ECM-targeted cancer interventions: nanobiotechnological paradigms for imaging and therapy

The Extracellular Matrix (ECM) is an active component of the tumour microenvironment, which promotes tumour progression, metastasis, immune evasion, and therapeutic resistance. As a result of the pathological remodelling of the ECM in malignancy, the tissue has a novel tumour-specific signature, marked by altered composition, stiffness, and architecture that distinguishes it from normal tissue, where the ECM serves as a key, exploitable biomarker for cancer detection and intervention. Even though the importance of the ECM in the pathophysiology of cancer is well-established, the structural complexity of this biomarker has not been fully exploited in therapy. The recent advances in nanobiotechnology have provided unparalleled prospects of ECM-targeted oncologic interventions. This review critically evaluates pathological ECM remodelling in malignancy and its role in driving tumorigenesis. It examines state-of-the-art nanoimaging modalities for ECM biomarker detection, including quantum dots, gold nanoparticles, carbon nanotubes, and graphene-based biosensors. Furthermore, it details innovative therapeutic strategies such as ECM-specific drug delivery systems, enzyme-responsive nanocarriers, and nano-inhibitors targeting matrix metalloproteinases (MMPs) and lysyl oxidases (LOX). We also discuss nanotechnological approaches to modulate the ECM for enhancing immune cell infiltration and highlight the synergistic potential of combining ECM-targeted nanotherapeutics with immunotherapy and chemotherapy. Ultimately, this review highlights how integrating nanobiotechnology with matrix biology can revolutionize cancer diagnostics, theranostics, and therapy. By enabling highly specific delivery to the tumour stroma and tackling salient challenges of ECM heterogeneity, biosafety, and clinical translation, this paradigm shift from tumor-centric to matrix-centric interventions holds promise for the future of precision oncology.