In this Prostate Cancer Research Program Postdoctoral Training Award, the research goal is to develop a prostate cancer-targeted nanoplatform for imaging and drug delivery using a hyaluronic acid HA-based nanoparticle. The HA-degrading enzyme, hyaluronidase Hyal, is used as a biomarker for progressive prostate cancer cells. By using nanomedicine, anticancer drugs can localize at the specific tumor site thereby reducing side effects on healthy tissue, which is particularly important when the average age of the patient at the time of diagnosis is 67. The HA-based nanoparticle carries anti-cancer drugs in it center cores, and the drug can be released by enzymatic degradation via HYAL1. Importantly, the system can target CD44 positive prostate cancer stem cells through intrinsic HA-CD44 receptor interactions and deliver drugs directly to tumor-initiating cells. The study aims to meet the PCRP Overarching Challenge to develop effective treatments for men with high risk of metastatic prostate cancer. The training goal is to apply the PIs interdisciplinary training in imaging and nanotechnology towards clinical translation of theranostic therapeutic plus diagnostic agents.