A Smart Nanoassembly for Multistage Targeted Drug Delivery and Magnetic Resonance Imaging

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. A multistage continuous targeting strategy (targeting from tumor tissue, cancer cell to organelle) based on magnetic mesoporous silica nanoparticles, to achieve nucleus‐targeted drug delivery and cancer therapy while simultaneously minimizing the side effects to normal tissue, is demonstrated. In addition, this smart nanoassembly can be used as predominant contrast agents for magnetic resonance imaging.