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Multifunctional nanoparticles for targeting liver cancer stem cells and efficient endocytosis

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Initiation and progression of liver cancer are driven by a subpopulation of tumor cells—the cancer stem cells (CSCs). Thus, targeted therapy of CSCs holds great promise for providing important new impetus to tumor biology and clinical oncology. CD133 is one of the important surface markers of liver CSCs. Cell-penetrating peptide (CPP) is defined as the peptide sequence capable of transporting various molecules efficiently into cells across membranes. In this study, paclitaxel-loaded nanoparticles (NPs) are modified with anti-CD133 antibody and CPP (Polyarginine) to construct multifunctional drug delivery system for targeting liver CSCs and efficient endocytosis. NPs were prepared by emulsification–solvent evaporation method and modified by carbodiimide hydrochloride and hydroxysuccinimide (EDC/NHS). The physicochemical characteristics of NPs (i.e., encapsulation efficiency, particle size distribution, morphology, release in vitro) were determined. Cellular uptake of NPs was investigated. Using the hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh7), cell survival assay was performed to assess anti-tumor activity in vitro of NPs. Particle size distribution of NPs was between 50 and 200 nm. Drug-loaded NPs showed spherical morphology and higher encapsulation efficiency. The release behavior of paclitaxel from the polymer NPs showed an immediate burst effect. The accumulation of NPs modified with the ligands depended on passive and active targeting. Drug-loaded NPs caused cytotoxicity on HepG2 and Huh7 cells. NPs modified with both ligands maximized the selectivity and therapeutic effect for liver CSCs. This study provided a new idea for HCC therapy in the future.

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This work was funded by Xi'an Health Commission Project (No. J201903071).

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Correspondence to Cheng Jin.

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Jin, C., Bai, L. & Wang, S. Multifunctional nanoparticles for targeting liver cancer stem cells and efficient endocytosis. Chem. Pap. 77, 1395–1403 (2023).

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