Nanochemical modulation of ECM-driven pseudo-resistance: convergent microenvironmental pathways in COVID-19 and cancer

Abstract

Extracellular matrix (ECM) remodeling is increasingly recognized as a central determinant of inflammation, fibrosis, and therapeutic response across chronic diseases. This Perspective examines how post-COVID-19 pulmonary fibrosis and stromal-driven resistance in solid tumors converge on a shared phenomenon, ECM-driven pseudo-resistance, an extrinsic and reversible microenvironmental state in which pathological matrix architecture, fibro-inflammatory signaling, and immune exclusion transiently limit therapeutic efficacy without conferring stable, mutation-driven cellular resistance. We highlight how nanochemical strategies, including ECM-penetrating and ECM-modulating nanohybrids, can dismantle these physical and signaling barriers by reprogramming matrix stiffness, mechanotransduction, and immune accessibility. By integrating evidence from virology, oncology, and materials science, this review proposes that targeting conserved ECM pathways through advanced nanochemistry offers a cross-disease therapeutic paradigm for overcoming pseudo-resistance in fibrotic and malignant pathologies.