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

Drug treatment is required for both resectable and unresectable cancers to strive for any meaningful patient outcomes improvement. 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, we introduce a microfabrication concept, termed Hierarchical Multiple Polymers Immobilization (HMPI), and engineer biodegradable polymers-based hierarchical microdevices (HMDs) that can pre-program any desired controlled release profiles. 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 was implemented, respectively. Preclinical models of postsurgical pancreatic, postsurgical breast, and unresectable breast cancer were established, and the designed hierarchical microdevices demonstrated well-tolerable and effective treatments for inhibiting tumor growth, recurrence, and metastasis. The proposed HMPI strategy allows us to create 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. This article is protected by copyright. All rights reserved.