Self-assembled ultrasmall silver nanoclusters on liposome for topical antimicrobial delivery

Silver nanomaterials represent one of the most efficient and promising strategies for bacterial disinfection considering the growing resistance threats of conventional antibiotics. Ultrasmall silver nanocluster (Ag NC) is the most exciting next generation silver based nanomaterial with intriguing physiochemical properties of sub-2 nm core size and abundant active Ag⁺ ions, while the study of Ag NC based antibiotics is still in its infancy. The current applications of Ag NCs under physiological condition are susceptibly hindered by spontaneous aggregation and silver oxidation, resulting in the loss of antimicrobial efficiency. In this work, a core-shell structured Ag NC based nanocomposite was synthesized through the encapsulation of Ag NCs in the phosphatidylcholine liposomes (Ag NC@liposome). This liposomal Ag NC was demonstrated as a broad-spectrum antimicrobial agent with killing efficiency >99.99 % and wide pH range tolerance of pH = 5‒9. An in-depth investigation shows that the core-shell construct of this nanocomposite is essential for controlled release of Ag⁺ ions and sustainable reactive oxygen species (ROS) production. More importantly, this nanocomposite possesses minimum cytotoxicity on mammalian cells and can be successfully applied for wound disinfection in vivo. To our knowledge, this is the first example of Ag NC based liposomal formulation. This sophisticated design would be indicative to the research and development of Ag NCs in portable bandages and implantable devices for topical antimicrobial delivery.