Pressure‐Gradient Counterwork of Dual‐Fuel Driven Nanocarriers in Abnormal Interstitial Fluids for Enhancing Drug Delivery Efficiency

Abstract The abnormal pressure in tumor tissue is a significant limitation on the drug delivery efficiency of tumor therapy. This work reports a gradient‐driven nanomotor as drug nanocarrier with the pressure‐counterworking function. The dual‐fuel nanomotors are formed by co‐electrospinning of the photosensitive polymers with calcium peroxide (CaO₂) and catalase (CAT), followed by ultraviolet (UV) irradiation and bovine serum albumin (BSA) incubation. The UV‐responsive cleavage nanomotors can effectively release O₂ molecules at the fractures as a driving force to increase the delivery speed and escape the phagocytosis of macrophage system in normal tissues. Furthermore, CAT catalyzes H₂O₂ produced by CaO₂ and the tumor interstitial fluids to provide stronger power for the nanomotors. Additionally, according to the analysis of directional motions of the nanomotors, the functional relationship between the rotational diffusion coefficient (D_R) and the physiological viscosity is constructed. The dual‐fuel nanocarriers enable up to 13.25% of the injected dose (ID)/per gram tissue and significantly improve the penetration in deep tumor. It is of vital importance to design and obtain the adaptive pressure‐gradient counterworking nanomotors, which can effectively improve the drug delivery efficiency in vitro and in vivo.