Hyaluronic acid-serum albumin conjugate-based nanoparticles for targeted cancer therapy

Ravit Edelman, Yehuda G. Assaraf, Inna Levitzky, Tal Shahar, Yoav D. Livney

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Multiple carcinomas including breast, ovarian, colon, lung and stomach cancer, overexpress the hyaluronic acid (HA) receptor, CD44. Overexpression of CD44 contributes to key cancer processes including tumor invasion, metastasis, recurrence, and chemoresistance. Herein, we devised novel targeted nanoparticles (NPs) for delivery of anticancer chemotherapeutics, comprised of self-assembling Maillard reaction-based conjugates of HA and bovine serum albumin (BSA). HA served as the hydrophilic block, and as the ligand for actively targeting cancer cells overexpressing CD44. We demonstrate that Maillard reaction-based covalent conjugates of BSA-HA self-assemble into NPs, which efficiently entrap hydrophobic cytotoxic drugs including paclitaxel and imidazoacridinones. Furthermore, BSA-HA conjugates stabilized paclitaxel and prevented its aggregation and crystallization. The diameter of the NPs was < 15 nm, thus enabling CD44 receptor-mediated endocytosis. These NPs were selectively internalized by ovarian cancer cells overexpressing CD44, but not by cognate cells lacking this HA receptor. Moreover, free HA abolished the endocytosis of drug-loaded BSA-HA conjugates. Consistently, drug-loaded NPs were markedly more cytotoxic to cancer cells overexpressing CD44 than to cells lacking CD44, due to selective internalization, which could be competitively inhibited by excess free HA. Finally, a CD44-targeted antibody which blocks receptor activity, abolished internalization of drug-loaded NPs. In conclusion, a novel cytotoxic drug-loaded nanomedicine platform has been developed, which is based on natural biocompatible biopolymers, capabale of targeting cancer cells with functional surface expression of CD44.

Original languageEnglish
Pages (from-to)24337-24353
Number of pages17
JournalOncotarget
Volume8
Issue number15
DOIs
StatePublished - 1 Jan 2017
Externally publishedYes

Keywords

  • Cancer
  • Hyaluronic acid
  • Maillard reaction
  • Nanovehicles
  • Targeted therapy

Fingerprint

Dive into the research topics of 'Hyaluronic acid-serum albumin conjugate-based nanoparticles for targeted cancer therapy'. Together they form a unique fingerprint.

Cite this