Hyaluronic acid-shelled, peptide drug conjugate-cored nanomedicine for the treatment of hepatocellular carcinoma

• Published in: Materials Science & Engineering C Vol. 117; p. 111261
• Main Authors: Wang, Jingjing, Qian, Ying, Xu, Liu, Shao, Yurou, Zhang, Hu, Shi, Fanli, Chen, Jiaxin, Cui, Siqi, Chen, Xiaoyan, Zhu, Dongwei, Hu, Rongfeng, Chen, Zhipeng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2020; Elsevier BV
• Subjects: Cancer; Carcinoma, Hepatocellular - drug therapy; Chemotherapy; Conjugates; Core-shell structure; Doxorubicin; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug delivery; Drug Delivery Systems; Drug development; Hepatocellular carcinoma; Humans; Hyaluronic acid; Hyaluronic Acid - therapeutic use; Hydrophobicity; Liver cancer; Liver Neoplasms - drug therapy; Materials science; Micelles; Morphology; Nanomedicine; Nanotechnology; Peptide drug conjugate; Peptides; Peptides - therapeutic use; Self-assembly; Stability; System effectiveness; Peptide drug conjugate; Self-assembly; Stability; Hyaluronic acid; Nanomedicine
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2020.111261

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.
•A novel PDC which can self-assemble to spherical morphologies is designed.•It provides a convenient strategy for the size control of PDC assemblies.•It constructs effective PDC-based drug delivery systems for cancer treatment.