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Design of an intelligent sub-50 nm nuclear-targeting nanotheranostic system for imaging guided intranuclear
Wenpei Fan1, Bo Shen2, Wenbo Bu1
1State Key Laboratory of High Performance Ceramics and Superfine Microstructures , Shanghai Institute of Ceramics , Chinese Academy of Sciences , Shanghai , 200050 , P. R. China . Email: wbbu@mail.sic.ac.cn ;
Abstract:
Clinically applied chemotherapy and radiotherapy is sometimes not effective due to the limited dose acting on DNA chains resident in the nuclei of cancerous cells. Herein, we develop a new theranostic technique of "intranuclear radiosensitization" aimed at directly damaging the DNA within the nucleus by a remarkable synergetic chemo-/radiotherapeutic effect based on intranuclear chemodrug-sensitized radiation enhancement. To achieve this goal, a sub-50 nm nuclear-targeting rattle-structured upconversion core/mesoporous silica nanotheranostic system was firstly constructed to directly transport the radiosensitizing drug Mitomycin C (MMC) into the nucleus for substantially enhanced synergetic chemo-/radiotherapy and simultaneous magnetic/upconversion luminescent (MR/UCL) bimodal imaging, which can lead to efficient cancer treatment as well as multi-drug resistance circumvention in vitro and in vivo. We hope the technique of intranuclear radiosensitization along with the design of nuclear-targeting nanotheranostics will contribute greatly to the development of cancer theranostics as well as to the improvement of the overall therapeutic effectiveness.
