用于肺癌治疗聚合物修饰的介孔二氧化硅的电子束辐照合成与机理研究

The emergence of nanotechnology has brought new hope for cancer treatment. Nanomaterials have many advantages in the biomedical fields because of their unique physicochemical characteristics such as small size effect, quantum effect,and large specific surface areas, etc. In recent years, it has become a hot and difficult issue to develop a highly efficient, stable and biodegradable drug carrier for the treatment of malignant tumors. Among them, mesoporous silica nanoparticle (MSN) has been widely used as drug carrier, due to its controllable, tunable pore size and large specific surface area, easy modification and biological low toxicity, etc..In our work, we choose a novel rattle type mesoporous silica nanoparticle (Rattle-MSN) with excellent biocompatibility as the object of study to prepare polymer-modified Rattle-MSN through electron beam (EB)irradiation technique for the first time. From the view of the interdisciplinarity, we try to achieve the pH-responsive controlled drug release system by chemical tailoring and modifying the Rattle-MSN nanomaterials with polymers via EB technique. At the same time, the mechanisms of the synthesis, modification and pH-responsive controlled drug release about Rattle-MSN are also investigated in detail for further improving the biocompatibility and avoiding the low release rate, and pre-release of the drug delivery system. Finally, an efficient, stable, and biocompatible controlled drug delivery system will be obtained. The obtained materials will be further used in lung cancer therapy to investigate their drug release properties using doxorubicin (DOX) as a representative model drug. We believe that the results can not only provide the basic experimental datas for the impact of nanoparticles on human health in real environment, but the significant evidences for security applications of nanotechnology in cancer therapy, drug targeting and controlled release.

纳米技术的出现，为肿瘤治疗带来了新的希望。纳米材料因其独特的物化性质，在生物医学领域具有多种优势。近年来，开发在体内高效稳定并可代谢的药物载体材料用于恶性肿瘤的治疗，已成为相关领域研究的热点和难点。其中，介孔二氧化硅因其可控的形貌、可调的孔径和大的比表面积，易修饰及生物低毒性等优点，而被广泛用于药物载体的研究。鉴于此，申请人以成本低廉的夹心中空介孔二氧化硅作为研究对象，从学科交叉的角度出发，首次将电子束技术用于辐照改性聚合物修饰的介孔二氧化硅。通过辐照，优化介孔二氧化硅表面的聚合物网状结构，改变其交联度，实现药物的pH响应可控释放，揭示其合成、修饰及可控释放的机理，有效解决当前纳米药物载体生物兼容性差和前释放量大等问题，最终构建一种以电子束辐照改性技术制备的高效、稳定、生物兼容的可控的药物传输体系，并用于肺癌治疗的研究，为其在癌症治疗、药物靶向等方面的应用提供有力的理论支持和重要依据。

纳米技术的出现，为肿瘤治疗带来了新的希望。纳米材料因其独特的物理化学性质，在生物医学等领域具有多种优势。近年来，开发在体内高效稳定并可代谢的药物载体材料用于恶性肿瘤的治疗，已成为相关领域研究的热点和难点。其中，介孔二氧化硅因其可控的形貌、可调的孔径和大的比表面积，易修饰及生物低毒性等优点，而被广泛用于药物载体的研究。鉴于此，申请人以成本低廉的介孔二氧化硅作为研究对象，通过合成体系的探索，制备了具有多种形貌和结构的介孔二氧化硅纳米粒子，在优化合成工艺的基础上，结合各种表征手段，对介孔二氧化硅表面的生长过程进行了探讨。同时，以广谱抗癌药物阿霉素（DOX）和消炎镇痛药布洛芬（IBU）分别为药物分子模型，研究了不同体系制备的介孔氧化硅纳米粒子的药物负载和释放能力；以成人肝细胞L02和肺癌细胞A549分别为细胞模型，研究所得介孔氧化硅纳米粒子的生物兼容性和对癌细胞的抑制效果。有效解决当前纳米药物载体生物兼容性差和前释放量大等问题，最终构建一种高效、稳定、生物兼容的可控的药物传输体系，并用于肺癌治疗的研究，为其在癌症治疗和药物靶向等方面的应用提供有力的理论支持和重要依据。