Bioresorbable Depot for Sustained Release of Immunostimulatory Resiquimod in Suppressing Both Primary Triple-Negative Breast Tumors and Metastatic Occurrence.

Abstract

In light of immune facilities trafficking toward the pathological sites along upward gradient of immunostimulatory cytokines, a localized resiquimod (Toll-like receptor 7/8 agonist) release depot was manufactured for pursuit of precision immunostimulation toward intractable triple-negative breast carcinoma. In principle, resiquimod/poly(lactic-co-glycolic acid) microspheres were fabricated and embedded into injectable and biodegradable poly(ethylene glycol) (PEG)-based hydrogel. The subsequent investigations approved persistent retention of immunostimulatory resiquimod in tumors upon peritumoral administration, which consequently led to localized and consistent secretion of immunostimulatory cytokines. Initially, not only innate tumor phagocytosis but also adaptive antitumor immunities were successfully cultivated for in situ suppression of the growth of primary solid tumors, more importantly, capable of inhibiting distant pulmonary metastasis, as evidenced by observation of enormous lymphocytes selectively gathering in the pulmonary artery. Hence, our presented study provided an important clinical indication of using immunostimulatory drugs to activate potent innate and adaptive antitumor immunities for precision antitumor therapy. Further immunomodulatory strategies, such as checkpoint blockage and tumor immunogenicity, could also be complementary for development of advanced antitumor immunotherapeutics in treatment of a number of intractable tumors.