Engineered Hierarchical Microdevices Enable Pre-Programmed Controlled Release for Postsurgical and Unresectable Cancer Treatment.

Abstract

Drug treatment is required for both resectable and unresectable cancers to strive for any meaningful improvement inpatient outcomes. However, the clinical benefit of receiving conventional systemic administrations is often less than satisfactory. Drug delivery systems are preferable substitutes but still fail to meet diverse clinical demands due to the difficulty in programming drug release profiles. Herein, a microfabrication concept, termed "Hierarchical Multiple Polymers Immobilization" (HMPI), is introduced and biodegradable-polymer-based hierarchical microdevices (HMDs) that can pre-program any desired controlled release profiles are engineered. Based on the first-line medication of pancreatic and breast cancer, controlled release of single gemcitabine and the doxorubicin/paclitaxel combination in situ for multiple courses is implemented, respectively. Preclinical models of postsurgical pancreatic, postsurgical breast, and unresectable breast cancer are established, and the designed HMDs are demonstrated as well-tolerable and effective treatments for inhibiting tumor growth, recurrence, and metastasis. The proposed HMPI strategy allows the creation of tailorable and high-resolution hierarchical microstructures for pre-programming controlled release according to clinical medication schedules, which may provide promising alternative treatments for postsurgical and unresectable tumor control.