Self-assembling hyaluronic acid–lipid conjugates as platforms for targeted drug delivery

Ilaria Andreana – Posdoc, University of Torino; Stefano Boetti – Researcher Fellow, University of Torino; Maria Emilia Cano – Researcher, Université de Picardie Jules Verne; Chiara Riganti – Full Professor, University of Torino; Barbara Stella – Professor, University of Torino; Silvia Arpicco – Full Professor, University of Torino; José Kovensky – Professor, Université de Picardie Jules Verne

Introduction:

Hyaluronic acid (HA) is a glycosaminoglycan involved in tumor progression and inflammation that specifically binds the CD44 receptor, overexpressed in several cancers [1]. Previous HA oligosaccharide–PEG–phospholipid conjugates showed enhanced uptake in CD44-positive lung cancer cells but failed to self-assemble, likely due to PEG hydrophilicity [2]. To overcome this limitation, an azido-functionalized HA octasaccharide (DP8) was directly coupled to dipalmitoylphosphatidylethanolamine, generating HA-DP8-PE. This design promotes self-assembly while preserving CD44 targeting, enabling the development of HA-functionalized nanocarriers.