摘要Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of tran-sient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degra-dation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanopar-ticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targeta-bility without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclu-sion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.