The proposed approach encompasses three primary aims. In Aim 1, I will synthesize, characterize, and optimize dePFCnDs that can be used for US/PA imaging and FUS activation. Aim 2 focuses on the design and development of the integrated US/PA imaging and FUS activation system to monitor and activate drug-loaded dePFCnDs. Additionally, dePFCnD dynamic behavior will be studied to optimize FUS parameters for safe and efficient drug delivery. Aim 3 seeks to demonstrate the integrated system’s efficacy for precise drug delivery and monitoring in immunotherapy by encapsulating adjuvants into the dePFCnDs and releasing them to the antigen-presenting cells in primary tumors or tumor-draining lymph nodes. This study can advance drug delivery systems by introducing a method for the non-invasive, precise, and efficient delivery of hydrophilic drugs. Developing dePFCnDs and a pre-clinical/clinical US/PA image-guided FUS system could overcome current limitations in drug encapsulation and unintended release, reducing side effects associated with systemic drug delivery by enabling more precise and effective targeted drug delivery.