Seminiferous Tubules‐Targeted Resveratrol Carbon Dots With Sertoli Cell Biomimetic Vesicles Fusion for Improving Spermatogenesis of Cryptorchidism

Impaired blood-testis barrier (BTB) integrity, induced by oxidative stress, is one of the primary factors leading to spermatogenic disorders in cryptorchidism. Therefore, the targeted elimination of testicular oxidative stress and repair of the BTB are promising strategies for promoting spermatogenesis in patients with cryptorchidism. This study aimed to demonstrate the potential of Sertoli cell membrane-camouflaged biomimetic vesicles loaded with resveratrol carbon dots (RCD@PCy@EVs) as a therapeutic nanoagent for cryptorchidism treatment in vivo. The prepared RCD@PCy@EVs are actively targeted to the seminiferous tubules by leveraging the homing tendency of the Sertoli cell membrane, guided by fluorescence imaging. The RCD@PCy@EVs not only reshape the redox microenvironment of the seminiferous tubules and alleviate inflammatory responses by scavenging reactive oxygen species, but they also increase the expression of the tight junction protein β-catenin and restore BTB integrity, which is associated with the activation of the SIRT1/AMPKα/FOXO1 signaling pathway. More importantly, functional spermatogenesis is markedly improved by RCD@PCy@EVs, effectively restoring reproductive function in cryptorchid mice. The RCD@PCy@EVs-mediated therapy for cryptorchidism offers a novel strategy for treating male infertility.