The Polymer Society of Korea

Abstract

Adoptive immunotherapy using natural killer (NK) cells remains limited in solid tumors due to insufficient expression of tumor-targeting ligands. To overcome this, a modular polymer “Hyaluronic acid (HA)-PEG-Lipid” was developed for cell surface engineering. The polymer structure was optimized to anchor on NK membranes, producing CD44-targeting HA-presenting NK (HANK) cells with enhanced immune synapse formation and cytotoxicity against CD44-positive pancreatic cancer cells. In mouse models, HANK cells improved tumor infiltration and suppressed tumor growth and metastasis. Glucose and boronic acid were conjugated to the polymer to enable dual targeting of GLUT1 and sialic acid, and the resulting system was successfully applied for glioblastoma and colorectal cancer treatments. This study presents a tunable surface engineering platform for immune cell functionalization and a strategy to enhance NK cell–mediated immunotherapy across diverse solid tumors.