Hyaluronic acid and Arg-Gly-Asp peptide modified Graphene oxide with dual receptor-targeting function for cancer therapy

J Biomater Appl. 2017 Jul;32(1):54-65. doi: 10.1177/0885328217712110. Epub 2017 May 29.

Abstract

Graphene oxide (GO) modified with hyaluronic acid (HA) and Arg-gly-asp peptide (RGD) was designed as a dual-receptor targeting drug delivery system to enhance the specificity and efficiency of anticancer drug delivery. Firstly, GO-HA-RGD conjugate was characterized to reveal its structure and morphology. Whereafter, doxorubicin (Dox) as a model drug was loaded on GO-HA-RGD carrier, which displayed a high loading rate (72.9%, GO:Dox (w/w) = 1:1), pH-response and sustained drug release behavior. Cytotoxicity experiments showed that GO-HA-RGD possessed excellent biocompatibility towards SKOV-3 and HOSEpiC cells. Additionally, the GO-HA-RGD/Dox had a stronger cytotoxicity for SKOV-3 cells than either GO-HA/Dox (single receptor) or GO/Dox (no receptor). Moreover, celluar uptake studies illustrated that GO-HA-RGD conjugate could be effectively taken up by SKOV-3 cells via a synergic effect of CD44-HA and integrin-RGD mediated endocytosis. Hence, GO-HA-RGD nanocarrier is able to be a promising platform for targeted cancer therapeutic.

Keywords: Graphene oxide; RGD peptide; cancer therapeutic; dual-receptor; hyaluronic acid; synergic effect; targeting drug delivery system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Cell Line, Tumor
  • Delayed-Action Preparations / chemistry*
  • Delayed-Action Preparations / metabolism
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Drug Delivery Systems
  • Graphite / chemistry*
  • Graphite / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / analogs & derivatives*
  • Hyaluronic Acid / metabolism
  • Integrins / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Oligopeptides / chemistry*
  • Oligopeptides / metabolism
  • Oxides / chemistry
  • Oxides / metabolism

Substances

  • Antibiotics, Antineoplastic
  • CD44 protein, human
  • Delayed-Action Preparations
  • Hyaluronan Receptors
  • Integrins
  • Oligopeptides
  • Oxides
  • Graphite
  • arginyl-glycyl-aspartic acid
  • Doxorubicin
  • Hyaluronic Acid