Artificial nano-red blood cells nanoplatform with lysosomal escape capability for ultrasound imaging-guided on-demand pain management

Postoperative pain management would benefit significantly from an anesthetic that could take effect in an on-demand manner. An ultrasound would be an appropriate tool for such nanoplatform because it is widely used in clinical settings for ultrasound-guided anesthesia. Herein, we report a nanoplatform for postoperative on-demand pain management that can effectively enhance their analgesic time while providing ultrasonic imaging. Levobupivacaine and perfluoropentane were put into dendritic mesoporous silica and covered with red blood cell membranes to make the pain relief last longer in living organisms. The generated nanoplatform with gas-producing capability is ultrasonic responsive and can finely escape from the lysosomal in cells under ultrasound irradiation, maximizing the anesthetic effect with minimal toxicity. Using an incision pain model in vivo, levobupivacaine's sustained and controlled release gives pain reduction for approximately 3 days straight. The duration of pain relief is over 20 times greater than with a single injection of free levobupivacaine. Effective pain management was reached in vivo, and the pain reduction was enhanced by repeated ultrasonic irradiation. There was no detectable systemic or tissue injury under either of the treatments. Thus, our results suggest that nanoplatform with lysosomal escape capability can provide a practical ultrasound imaging-guided on-demand pain management strategy. STATEMENT OF SIGNIFICANCE: On-demand pain management is essential to postoperative patients. However, the traditional on-demand pain management strategy is hampered by the limited tissue penetration depth of near-infrared stimuli and the lack of proper imaging guidance. The proposed research is significant because it provides a nanoplatform for deep penetrated ultrasound controlled pain management under clinical applicable ultrasound imaging guidance. Moreover, the nanoplatform with prolonged retention time and lysosomal escape capability can provide long-term pain alleviation. Therefore, our results suggest that nanoplatform with lysosomal escape capability can provide an effective strategy for ultrasound imaging-guided on-demand pain management.