Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, Republic of Korea.
Division of Cancer Biology, Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, Republic of Korea.
J Control Release. 2020 Sep 10;325:100-110. doi: 10.1016/j.jconrel.2020.06.025. Epub 2020 Jul 1.
Radiotherapy (RT) is a major modality for cancer treatment, along with surgery and chemotherapy. Despite its therapeutic effect, the recurrence and metastasis of tumors due to the acquired resistance of cancer cells to RT remain significant clinical problems. Therefore, it is imperative to overcome radioresistance and improve radiosensitivity in cancer patients. Here, we synthesized hydroxychloroquine (HCQ)-loaded hollow mesoporous silica nanoparticles (HMSNs) to enable effective inhibition of radiation-induced cytoprotective autophagy and enhance the therapeutic efficacy of RT. HCQ-HMSN-treated HCT116 colon cancer cells showed a 200-fold higher intracellular uptake of HCQ than that of free HCQ-treated cells, thereby effectively inhibiting the radiation-induced autophagy of cancer cells. In vivo imaging and therapy studies of a tumor xenograft model showed preferential accumulation of HCQ-HMSNs in tumor tissues and significant enhancement of RT by inhibiting autophagy in the tumor sites. Histopathology analyses of major organs, blood chemistry profiles, and changes in body weights of mice confirmed the good biocompatibility of HCQ-HMSNs.
放射治疗（RT）是癌症治疗的主要手段之一，与手术和化疗并列。尽管 RT 具有治疗效果，但由于癌细胞对 RT 的获得性耐药性，肿瘤的复发和转移仍然是重大的临床问题。因此，克服肿瘤的放射抗性并提高癌症患者的放射敏感性迫在眉睫。在这里，我们合成了载有羟氯喹（HCQ）的中空介孔硅纳米粒子（HMSNs），以有效抑制辐射诱导的细胞保护性自噬，并增强 RT 的治疗效果。与游离 HCQ 处理的细胞相比，HCQ-HMSN 处理的 HCT116 结肠癌细胞对 HCQ 的细胞内摄取增加了 200 倍，从而有效地抑制了癌细胞的辐射诱导自噬。肿瘤异种移植模型的体内成像和治疗研究表明，HCQ-HMSNs 在肿瘤组织中优先积累，并通过抑制肿瘤部位的自噬显著增强 RT。对主要器官的组织病理学分析、血液化学特征以及小鼠体重变化的检测证实了 HCQ-HMSNs 的良好生物相容性。
