Injectable hydrogel nanoarchitectonics with near-infrared controlled drug delivery for in situ photothermal/endocrine synergistic endometriosis therapy

Endometriosis is a common gynecological disease in women of childbearing age. Commonly used treatment methods, such as endocrine and surgical therapies, display poor therapeutic effects with a high relapse probability. Thus, novel treatments for endometriosis are required. In our study, polydopamine (PDA), letrozole (LTZ), and agarose (AG) hydrogels were combined to construct an injectable hydrogel with near-infrared controlled drug delivery named LTZ-PDA@AG hydrogel for endometriosis treatment. The release of letrozole can be accurately controlled by the near-infrared light intensity, exposure duration, polydopamine concentration, and hydrogel composition. Meanwhile, we isolated endometrial stromal cells from endometrium in patients with endometriosis, and constructed the rats' model of endometriosis to verify the biological effects of LTZ-PDA@AG hydrogel. Owing to the sufficiently deep penetration of near-infrared light, the LTZ-PDA@AG hydrogel displayed a high temperature increase for efficient photothermal therapy. In addition, high local temperatures can further enhance the diffusion and penetration of letrozole, thereby achieving excellent therapeutic effect in vivo. Importantly, the in vivo and vitro test demonstrated the capacity of the nanocomposite hydrogel for endocrine-photothermal synergistic therapy and the biocompatibility. Our work proposes a novel concept for precision endometriosis therapy by photothermal-enhanced endocrine therapy for endometriosis, which is proposed for the first time for the treatment of endometriosis and demonstrates excellent potential for further clinical translation.