Molecularly Imprinted Polymer-Based Smart Prodrug Delivery System for Specific Targeting, Prolonged Retention, and Tumor Microenvironment-Triggered Release.

Prodrug and drug delivery systems are two effective strategies for improving the selectivity of chemotherapeutics. Molecularly imprinted polymers (MIPs) have emerged as promising carriers in targeted drug delivery for cancer treatment, but they have not yet been integrated with the prodrug strategy. Reported here is an MIP-based smart prodrug delivery system for specific targeting, prolonged retention time, and tumor microenvironment-triggered release. 5'-Deoxy-5-fluorocytidine (DFCR) and sialic acid (SA) were used as a prodrug and a marker for tumor targeting, respectively. Their co-imprinted nanoparticles were prepared as a smart carrier. Prodrug-loaded MIP specifically and sustainably accumulated at the tumor site and then gradually released. Unlike conventional prodrug designs, which often require in-liver bioconversion, this MIP-based prodrug delivery is liver-independent but tumor-dependent. Thus, this study opens new access to the development of smart prodrug delivery nanoplatforms.