CD44 Receptor-driven graphene oxide based nanocarriers for a selective cancer therapy

Interactions between hyaluronic acid (HA) and the CD44 receptor represent a key mechanism in tumor cell
recognition and selective drug uptake. In this study, we compare the efficacy of a graphene oxide (GO)-based
nanoplatform in two cell lines with markedly different CD44 expression levels. The aim is to investigate how HA
functionalization and its concentration influence the biological behavior of these GO nanocarriers designed for
targeted delivery of doxorubicin (DOX). The nanoplatform was prepared by sequential PEGylation of nanosized
GO, followed by HA conjugation at three concentrations (0.1, 1, and 10 mg/mL) and subsequent DOX loading.
Spectroscopic and microscopic analyses confirmed stepwise surface modification, formation of a stable polymer
coating, and successful DOX incorporation through π–π stacking and hydrogen bonding. Biological assays
demonstrated that HA enhances CD44-mediated internalization and increases anticancer activity in CD44⁺ HT-
1080 cells, while the GO@PEG carrier alone showed minimal cytotoxicity, highlighting its good biocompati-
bility. In contrast, CD44⁻ SKBR3 cells displayed limited uptake and higher viability, consistent with weaker
HA–CD44 interactions and lower receptor expression. Confocal microscopy and Raman spectroscopy visualized
effective intracellular accumulation and perinuclear localization of the nanocarrier, further confirming selective
internalization mechanisms. Overall, the results provide important insight into the role of HA in improving the
specificity, cellular uptake, and safety of GO-based nanoplatforms. The study underscores the significance of
CD44 receptor levels in determining therapeutic efficiency and supports the development of receptor-targeted,
biocompatible nanocarrier systems for precision cancer therapy.