Synergistic clearance of intracellular pathogens by hyaluronan-streptomycin micelles encapsulated with rapamycin.

Many pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize inside, which protects them from the attack by host immune system and antibiotics. A novel amphiphilic molecule was synthesized through conjugation of streptomycin and decylamine to hyaluronan. Rapamycin was encapsulted by the spontaneous self-assembly of hyaluronan-based amphiphilic molecules. The newly formed micelles not only facilitated the entry of drugs into host cells in part via CD44 phagocytic receptor, released streptomycin in the acidic compartment, but also could activate autophagy. The micelles elicited an efficient killing capacity against intracellular bacteria through the promotion of streptomycin uptake and rapamycin-initiated activation of autophagy. This strategy might highlight an acid-sensitive hyaluronan-based drug delivery system for effective treatment of intracellular infections.