高性能石墨烯量子点包覆的磁性金纳米星联合双歧杆菌用于喉癌治疗

Laryngeal cancer is a common head and neck malignancy. Radiotherapy and chemotherapy remain a popular choice for laryngeal cancer therapy. In this project, a novel strategy which applying drug-loaded particles triggered by magnetic field and near-infrared (NIR) laser for laryngeal cancer therapy was developed based on the frontier science in nanobiomedicine and our previous work. Two types of novel drug-loaded systems which are suitable for intratumoral and intravenous injections, respectively, will be prepared. One drug loaded system for intratumoral injection contains magnetic gold nanostars (MGNs) and graphene quantum dots (GQDs). The MGNs binding anti-death receptors on cancer cell surfaces triggered by a magnetic field will aggregate, which will cause cancer cell death through promoting apoptosis signalling pathways. MGNs upon near-infrared (NIR) laser irradiation can exhibit excellent phtothermal conversion. GQDs have high drug (e.g. photosensitizer) loading capacity. Another drug loaded system contains B.bifidum, which can actively deliver drug to tumor with high efficiency, Upon the stimulations of both magnetic field and NIR laser irradiation, the growth of laryngeal tumor will be significantly inhibited by the two drug-loaded systems described above since they will exhibit a synergistic effect of biotherapy, photothermal and photodynamic therapies. The shortcomings of radiotherapy and chemotherapy may be overcome and the treatment technique of Laryngeal cancer may be improved by this strategy. .The method described in this project has more advantage such as safe, high efficiency, etc., compared with the traditional technique used in clinic. Great innovations can be found in these drug loaded structures and properties, as well as in the therapy strategy. The traditional laryngeal cancer therapy technique will be greatly improved by the achievements in this research project.

喉癌是头颈部常见的恶性肿瘤，放疗与化疗是其常用治疗手段。本项目在国际研究前沿和我们前期研究基础上，率先提出一种以静态磁场和近红外激光为载药粒子治疗喉癌的控制开关的全新策略，即：发挥磁性金纳米星不仅有很高光热转化效率、而且能在磁场遥控下通过快速诱导死亡受体聚集来诱导癌细胞凋亡的生物治疗优势，以及发挥已被证明可安全用于静脉注射的双歧杆菌能向肿瘤高效靶向送药的优越性、石墨烯量子点优异载药（如光敏剂）性能，构建可进行瘤中注射和静脉注射靶向送药配合应用的两种新型载药粒子，以静态磁场和近红外激光辐射肿瘤，诱导载药粒子在肿瘤中发挥"生物治疗 + 温热治疗 + 光动力治疗"的协同增效作用，高效摧毁肿瘤，克服临床放化治疗喉癌存在的不足，使喉癌治疗水平有新突破。.本项目具有安全、高效、靶向、方便、可控等巨大优势，在载药粒子构建和治疗策略上均有突出创新，研究成果对于促进喉癌治疗技术向更高层次发展，意义重大。

本项目研发了两种用于喉癌治疗的载药粒子，一种是在磁性氧化铁表面包覆金壳，形成星状结构，称之为磁性金纳米星（Fe3O4/Au nanostars），并连接石墨烯量子点（GQDs），装载光敏剂二氢卟吩e6（Ce6），连接抗癌细胞死亡受体5的抗体（anti-DR5 Ab），获得的载药粒子（(GQDs-Ce6)-Fe3O4/Au nanostars-(anti-DR5 Ab)）在静态磁场作用下，能通过磁性粒子聚集诱导癌细胞死亡受体聚集，进而诱导细胞凋亡；在671-nm激光照射下，这种载药粒子还产生光热效应和活性氧；在静态磁场和激光共同作用下，这种载药粒子通过光热治疗、光动力治疗和死亡受体5聚集的生物治疗共同杀伤喉癌细胞，瘤中直接注射这种载药粒子，在激光和磁场作用下能显著抑制小鼠喉癌肿瘤生长。另一种载药粒子是以两歧双歧杆菌（B.bifidum）为载体，装载Ce6，连接anti-DR5 Ab，获得的载药粒子（Ce6-B. bifidum-(anti-DR5 Ab)）通过荷瘤小鼠尾静脉注射后，能将Ce6靶向输送到小鼠喉癌肿瘤中，在671-nm激光照射下能显著抑制喉癌肿瘤生长。上述两种载药粒子和两种给药方式共同用于喉癌小鼠治疗，能更高效地抑制肿瘤生长。所合成的Fe3O4/Au nanostars和GQDs以及培养的B.bifidum均有较好的生物相容性。