Phospholipid‐Drug Conjugates Self‐Organized into Well‐Defined Supramolecular Nanotubes for Efficient Drug Delivery

Abstract Controlled self‐organization of amphiphilic phospholipid camptothecin (CPT) conjugates (named PCCs) selectively forms supramolecular nanotubes with varying lengths and polydispersity. Our study elucidates the underlying mechanisms governing PCC assembly, demonstrating that π–π stacking interactions derived from the planar, conjugated structure of CPT play a pivotal role in nanotube formation. Precise modulation of the hydrophobic characteristics of PCC linkers enables fine‐tuning of π‐stacking strength, thereby controlling the length of the nanotubes, ranging from the nano‐ to micro‐scale. With exceptionally high drug‐loading efficiencies (43.9% to 52.3%) and stimulus‐responsive release properties, the optimized PCC nanotubes exhibit tumor‐selective cytotoxicity of 20‐ to 50‐fold greater potency against tumor cells compared to normal cells. Furthermore, PCC nanotubes of intermediate length (0.3–0.5 µm) display prolonged circulation times than conventional liposomes, resulting in enhanced tumor‐targeting and therapeutic efficacy.