Enzymatic nanomotors with chemotaxis for product-based cancer therapy

The development of an intelligent nanomotor system holds great promise for enhancing the efficiency and effectiveness of antitumor therapy. Leveraging the overexpressed substances in the tumor microenvironment as propellants and chemotactic factors for enzyme-powered nanomotors represents a versatile and compelling approach. Herein, a plasma amine oxidase (PAO)-based chemotactic nanomotor system has been successfully developed, with the ability to enzymatically produce toxic acrolein and H2O2 from the upregulated polyamines (PAs) in the tumor microenvironment for active tumor therapy. Zwitterionic polymeric nanoparticles with superior biocompatibility are synthesized, followed by PAO modification via electrostatic interactions. As expected, the resulting nanomotor system exhibits positive chemotaxis toward PAs concentration gradient. Upon reaching the tumor region, our nanomotors, actuated by the tumor microenvironmental PAs, effectively enhance diffusion and enable deep penetration into the tumor site. This leads to the induction of tumor apoptosis and simultaneous inhibition of tumor invasion and migration by decomposing PAs into toxic products. By smartly utilizing the consumption of these local chemotactic factors and their enzymatic products, our nanomotor system provides a versatile and intelligent platform for active and enhanced tumor therapy. Chemotactic nanomotor shows intelligent positive chemotaxis toward tumor microenvironmental polyamines concentration gradient and enzymatically produces toxic acrolein and H2O2 for product-based cancer therapy. [Display omitted] •Nanomotor effectively enhances the diffusion and enables deep penetration into the tumor cells by enzymatic reaction.•Enzymatic nanomotor induces tumor cell apoptosis by in situ decomposing tumorpolyamines into toxic products•Nanomotor exhibits positive chemotaxis toward polyamines concentration gradient.