Enzyme-triggered targeted lipopeptide carriers for anti-tumor drug delivery: The effect of hydrophobicity and secondary structures

Delivery of antitumor drugs to tumor cells by targeted drug carriers is a very effective way to improve the efficiency of chemotherapy. We designed four lipopeptide sequences that can be specifically degraded by MMP-7, namely GPLGLARGDS (GR), C8-GPLGLARGDS (C8-GR), C12-GPLGLARGDS (C12-GR) and C16-GPLGLARGDS (C16-GR), which consist of three segments, the first segment was the hydrophobic chain, the middle segment was the MMP-7 specific degradable GPLGLA and the end segment was cell targeting group RGDS. These lipopeptide carriers can release the antitumor drugs after degradation by MMP-7 action. Targeted release of hydrophobic antitumor drugs is achieved. Due to the different hydrophobicity of four lipopeptides and two antitumor drugs doxorubicin hydrochloride (DOX) and curcumin (CCM), carriers showed different encapsulation and release behaviors. This study demonstrates that enzyme-sensitive targeting lipopeptides have good biocompatibility and low toxicity, enabling the feasibility of efficient targeted drug delivery and offering the possibility of enzyme-sensitive targeting peptides in biomedical oncology therapy.