국립암센터 / 리안, 정희선*, 최용두*
Abstract
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.
그림. 히드록시 클로로퀸이 탑재된 중공다공성 실리카나노입자를 방사선 치료전 정맥투여 함으로써, 방사선 치료시 암세포에서 일어나는 오토파지를 효과적으로 억제하고 방사선 치료효과를 향상시킬 수 있음.
Affiliations
Yan Li 1 , Mi Hyeon Cho 1 , Seon Sook Lee 1 , Dong-Eun Lee 2 , Heesun Cheong 3 , Yongdoo Choi 4
1 Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, Republic of Korea.
2 Division of Cancer Biology, Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, Republic of Korea.
3 Division of Cancer Biology, Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, Republic of Korea. Electronic address: heesunch@ncc.re.kr.
4 Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, Republic of Korea. Electronic address: ydchoi@ncc.re.kr.