近红外光响应智能pNNAU-anti-EpCAM纳米凝胶载Docetaxel体系的构建及其抗三阴性乳腺癌的作用机制研究

批准号:
82003315
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
高永峰
依托单位:
学科分类:
肿瘤大数据与人工智能
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
高永峰
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中文摘要
三阴性乳腺癌(TNBC)作为乳腺癌中最“毒”的亚型,具有易转移、易复发且生存期短的临床特征。化疗仍然是TNBC主要的治疗手段,但全身化疗不良反应重,疗效不尽人意。因此,构建智能靶向递药体系,实现常规化疗药物的增效减毒,已成为提高TNBC疗效的研究热点之一。申请者长期从事纳米凝胶相关研究工作,最近的预实验制备了紫外光响应性pNIPAm-co-NBMA纳米凝胶粒子。据此,本项目拟首先将具有近红外光响应和EpCAM靶向的基元构建到该粒子中,利用纳米凝胶网络及特异性相互作用力实现常规化疗药物如Docetaxel的负载;其次,利用原子力显微镜和表面力仪探讨纳米凝胶与TNBC细胞及正常组织细胞间的微观作用力及机理;最后通过构建TNBC原位移植瘤模型,评估智能纳米凝胶载药系统对TNBC肿瘤示踪及生长的影响。该研究有望为改善TNBC患者的治疗效果提供新的策略。
英文摘要
As a special subtype of breast cancer, triple negative breast cancer (TNBC) has the clinical characteristics of easy metastasis, easy recurrence and short survival time. Right now, Chemotherapy is still the main treatment of TNBC. However, several serious drawbacks make systemic chemotherapy with low treatment efficiency, such as adverse reactions. Therefore, building an intelligent targeted drug delivery system to achieve the synergistic detoxification of conventional chemotherapy drugs has become one of the important research topics to improve the treatment of TNBC. The applicant has been engaged in nanogel-related research work for a long time, and recently, the preliminary experiments showed UV-responsive pNIPAm-co-NBMA nanogel particles were successfully synthesized. Based on this results, the project here intends to do the followings: First, incorporating near-infrared light response unit and EpCAM targeting unit into the particle, by using the nanogel network and specific interaction force to achieve the loading of conventional chemotherapy drugs, such as Docetaxel; Second, exploring the internal forces and mechanism between nanogel and TNBC/normal tissue cells by atomic force microscope and surface force instrument; Finally, by constructing TNBC orthotropic tumor model, evaluating the smart nanogel drug loading system for TNBC tumor tracking and inhibition of growth. This study is expected to provide new strategies for improving the therapeutic effect of TNBC patients.
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