Biodegradable Imprinted Polymer Based on ZIF-8/DOX-HA for Synergistically Targeting Prostate Cancer Cells and Controlled Drug Release with Multiple Responses

Improving the drug loading and delivery efficiency of biodegradable nanomaterials used for targeting prostate cancer (PCa) remains a challenging task. To accomplish this task, herein, a new surface molecularly imprinted polymer (ZIF-8/DOX-HA@MIP) was designed and constructed with a hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework loaded with doxorubicin (DOX) as a substrate and a responsive molecularly imprinted polymer film as a shell. Owing to the large surface area of ZIF-8, DOX was successfully loaded into the ZIF-8/DOX-HA@MIP with a high drug loading efficiency (more than 88%). In vitro cell experiments have shown that the strengthened targeting ability of ZIF-8/DOX-HA@MIP to PCa cells was realized through the synergistic effect of HA and the molecularly imprinted membrane. Under the condition of simulated tumor microenvironment solution, Zn species were released and the particle size of ZIF-8/DOX-HA@MIP decreased gradually by the synergistic effect of hyaluronidase, pH, and glutathione, showing excellent biodegradability. In vivo antitumor research indicated the excellent antitumor activity and biocompatibility of ZIF-8/DOX-HA@MIP. The multifunctional ZIF-8/DOX-HA@MIP constructed herein provides a novel impetus for the development of targeted drug delivery in PCa treatment and a new strategy for treating other tumors.