Abstract
AbstractNanomaterials hold promise for the treatment of human carcinomas but integrating multiple functions into a single drug carrier system remains challenging. Herein, an integrated therapeutic delivery system for human hepatocellular carcinoma (HCC) treatment is reported, which is based on rhodamine B (RhB) end‐labeled cationic poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) and hydrophobic poly(3‐azido‐2‐hydroxypropyl methacrylate) (PGMA‐N3) segments equipped with a covalently bound galactose. This biocompatible and safe platform RhB‐PDMAEMA25‐c‐PGMA50‐Gal micelles (Gal‐micelles) offers four advantages: (1) Galactose ligands enhance cellular uptake by targeting the asialoglycoprotein receptor (ASGPR) that is overexpressed on HCC cell lines surfaces; (2) RhB end‐labeling facilitates real‐time imaging for tracking both in vitro and in vivo; (3) the acidic tumor microenvironment protonates the carrier system for efficient drug release as well as gene transfection, (4) codelivery of anticancer drug doxorubicin (DOX) and B‐cell lymphoma 2 small interfering RNA (Bcl‐2 siRNA) works synergistically against tumor growth in both subcutaneous and orthotopic HCC bearing mouse models. This integrated therapeutic delivery system holds potential for future clinical HCC treatment.
Published Version
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