Biomedical Multidisciplinary Innovation Research Institute and Research Center for Translational Medicine at Shanghai East Hospital, School of Life Sciences and Technology , Tongji University , Shanghai 200092 , P. R. China.
Institute of Biophysics , Chinese Academy of Science , Beijing 100101 , P. R. China.
ACS Appl Mater Interfaces. 2018 Sep 19;10(37):31186-31197. doi: 10.1021/acsami.8b11748. Epub 2018 Sep 10.
Graphitic carbon nanocages (GCNCs) have unique geometric structures and physical properties, which have been extensively investigated for various applications. However, no reports focusing on using GCNCs and polymer-coated GCNCs for solid tumor ablation induced by near-infrared laser irradiation under enhanced initial body temperature, or on the biosafety of GCNCs in vivo, have been published. Here, we developed chitosan (CS)-coated GCNCs and showed that both GCNCs and GCNCs/CS in mouse tumors can rapidly convert an 808 nm laser light energy into heat, which efficiently kill nasopharyngeal carcinoma cells and inhibit tumor growth. The tumors are further damaged by the phototoxicity of GCNCs/CS after loading with 5-Fluorouracil (5FU). Tumors are no longer detected after 6 days of 5FU-GCNCs/CS treatment under irradiation, which is due to the synergistic effect of the photothermal response of GCNCs and the chemotherapy of 5FU. None of the tumors reappeared during the following 12 days of no irradiation. Interestingly, increasing the initial body temperature of the mice significantly improved the photothermal effect of GCNCs in vivo and the synergistic effect of photothermal therapy and chemotherapy, thus accelerating the shrinking of tumors. To the best of our knowledge, this is the first study to improve the photothermal ablation of GCNCs and synergetic photothermal-chemotherapy of drug-loaded GCNCs through enhancing the initial body temperature. As the results show that GCNCs, GCNCs/CS, and 5FU-GCNCs/CS are safe in mice after intratumoral injection both with and without laser irradiation, our technique may have great potential for future clinical translation.
石墨碳纳米笼(GCNCs)具有独特的几何结构和物理性质,已被广泛研究用于各种应用。然而,目前尚无报道专门研究使用 GCNCs 和聚合物包覆的 GCNCs 在增强初始体温下通过近红外激光照射诱导实体瘤消融,以及 GCNCs 在体内的生物安全性。在这里,我们开发了壳聚糖(CS)包覆的 GCNCs,并表明 GCNCs 和 GCNCs/CS 在小鼠肿瘤中均能迅速将 808nm 激光能量转化为热能,有效杀死鼻咽癌细胞并抑制肿瘤生长。载有 5-氟尿嘧啶(5FU)后,GCNCs/CS 的光毒性进一步破坏肿瘤。在照射下,用 5FU-GCNCs/CS 治疗 6 天后,肿瘤不再被检测到,这是由于 GCNCs 的光热响应和 5FU 的化学疗法的协同作用。在接下来的 12 天没有照射的情况下,没有一个肿瘤再次出现。有趣的是,提高小鼠的初始体温显著提高了 GCNCs 在体内的光热效应以及光热治疗和化学疗法的协同作用,从而加速了肿瘤的缩小。据我们所知,这是首次通过提高初始体温来改善 GCNCs 的光热消融和载药 GCNCs 的协同光热化疗的研究。由于结果表明 GCNCs、GCNCs/CS 和 5FU-GCNCs/CS 在肿瘤内注射后无论是否进行激光照射,在小鼠体内都是安全的,因此我们的技术可能具有很大的临床转化潜力。