基于碳纳米荧光颗粒的多步释放药物载体的构建及其在治疗乳腺癌中的应用研究

Nanotherapeutic agents have been employed in oncology for almost twenty years. Their localization following systemic injection is determined largely by the biological barriers they encounter. The major design parameters that govern the particle's ability to overcome biological barriers and localize in target organs are the particle geometry (size,shape) and surface chemistry (charge, hydrophobicity, affinity). Several strategies have been developed to provide ample opportunities for novel therapeutics in cancer and other pathologies. However, this is unlikely to be achievable by individual classes of particles, comprising a single material, regardless of their geometry and targeting specificity. Thus, novel strategies are needed, to develop truly general and fully personalized treatment regimens. Biological barriers are multifold, and sequential: thus, to attain generality of treatment, it is necessary to develop agents that are able to penetrate through a time sequence of barriers. Herein, based on fluorescent carbon nanoparticles, we try to develop novel multi-stage nanosystem, carrying both siRNA and chemotherapeutic drug, and apply to breast cancer therapy.

纳米药物在体内转运过程中会遭遇各种不同的生物障碍，需要制定相应的策略来克服，但是，有些策略是互相矛盾的，如逃避网状内皮系统需要聚乙二醇修饰，而聚乙二醇修饰不利于细胞摄取；逃避网状内皮系统最佳尺寸是100 nm，而肿瘤基质转运要求纳米颗粒越小越好，等等，将这些互相矛盾的策略集中到单一的纳米体系是不可能实现的，因此，需要发展新一代的智能纳米载药体系来解决矛盾，真正地实现高效的个体化肿瘤治疗。碳纳米材料作为重要的一类纳米材料，由于其生物低毒性和生物相容性，广泛地用于生物医学中。本课题将基于荧光碳纳米颗粒，设计和制备一种具有多步释放和靶向功能的全新药物载体，共同输运siRNA和化疗药物，应用于乳腺癌治疗。

作为一种新型的超小碳纳米颗粒，碳纳米荧光颗粒（Fluorescent Carbon Nanoparticles, FCNs），由于其独特的光学性质、良好的生物相容性和低毒性，使其在荧光标记、生物检测成像和药物载体等领域具有广泛的应用前景。本课题首先制备了多种不同荧光性能的FCNs，探讨了其发光机理。随后，我们重点研究了利用脂质体将FCNs包封进入内水相，并同时将抗癌药物盐酸阿霉素包封，最后通过改良工艺参数，提高了FCNs和阿霉素在脂质体中的包封率。我们希望该体系能成为一种多步释放载药体系，并应用于肿瘤治疗。

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