Abstract
Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeu-tic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic sys-tem to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encap-sulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoa-gent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.
基金项目
国家自然科学基金(82001189)
Project Tackling of Key Scientific and Technical Problems of Henan Provine(232102311163)
维普
万方数据