Cell membrane-camouflaged chemotactic nanomotors for enhanced cancer chemotherapy

Enhancing tumor targeting, intratumoral penetration, and cellular internalization is critical for drug delivery systems to tackle the challenges on limited therapeutic efficacy. Herein, we report an enzyme-powered, cancer cell membrane-camouflaged mesoporous silica (GC-CM@MSN) nanomotor with a simple fabrication process and enhanced performance as a self-propelled nanocarrier. The GC-CM@MSN nanomotors consist of mesoporous silica nanoparticles camouflaged with the 4T1 cell membrane, on which glucose oxidase (GOx) and catalase are unevenly immobilized. The nanomotors exhibit self-propulsion and positive chemotaxis in response to the concentration gradients of glucose, pH, or their combination. By integrating homologous targeting, enhanced mobility, and chemotactic navigation, GC-CM@MSN nanomotors achieve efficient cellular uptake, deep intratumoral penetration, and high tumor accumulation. In vivo studies confirm the significantly superior antitumor efficacy of GC-CM@MSN nanomotors over passive delivery systems. The straightforward integration of the chemotaxis motion of enzyme-powered nanomotors with the cell membrane-camouflaged technology represents a promising strategy for deep tumor penetration and accumulation. This study provides valuable insights into the applications of nanomotors for actively targeted cancer drug delivery.