Hyaluronic acid-shelled, peptide drug conjugate-cored nanomedicine for the treatment of hepatocellular carcinoma
2020
Abstract Peptide-drug conjugate (PDC) is a promising prodrug in drug delivery systems. To fabricate nanostructures with proper molecular design which can self-assemble to spherical morphologies is very important for PDC chemotherapy. In this study, a novel PDC (PDC-DOX2), in which two doxorubicin (DOX) molecules are conjugated onto a short peptide (KIGLFRWR) with self-assembly function, was designed and synthesized. PDC-DOX2 with self-assembly properties forms a spherical structure under hydrophobic interaction in water. Hyaluronic acid (HA) was then coated on PDC-DOX2 micelles to form a HA-shelled, peptide-doxorubicin conjugate-cored nanomedicine (HA@PDC-DOX2). The amount of HA can regulate the particle size and stabilization of HA@PDC-DOX2. In addition, HA can actively enhance the targeting effects of PDC-DOX2 micelles since it can interact with overexpressed receptors in cancer cells. The core-shell structured HA@PDC-DOX2 nanomedicine showed significantly enhanced potency against hepatocellular carcinoma compared to PDC-DOX2 micelles as well as free DOX. In this work, a novel PDC which can self-assemble to spherical morphologies and a core-shell structure HA@PDC-DOX2 nanomedicine are designed and prepared. It provides a convenient strategy for the size control of PDC assemblies and constructs effective PDC-based drug delivery systems for cancer treatment.
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