Microenvironment-driven transformable self-assembly nanoplatform enables spatiotemporal remodeling for rheumatoid arthritis therapy.

The aberrant vasculature within the inflamed joint cavity of rheumatoid arthritis (RA) not only exacerbates joint pathology but also restricts the effective delivery of therapeutic drugs. Herein, we propose a strategy that involves the rapid and sustained vasculature repair alongside microenvironment-driven drug delivery to achieve multifaceted RA management. The transformable, self-assembling nanoplatform specifically accumulates in the inflamed joint cavity guided by a vascular targeting peptide (STP). Subsequently, STP detaches and undergoes shape transformation, forming nanofibers on the vascular endothelium, which serve as a rapid-acting physical barrier in the short term and facilitate sustained vascular normalization in the long term. Concurrently, the remaining nanoparticles undergo charge reversal and RGD exposure, enabling precise delivery of anti-RA agent triptolide and the immunomodulatory agent metformin. Collectively, this study provides a potent strategy for rapid, sustained, and precise spatiotemporal remodeling of RA using a simple yet intelligent self-assembling nanoplatform.