Multifunctional Janus Nanoparticles Capable of Anchoring to the Cell Membrane and Serving as “Cellular Backpacks” for Advanced Theranostics

A cell-based theranostic system can be fabricated by attaching nanomedicines to the surface of carrier cells, but it remains a challenge to achieve the attachment without involving endocytosis. Herein, we address this challenge by developing multifunctional Janus nanoparticles with orthogonal surface properties for the two opposite halves. When incubated with carrier cells, the hydrophobic half made of polystyrene readily inserts into the plasma membrane, whereas the hydrophilic SiO₂ half grafted with poly(ethylene glycol) protrudes away from the cell surface. Additionally, the SiO₂ half can be made with a cavity to hold theranostic agents and thus serves as a "backpack" for the carrier cell. By confining the theranostic agents in the SiO₂ compartment and outside the carrier cell during the delivery process, their adverse impact on the cell is minimized. Upon release in an in vitro spheroid model, the agents quickly eradicate cancer cells. Moreover, the polystyrene half can be loaded with superparamagnetic nanoparticles to enhance magnetic resonance imaging contrast and enable magnetic manipulation, facilitating image-guided and target-directed treatments. By further optimizing the interactions between the multifunctional Janus nanoparticles and carrier cells, this system can be developed into a robust platform for cell-based theranostics.