A nanoagent for concurrent therapy of breast cancer bone metastasis and cancer-induced bone pain through SLC7A11 interruption and photodynamic therapy  

作　　者：Qi Fu Zhongming Lian Mengya Niu Yaru Huang Yanqiu Ai Long He Dandan Zhang Cuixia Zheng Jian-Jun Yang Lei Wang Dandan Tian 

机构地区：[1]Department of Anesthesiology,Pain and Perioperative Medicine,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450001,China [2]School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China [3]Translational Medical Center of Huaihe Hospital,Henan University,Kaifeng 475004,China [4]Key Laboratory of Advanced Drug Preparation Technologies,Ministry of Education,School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China

出　　处：《Chinese Chemical Letters》2024年第2期295-299,共5页中国化学快报（英文版）

基　　金：financially supported by the National Natural Science Foundation of China(No.82001189);The Project Tackling of Key Scientific and Technical Problems of Henan Provine(No.232102311163).

摘　　要：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 therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated 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 nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.

关 键 词：Breast cancer bone metastasis Cancer-induced bone pain Cystine/glutamate antiporter SORAFENIB Photodynamic therapy 

分 类 号：TB383.1[一般工业技术—材料科学与工程] TQ460.1[化学工程—制药化工] R943[医药卫生—药剂学]