碳化铁纳米材料微结构演化及其增强青蒿素抗肿瘤疗效研究

The cancer therapeutic effect of artemisinin, which is a tumor-selective drug, is clinically limited by the difficulty of drug enrichment at the tumor site and the low concentration of local ferrous ions. Benefiting from the superior magnetic property and the pH-controlled iron release ability of iron carbide nanoparticles (ICNPs), this problem can be solved by using ICNPs as the carrier and activity primer, to improve both the concentration and activity of artemisinin at the tumor site. In addition, the microstructures of ICNPs are not only complicated, but also associated with magnetic properties and acid sensitivities. In this project, by adjusting the reaction conditions, the evolutionary mechanism of ICNPs microstructure is to be studied, resulting in the harvest of several kinds of ICNPs with particular microstructures. By studying the influences of microstructure on the tumor targeting and iron release ability of ICNPs and discussing the way of ICNPs to affect the therapeutic effect of artemisinin, correlatations among microstructure of ICNPs, magnetic and ferrous ions releasing behavior of ICNPs, and the anti-tumor effect of artemisinin is designed to be established. Finally, ICNPs which can dramatically improve the cancer therapeutic effect of artemisinin are obtained. This project would provide experimental and theoretical basis for the better application of artemisinin in cancer therapy.

青蒿素是一类具有选择性肿瘤治疗效果的药物。然而其在肿瘤部位富集困难且活性受限于环境中的Fe2+浓度，导致其临床药效不甚理想。针对这一问题，本项目拟充分发挥碳化铁纳米材料优良的磁性能和酸敏感的Fe2+释放能力，将其用作青蒿素的载体与“活性引物”，提高青蒿素在肿瘤部位的浓度和药物活性，从而改善青蒿素的药效。此外，碳化铁纳米材料的微结构复杂，对材料的磁性和酸敏感性的影响规律尚不明确。为此，本项目拟通过控制碳化铁纳米材料制备过程的反应条件，获得不同微结构的碳化铁纳米材料，研究其微结构演化机制以及微结构与其理化性能、肿瘤处富集能力、Fe2+释放行为之间的关系，进而探讨碳化铁对青蒿素肿瘤治疗效果的影响，最终建立碳化铁纳米材料微结构-材料磁性能及其Fe2+释放行为-青蒿素抗肿瘤疗效之间的关联机制，优选出能增强青蒿素肿瘤治疗效果的碳化铁纳米材料，为青蒿素在抗肿瘤领域的应用研究提供实验基础和理论依据。

青蒿素是一类具有肿瘤选择性治疗效果的药物。然而其在肿瘤部位富集困难且活性受限于环境中的Fe2+浓度，导致其临床药效不甚理想。针对这一问题，本项目旨在充分发挥碳化铁纳米材料优良的磁性能和酸敏感的Fe2+释放能力，将其用作青蒿素的载体与“活性引物”，提高青蒿素在肿瘤部位的浓度和药物活性，从而改善青蒿素的抗肿瘤疗效。. 本项目通过控制碳化铁纳米材料制备过程中的反应条件，制备出Fe2C、Fe5C2、Fe3C三种相结构的碳化铁颗粒，并调控了纳米颗粒的尺寸、结晶性和结构。同时，通过跟踪不同反应条件下碳化铁纳米材料微结构的演变过程，阐明了微结构的演化机制。在此基础上，研究了不同相组成、结晶性、壳层包覆的碳化铁纳米材料的Fe2+释放行为、磁性能及其对青蒿素抗肿瘤疗效的影响，优化出非晶Fe3O4包覆、结晶性较弱的Fe2C纳米颗粒具有更高酸敏感性和磁性能，可在弱酸性条件下释放更多Fe2+，并阐明了微结构对其性能的影响。进一步考察了优选出的碳化铁纳米材料的青蒿素负载与释放性能，并在细胞和动物水平上评价疗效，建立了“碳化铁纳米材料微结构-材料磁性能及其Fe2+释放行为-青蒿素抗肿瘤疗效”三者之间的关联机制。最终获得磁性能强、能针对肿瘤环境释放Fe2+并能提高青蒿素抗肿瘤疗效的非晶Fe3O4包覆的Fe2C（Fe2C@Fe3O4）核壳结构碳化铁纳米材料。. 本项目的实施为青蒿素在抗肿瘤领域的应用研究提供实验基础和理论依据。