A Smart Nanoassembly for Multistage Targeted Drug Delivery and Magnetic Resonance Imaging |
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Authors: | Zhenhua Li Kai Dong Sa Huang Enguo Ju Zhen Liu Meili Yin Jinsong Ren Xiaogang Qu |
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Affiliation: | 1. State Key Laboratory of Rare Earth Resources, Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China;2. University of Chinese Academy of Sciences, Beijing, China;3. Department of Radiology, The Second Hospital of Jilin University, Changchun, Jilin, China |
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Abstract: | Efficient delivery of DNA‐toxin anticancer drugs into nucleus of targeted tumor cells while simultaneously minimizing the side effects to normal tissue is a major challenge for cancer therapy. Herein, a multistage continuous targeting strategy based on magnetic mesoporous silica nanoparticles to overcome the challenge is demonstrated. At the initial‐stage, the magnetic nanoparticle is capable of efficiently accumulating in tumor tissue guided by magnet. Following by the magnetic targeting, the targeting ligand gets it right into the cancer cell by receptor‐mediated endocytosis. Accompanied by endocytosis into the lysosomes, the nanoparticle reverses its surface charge from negative to positive which leads to the separation of charge‐conversional polymer from the nanoparticle to re‐expose the nuclear‐targeting TAT peptide. Finally, TAT peptide facilitates the carriers to enter nucleus and the DNA‐toxin camptothecin can inhibit topoisomerase I to induce cell apoptosis. Furthermore, the nano‐drug delivery system can be simultaneously used as predominant contrast agents for magnetic resonance imaging. This proof of concept might open the door to a new generation of carrier materials in the fields of targeted drug transport platform for cancer theranostics. |
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Keywords: | multistage drug delivery magnetic resonance imaging nanoassembly |
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