Endogenous Zinc Ion-Triggered In-Situ Gelation Enables Zn Capture to Reprogramme Benign Hyperplastic Prostate Microenvironment and Shrink Prostate

Benign prostatic hyperplasia (BPH) as the leading cause of urination disorder is still a refractory disease, and there have no satisfied drugs or treatment protocols yet. With identifying excessive Zn2+, inflammation, and oxidative stress as the etiology of aberrant hyperplasia, an injectable sodium alginate (SA) & glycyrrhizic acid (GA)-interconnected hydrogels (SAGA) featuring Zn2+-triggered in-situ gelation have been developed to load lonidamine for reprogramming prostate microenvironment and treating BPH. Herein, SAGA hydrogels can crosslink with Zn2+ in BPH via coordination chelation and switch free Zn2+ to bound ones, consequently alleviating Zn2+-arised inflammation and glycolysis. Beyond capturing Zn2+, GA with intrinsic immunoregulatory property can also alleviate local inflammation and scavenge ROS. Intriguingly, Zn2+ chelation-bridged interconnection in SAGA enhances its mechanical property and regulates the degradation rate to enable continuous lonidamine release, favoring hyperplastic acini apoptosis and further inhibiting glycolysis. These multiple actions cooperatively reprogramme BPH microenvironment to alleviate characteristic symptoms of BPH and shrink prostate. RNA sequencing reveals that chemotaxis, glycolysis and TNF inflammation-related pathways associated with M1-like phenotype polarization are discerned as the action rationales of such endogenous Zn2+-triggered in-situ hydrogels, providing a candidate avenue to treat BPH. This article is protected by copyright. All rights reserved.