Urchin-like magnetic nanoparticles loaded with type X collagen siRNA and Stattic to treat triple negative breast cancer under rotating magnetic field like an “enchanted micro-scalpel”

Magnetic nanoparticles effectively target drug delivery, contrast agents, biosensors, and more. Urchin-like magnetic nanoparticles (UMN) with abundant spike-like structures exhibit superior magneto-mechanical force to destroy tumor cells compared with other shapes of magnetic nanoparticles. However, when cell contents are released from tumor cells induced by magneto-mechanical force, they can act on surrounding tumor cells to facilitate tumor development. Therefore, multifunctional UMN is necessary. Interleukin-6 (IL-6) is an important inflammatory factor which is released after cell rupture, it can activate the STAT3 signaling pathway to promote tumor progression. Type X collagen (COL10A1) is a significant component of the extracellular matrix, ranking second among all aberrant genes in triple negative breast cancer (TNBC), and its knockdown can suppress tumorigenesis and metastasis. Here, we built a rotating magnetic field (RMF) platform, and a novel UMN using a straightforward solvothermal method was synthesized, which was much simpler than existing method. Stattic (STAT3 inhibitor) and COL10A1 siRNA were loaded onto the UMN@PEI to form UMNP/St/si. The RMF drove UMNP/St/si disrupted the cell membrane, promoted cell death. The inhibitory effects of UMNP/St/si under RMF on TNBC were verified both in vitro and in vivo. Furthermore, despite the increase in IL-6 due to cell rupture, IL-6/STAT3 signaling pathway was inhibited by Stattic, compensating for the deficiency of magneto-mechanical force. Moreover, the underlying mechanical mechanism of UMNP/St/si after exposure to RMF was also analyzed. It suggests that UMNP/St/si is a promising and effective strategy for TNBC treatment and provides valuable insights for treating other diseases as well.