PEGylated Nanographene Oxide for Delivery of Water-Insoluble Cancer Drugs

TLDR

It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. The study aims to functionalize nanographene oxide with branched PEG to create a biocompatible, stable conjugate that can noncovalently attach hydrophobic aromatic drugs such as SN38 via π–π stacking. NGO was PEGylated and then loaded with SN38 by π–π stacking, yielding a water‑soluble complex. The NGO–PEG–SN38 complex showed excellent water solubility and retained high cancer‑cell‑killing potency comparable to free SN38, outperforming the FDA‑approved prodrug irinotecan, and indicating graphene as a promising platform for delivering low‑solubility aromatic drugs.

Abstract

It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nanographene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO−PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analogue, SN38, noncovalently via π−π stacking. The resulting NGO−PEG−SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO−PEG−SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.