Programmable Morphology‐Adaptive Peptide Nanoassembly for Enhanced Catalytic Therapy

Abstract Nanocatalytic therapy holds significant promise in cancer treatment by exploiting the high oxidative stress within tumor cells. However, efficiently delivering nanocatalytic agents to tumor tissues and maximizing their catalytic activity in situ remain critical challenges. Morphology‐adaptive delivery systems, capable of adjusting their physical form in response to physiological conditions, offer unique spatiotemporal control for navigating complex biological environments like the tumor microenvironment. While designing systems that undergo multiple shape transformations often involves complex stimuli‐responsive mechanisms, making programmable responses through simple designs highly desirable yet challenging. Here, FeFKC, an innovative adaptive material is introduced that achieves multi‐step morphological transformations at the tissue level and amplifies catalytic activity through a straightforward design. As the microenvironmental pH decreases during drug delivery, FeFKC dynamically transitions between single chains, nanoparticles, and nanofibers. This programmable shape‐shifting facilitates deep tumor penetration, enhanced cellular uptake, and lysosomal escape, significantly improving its catalytic efficiency in nanocatalytic tumor therapy. In vivo studies demonstrate that FeFKC achieves impressive tumor suppression efficacy of up to 95% without notable biosafety concerns. The findings highlight the potential of adaptive nanomaterials with programmable shape‐transforming capabilities to overcome biological barriers and enhance catalytic therapy, opening new avenues for cancer treatment and other complex diseases.