Tumor microenvironment expressed enzymes (Matrix metalloproteinases, cathepsins, urokinase-type plasminogen activator) triggered polymersomes for liquid biopsy and cancer diagnostics: A review.
Journal:
International journal of biological macromolecules
Published Date:
Jul 28, 2025
Abstract
Enzyme-triggered polymersomes have emerged as a transformative platform in liquid biopsy and cancer diagnostics, enabling high-accuracy biomarker detection through precise enzymatic responsiveness. This review comprehensively examines the rational design, synthesis, and functionalization strategies of enzyme-responsive polymersomes, which undergo programmed structural changes in the presence of tumor microenvironment-associated enzymes such as matrix metalloproteinases (MMPs), cathepsins, and urokinase-type plasminogen activator (uPA). Key advances in polymer chemistry, including block copolymer self-assembly, stimuli-responsive linker integration, and surface ligand conjugation, have been critical in tailoring polymer specificity, enzymatic sensitivity, and biocompatibility. These engineered nanocarriers exploit the overexpression of tumor-associated proteases and lipases to selectively release DNA stains, fluorescent probes, contrast agents, and molecular barcodes, facilitating ultrasensitive detection of circulating tumor cells (CTCs), extracellular vesicles (EVs), and cell-free nucleic acids (cfNAs) in liquid biopsies. Recent innovations in enzyme-triggered cargo release mechanisms, CRISPR-integrated biosensing, and machine learning-enhanced biomarker analysis have further amplified diagnostic precision. Additionally, multifunctional polymersomes bridge diagnostics and therapy, serving as potent theranostic agents. By integrating advanced material synthesis with enzymatic targeting, these systems offer minimally invasive, real-time monitoring and personalized cancer detection. This review highlights current breakthroughs and future directions in enzyme-responsive nanotechnology, underscoring its potential to revolutionize precision oncology.
