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Nanochemical modulation of ECM-driven pseudo-resistance: convergent microenvironmental pathways in COVID-19 and cancer
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DOI：10.1039/D5CC07234D.png)
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Abstract
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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.
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