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 cellrecognition and selective drug uptake. In this study, we compare the efficacy of a graphene oxide (GO)-basednanoplatform in two cell lines with markedly different CD44 expression levels. The aim is to investigate how HAfunctionalization and its concentration influence the biological behavior of these GO nanocarriers designed fortargeted delivery of doxorubicin (DOX). The nanoplatform was prepared by sequential PEGylation of nanosizedGO, 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 polymercoating, and successful DOX incorporation through π–π stacking and hydrogen bonding. Biological assaysdemonstrated 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 weakerHA–CD44 interactions and lower receptor expression. Confocal microscopy and Raman spectroscopy visualizedeffective intracellular accumulation and perinuclear localization of the nanocarrier, further confirming selectiveinternalization mechanisms. Overall, the results provide important insight into the role of HA in improving thespecificity, cellular uptake, and safety of GO-based nanoplatforms. The study underscores the significance ofCD44 receptor levels in determining therapeutic efficiency and supports the development of receptor-targeted,biocompatible nanocarrier systems for precision cancer therapy.