Left: Primary tumor or overt metastasis Center: Center: Pre-metastatic niche Right: Post-surgical wound
CREDIT: 2021 Innovation Center of NanoMedicine
- Matrix metalloproteinases (MMPs) is an enzyme required for cancer cells to metastasize/invade, and cancer cells with higher MMP activity have higher metastasis ability and progress quickly.
In this study, we created polymersomes (smart nanomachines) that act specifically in tissues that overproduce MMPs, prevent cancer metastasis, and developed a method to remove residual tumor tissue that could not be visually confirmed after surgery.
- We simultaneously loaded the cell division inhibitor colchicine and the MMP inhibitor marimastat into MMPs-responsive polymersomes as an enzymatically transformable nanomachine designed to achieve transformation following dePEGylation by cleavage of the inserted substrate peptide by MMPs. The effect on malignant tumors with high MMPs activity was evaluated.
- During transformation, nanomachines with exposed guanidine residues easily penetrate into cells, and at the same time, by releasing the contained drugs, it exerts an anti-cancer effect.
- Evaluating drug uptake using HT1080 cells derived from human fibrosarcoma that overproduce MMPs, studying pharmacokinetic and nano-bio interaction using a confocal laser scanning biomicroscope and evaluating metastasis inhibitory effect using triple-negative breast cancer transplantation model, the results were published in Advanced Materials (IF = 30.849 in 2021).
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