platform for efficacy, biodistribution, toxicity, pharmacokinetics/pharmacodynamic studies, and future clinical trials.