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To solve biostability and organ distribution problems in polymer-coated liposomes, this study developed tumor−extracellular matrix pH-induced targeting polymer− liposome complexes (ECM-targeting liposomes) that are highly stable in a protein-rich environment and can trigger targeting ability in tumor ECM environment. Experimental results show that the ECM-targeting liposomes significantly reduced adsorption of various proteins (HSA, IgG, and fibrinogen) and leakage of encapsulated drug doxorubicin− hydrochloride from liposomes, significantly improved uptake efficiency in HCT116 colon cancer cells, improved HCT116 tumor accumulation, and reduced distribution in normal organs (e.g., liver, spleen, lung, etc.). We demonstrate that ECM-targeting liposomes overcome the limitations of conventional liposomes and stealth liposomes in cancer therapy.

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