核靶向多功能纳米颗粒增强DNA辐射损伤的实验性研究

The rapid development of nanotechnology provides a solution to achieve the accurate diagnosis and efficient therapy of diseases. Due to the protection mechanism, it is difficult for free anticancer drugs to locate the nucleus and induce direct DNA damage. Based on the up-conversion nanoparticles (UCNPs), we designed a TAT peptide-conjugated intra-nuclear drug delivery, which was the integration of the magnetic/luminescent dual-mode imaging core and mesoporous silica for delivering drugs. The synergetic chemo-/radiotherapy of the multifunctional nanotheranostics were investigated under the condition of radiation. Not only did the constructure serve as a imaging probe for the location of tumors in vivo, the release and distriberution of drugs was analyzed with a hard X-ray microprobe to assess the efficiency of targetability directed by TAT peptide. It will present the underlying mechanism of synergistic effect of radiotherapy and chemotherapy. Using the single particle microbeam irradiation technique, radiation-induced DNA damage was to evaluate the synergetic effect of whether the anticancer drugs accumulated in the nuclear or not. The results will provide more exciting opportunities in treating cancer disease by accurate diagnosis and micro precision treatment.

纳米技术的快速发展为疾病救治提供了诊疗一体化的解决方案。然而由于细胞核的自身保护机制，使得抗肿瘤药物不能有效进入细胞核，g不能完成以诱导DNA损伤为作用机理的抗肿瘤作用。本项目拟设计一种以核磁共振/荧光——双模式成像的UCNPs为内核，在其外部的介孔氧化硅壳层装载能够引起DNA损伤的抗肿瘤药物，并在表面修饰TAT多肽，使其具有细胞核靶向性，并观察该多功能纳米颗粒在外部放射治疗条件下的辐射增敏作用。该项目不仅实现了肿瘤组织结构的定位诊断，而且通过X-线测绘技术可以从微观水平了解细胞核导向的药物载体在细胞内部的药物释放与分布情况，阐明与放疗相结合的协同作用机理，并且结合单粒子微束照射技术，客观评价化疗药物是否入核对放疗增敏作用的影响。这将为肿瘤的精确诊断和精准治疗提供客观依据。