Size Dependent Liposomal Fusion and H-Bonded Sticky Aggregation Induced by Gold Nanoclusters

We present a novel approach to quantitatively control liposomal fusion and aggregation, depending upon the surface charge and functionalities, using fluorescent gold nanoclusters (AuNCs). We show that ligand-protected ultrasmall AuNCs are excellent fusogenic materials that follow renal clearance pathways after induction of liposomal fusion, especially with dipalmitoylphosphatidylcholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) mixed in a 3:1 molar ratio mimicking the brain cells. AuNCs show interesting photophysics and emit from visible to near-infrared (NIR) regions depending upon the quantum confinement effect that is directly related to the Fermi wavelength and size of the NCs. Herein, we have synthesized orange-emitting l-glutathione (GSH) coated Au₂₅(GSH)₁₈ NCs (GSH-AuNCs) to be applied on lipid membranes to observe the fusogenic property on small and giant unilamellar vesicles (SUVs and GUVs). We noticed that the GSH-AuNCs easily attach to the surface of the DPPC liposomes and facilitate complete fusion through favorable lipid mixing. The fusion rate is higher (80%) for the DPPC SUVs compared to that for the GUVs, which has been explained experimentally. On the contrary, the DMPG SUVs aggregate, with minimal lipid mixing, in the presence of the GSH-AuNCs. We noted a ∼70% fusion efficiency for SUVs with mixed DPPC:DMPG composition (3:1 molar ratio). This is the first report on fusion and aggregation of liposomes guided by ligand functionalities and surface charge of AuNCs.