Spatiotemporally Controlled Formation and Rotation of Magnetic Nanochain In Vivo for Precise Mechanotherapy of Tumor.

Systemic cancer therapy is always accompanied with toxicity to normal tissues, which prompts concerted efforts to develop precise cancer therapy strategy. Herein, we firstly develop an intriguing approach that enables spatiotemporally controlled formation and rotation of magnetic nanochains in vivo, allowing for precise mechanotherapy of tumor with minimal side effects. The building blocks of the nanochain are hybrid nanocomposites of pheophorbide-A (PP) modified iron oxide nanoparticles (IONPs) and lanthanide-doped down-conversion nanoparticles (DCNPs). By applying permanent magnetic field, the nanocomposites would be aligned to form nanochain. Next, MnO 2 NPs were subsequently administrated to accumulate in tumors as supplier of Mn 2+ , which effectively coordinates with the PP located at the joint the nanocomposite to immobilize the formed nanochains. In rotating magnetic field, the nanochains would rapidly rotate, leading to mechanical damage to organelles and cytoskeletons, and consequently resulting in apoptosis/necrosis of tumor cells. Furthermore, the IONPs and DCNPs showed high T 2 -MR and NIR-II fluorescence imaging performances, respectively, which systematically facilitate to determine the tumor location and guide therapy. Overall, we represent a novel mechanotherapy strategy with great potential in practical applications.