PMID- 33003260 OWN - NLM STAT- MEDLINE DCOM- 20210310 LR - 20210310 IS - 1944-8252 (Electronic) IS - 1944-8244 (Linking) VI - 12 IP - 39 DP - 2020 Sep 30 TI - Low-Dose X-ray-Responsive Diselenide Nanocarriers for Effective Delivery of Anticancer Agents. PG - 43398-43407 LID - 10.1021/acsami.0c11627 [doi] AB - X-ray-responsive nanocarriers for anticancer drug delivery have shown great promise for enhancing the efficacy of chemoradiotherapy. A critical challenge remains for development of such radiation-controlled drug delivery systems (DDSs), which is to minimize the required X-ray dose for triggering the cargo release. Herein, we design and fabricate an effective DDS based on diselenide block copolymers (as nanocarrier), which can be triggered to release their cargo with a reduced radiation dose of 2 Gy due to their sensitivity to both X-ray and the high level of reactive oxygen species (ROS) in the microenvironment of cancer cells. The underlying molecular mechanism is further illustrated by proton nuclear magnetic resonance ((1)H NMR) experiments and density functional theory (DFT) calculations. In vivo experiments on tumor-bearing mice validated that the loaded drugs are effectively delivered to the tumor site and exert remarkable antitumor effects (minimum tumor volume/weight) along with X-ray. Furthermore, the diselenide nanocarriers exhibit no noticeable cytotoxicity. These findings provide new insights for the de novo design of radiation-controlled DDSs for cancer chemoradiotherapy. FAU - Zhang, Lianxue AU - Zhang L AD - State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. FAU - Zhang, Shitong AU - Zhang S AD - State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. FAU - Xu, Jiaying AU - Xu J AD - State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. FAU - Li, Youyun AU - Li Y AD - State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. FAU - He, Jinlin AU - He J AUID- ORCID: 0000-0003-3533-2905 AD - College of Chemistry, Chemical Engineering and Materials Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, Suzhou 215123, China. FAU - Yang, Ying AU - Yang Y AD - State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. FAU - Huynh, Tien AU - Huynh T AD - Computational Biology Center, IBM Thomas J Watson Research Center, Yorktown Heights, New York 10598, United States. FAU - Ni, Peihong AU - Ni P AUID- ORCID: 0000-0003-4572-3213 AD - College of Chemistry, Chemical Engineering and Materials Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, Suzhou 215123, China. FAU - Duan, Guangxin AU - Duan G AD - State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. FAU - Yang, Zaixing AU - Yang Z AUID- ORCID: 0000-0003-3521-6867 AD - State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. FAU - Zhou, Ruhong AU - Zhou R AUID- ORCID: 0000-0001-8624-5591 AD - State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. AD - Computational Biology Center, IBM Thomas J Watson Research Center, Yorktown Heights, New York 10598, United States. AD - Department of Chemistry, Columbia University, New York, New York 10027, United States. LA - eng PT - Journal Article DEP - 20200807 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Drug Carriers) RN - 0 (Selenium Compounds) RN - 80168379AG (Doxorubicin) SB - IM MH - Animals MH - Antibiotics, Antineoplastic/chemical synthesis/chemistry/*pharmacology MH - Breast Neoplasms/diagnostic imaging/drug therapy MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Density Functional Theory MH - Doxorubicin/chemical synthesis/chemistry/*pharmacology MH - Drug Carriers/chemical synthesis/chemistry MH - *Drug Delivery Systems MH - Drug Screening Assays, Antitumor MH - Humans MH - Mice MH - Optical Imaging MH - Particle Size MH - Selenium Compounds/chemical synthesis/*chemistry MH - Surface Properties MH - X-Rays OTO - NOTNLM OT - X-ray-responsive drug delivery system OT - cancer therapy OT - density functional theory calculations OT - diselenide nanocarriers OT - reactive oxygen species EDAT- 2020/10/03 06:00 MHDA- 2021/03/11 06:00 CRDT- 2020/10/02 01:00 PHST- 2020/10/02 01:00 [entrez] PHST- 2020/10/03 06:00 [pubmed] PHST- 2021/03/11 06:00 [medline] AID - 10.1021/acsami.0c11627 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2020 Sep 30;12(39):43398-43407. doi: 10.1021/acsami.0c11627. Epub 2020 Aug 7.