The targetable nanoparticle BAF312@cRGD-CaP-NP represses tumor growth and angiogenesis by downregulating the S1PR1/P-STAT3/VEGFA axis in triple-negative breast cancer.
机构：[1]State Key Laboratory of Oncogenes and Related Genes, Shanghai CancerInstitute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University,Shanghai 200032, China[2]Department of Bone and Joint Surgery, Departmentof Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiao TongUniversity, Shanghai 200011, China[3]Sichuan Academy of Chinese MedicineScience, Chengdu 610041, Sichuan, China[4]Department of Ultrasound, ShanghaiGeneral Hospital, Shanghai Jiao Tong University School of Medicine, 100Haining Road, Shanghai 200080, China
Overexpressed vascular endothelial growth factor A (VEGFA) and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) cause unrestricted tumor growth and angiogenesis of breast cancer (BRCA), especially triple-negative breast cancer (TNBC). Hence, novel treatment strategy is urgently needed.We found sphingosine 1 phosphate receptor 1 (S1PR1) can regulate P-STAT3/VEGFA. Database showed S1PR1 is highly expressed in BRCA and causes the poor prognosis of patients. Interrupting the expression of S1PR1 could inhibit the growth of human breast cancer cells (MCF-7 and MDA-MB-231) and suppress the angiogenesis of human umbilical vein endothelial cells (HUVECs) via affecting S1PR1/P-STAT3/VEGFA axis. Siponimod (BAF312) is a selective antagonist of S1PR1, which inhibits tumor growth and angiogenesis in vitro by downregulating the S1PR1/P-STAT3/VEGFA axis. We prepared pH-sensitive and tumor-targeted shell-core structure nanoparticles, in which hydrophilic PEG2000 modified with the cyclic Arg-Gly-Asp (cRGD) formed the shell, hydrophobic DSPE formed the core, and CaP (calcium and phosphate ions) was adsorbed onto the shell; the nanoparticles were used to deliver BAF312 (BAF312@cRGD-CaP-NPs). The size and potential of the nanoparticles were 109.9 ± 1.002 nm and - 10.6 ± 0.056 mV. The incorporation efficacy for BAF312 was 81.4%. Results confirmed BAF312@cRGD-CaP-NP could dramatically inhibit tumor growth and angiogenesis in vitro and in MDA-MB-231 tumor-bearing mice via downregulating the S1PR1/P-STAT3/VEGFA axis.Our data suggest a potent role for BAF312@cRGD-CaP-NPs in treating BRCA, especially TNBC by downregulating the S1PR1/P-STAT3/VEGFA axis.
基金：
This work was supported by the National Natural Science Foundation of
China (Grant Number 81972886 and Grant Number 81773272); National
Science and Technology Major New Drug Innovation Project (Grant Number
2018ZX09731013).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|2 区工程技术
小类|2 区生物工程与应用微生物3 区纳米科技
最新[2023]版：
大类|1 区生物学
小类|1 区生物工程与应用微生物2 区纳米科技
第一作者：
第一作者机构：[1]State Key Laboratory of Oncogenes and Related Genes, Shanghai CancerInstitute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University,Shanghai 200032, China
共同第一作者：
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推荐引用方式(GB/T 7714)：
Gong Ke,Jiao Juyang,Xu Chaoqun,et al.The targetable nanoparticle BAF312@cRGD-CaP-NP represses tumor growth and angiogenesis by downregulating the S1PR1/P-STAT3/VEGFA axis in triple-negative breast cancer.[J].Journal of nanobiotechnology.2021,19(1):165.doi:10.1186/s12951-021-00904-6.
APA：
Gong Ke,Jiao Juyang,Xu Chaoqun,Dong Yang,Li Dongxiao...&Duan Yourong.(2021).The targetable nanoparticle BAF312@cRGD-CaP-NP represses tumor growth and angiogenesis by downregulating the S1PR1/P-STAT3/VEGFA axis in triple-negative breast cancer..Journal of nanobiotechnology,19,(1)
MLA：
Gong Ke,et al."The targetable nanoparticle BAF312@cRGD-CaP-NP represses tumor growth and angiogenesis by downregulating the S1PR1/P-STAT3/VEGFA axis in triple-negative breast cancer.".Journal of nanobiotechnology 19..1(2021):165
生物学