Multistage microrobots with pH-responsive release of platelet membrane-coated nanoparticles.

Abstract

Targeted drug delivery in the gastrointestinal tract remains challenging because therapeutics must overcome multiple hierarchical barriers before reaching diseased tissue. Here, we present a multistage delivery platform that integrates magnetic microrobots, a pH-responsive protective coating, and platelet membrane-coated nanoparticles (PNPs) in one platform. A fillable design enables the formation of an internal magnetic layer for microrobot actuation, while the pH-responsive coating protects the cargo during transit and selectively degrades upon pH change, releasing cancer cell-targeting PNPs. In an in vitro colon cancer model that reproduces key gastrointestinal features, including flow, pH variation, and villi-like structures, this strategy increased nanoparticle retention and enhanced cancer cell cytotoxicity compared to nanoparticles administered alone. Ex vivo studies in porcine stomach and intestine further demonstrated robust locomotion on compliant and folded tissue surfaces. These results establish an environment-responsive hierarchical delivery strategy for more precise oral delivery in complex gastrointestinal settings.