基于石墨烯光声转换用于增强前列腺癌光声成像及光热/CO协同治疗机制

Prostate cancer caused seriously harmful to the health of elderly man, to design and fabricate a nano-theranostic agent with diagnosis and therapeutical effect together, which was one of the important early diagnosis and treatments for prostate cancer. In previous study, we had fabricated nano-graphene oxide (NGO), with the photo-thermal and photo-acoustic effect, but tumor wasn’t to be completely ablated by photothermal therapy alone. Based on the theory that carbon monoxide (CO) inhibits the growth of prostate cancer by the anti-Warburg effect, we propose the hypothesis: the grapheme-based CO nano-theranostic agent, one of chelate polymers with NGO, CO-releasing molecule and RGD, with the integrated function of enhanced photoacoustic imaging of prostate cancer and photo-thermal/CO synergistic therapy. Both the type and composition of the nano-theranostic agent will be carefully varied for seeking out the optimal utility in biocompatibility，targeting and on-demand release of CO in vitro and vivo. In addition, the mechanism of photo-acoustic and photo-thermal/CO synergistic therapy will be investigated. This project could provide a novel model for the theranostic of prostate cancer.

前列腺癌严重危害中老年男性生命健康，设计制备兼具诊断和治疗为一体的纳米诊疗剂，是前列腺癌早期诊断与治疗的重要方法。项目组前期已成功制备出具有光热和光声效应的氧化石墨烯纳米片，但单纯光热治疗难以达到肿瘤完全消融。基于一氧化碳（CO）可通过抗Warburg效应抑制前列腺癌细胞生长，为此，提出假说：以氧化石墨烯纳米片螯合光敏型CO释放分子（CORM），并结合靶向前列腺癌的RGD配体，制备的石墨烯基CO纳米诊疗剂具有增强前列腺癌光声成像效果和光热/CO协同治疗作用。为验证假说，项目拟进行石墨烯基CO纳米片化学组成和结构的调控，筛选最佳结构参数，体外、体内环境下分析石墨烯基CO纳米片的生物相容性、靶向性、光声系统下CO释放可控性，并探讨相关光声成像及光热/CO协同治疗机制。项目的开展为前列腺癌诊疗一体化提供了新的思路。

肿瘤的早期准确诊断和高效治疗一直是肿瘤诊治中的难题。随着纳米技术的发展，兼具光学成像高对比度和声学成像中深穿透特性和高分辨率等优点的光声成像，以及无创而精准的声动力疗法是近十年来发展最迅速的生物医学诊疗技术，为临床肿瘤诊治提供了一个新的发展方向。. 我们利用 NbC2 二维纳米片为载体担载 TiO2 和谷胱甘肽（GSH）合成 抑制剂—BSO，成功构建出具有光声成像和提高 SDT 治疗效果的肿瘤纳米诊疗平台；进一步利用 L-精氨酸(LA)中的胺对 CO2 的可逆吸附，将 LA 与原卟啉(PpIX)封装在介 孔有机硅纳米粒子(MONs)中，制备了一种纳米复合材料（MON-PpIX-LA-CO2）该材料在超声照射下可连续释放 CO2，可持续产生空化，促进更多的 ROS 产生，杀死肿瘤细胞，抑制肿瘤生长，增强 SDT 同时促进肿瘤细胞免疫源性死亡。为实现肿瘤诊疗的精准性和有效性提供新思路。