Nano-Sized Liposomesfor Click-Chemistry-Based SelectiveGuiding of Immune Cells to Neuroblastoma

Neuroblastoma is a prevalent extracranial solid tumor that mainly affects children, for which current therapies often cause significant side effects due to limited specificity. To address this, nanomedicine has introduced engineered nanocarriers for targeted drug delivery, yet challenges such as poor tumor perfusion and immune clearance remain. Herein, we present an approach using bifunctional nanosized liposomes to enhance immune cell targeting of neuroblastoma cells through click chemistry. These liposomes, functionalized with azide or strained alkyne groups and targeting moieties, were designed to selectively label macrophages and neuroblastoma cells, facilitating their recognition through bio-orthogonal chemical reactions. In vitro studies under physiological flow conditions demonstrated the successful labeling of both cell types and subsequent interaction, mimicking the in vivo environment. This strategy could change the current paradigm of cell-based treatments for solid tumors like neuroblastoma, owing to an improvement in the immune cell targeting efficacy.