Functionally integrating nanoparticles alleviate deep vein thrombosis in pregnancy and rescue intrauterine growth restriction

作者全名："Cheng, Juan; Zhang, Siqi; Li, Chenwen; Li, Ke; Jia, Xiaoyan; Wei, Quanfang; Qi, Hongbo; Zhang, Jianxiang"

作者地址："[Cheng, Juan; Zhang, Siqi; Li, Ke; Jia, Xiaoyan; Qi, Hongbo] Chongqing Med Univ, Chongqing Key Lab Maternal & Fetal Med, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Cheng, Juan; Qi, Hongbo] Chongqing Med Univ, Women & Childrens Hosp, Chongqing 401147, Peoples R China; [Cheng, Juan; Zhang, Siqi; Li, Ke; Jia, Xiaoyan] Chongqing Med Univ, Dept Obstet, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Cheng, Juan; Li, Chenwen; Zhang, Jianxiang] Third Mil Med Univ, Coll Pharm, Dept Pharmaceut, Army Med Univ, Chongqing 400038, Peoples R China; [Wei, Quanfang] Third Mil Med Univ, Coll Basic Med Sci, Biomed Anal Ctr, Army Med Univ, Chongqing 400038, Peoples R China; [Zhang, Jianxiang] Third Mil Med Univ, State Key Lab Trauma Burn & Combined Injury, Army Med Univ, Chongqing 400038, Peoples R China"

通信作者："Qi, HB (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Maternal & Fetal Med, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Qi, HB (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Chongqing 401147, Peoples R China.; Zhang, JX (通讯作者)，Third Mil Med Univ, Coll Pharm, Dept Pharmaceut, Army Med Univ, Chongqing 400038, Peoples R China.; Zhang, JX (通讯作者)，Third Mil Med Univ, State Key Lab Trauma Burn & Combined Injury, Army Med Univ, Chongqing 400038, Peoples R China."

来源：NATURE COMMUNICATIONS

ESI学科分类：　

WOS号：WOS:000887967900005

JCR分区：Q1

影响因子：16.6

年份：2022

卷号：13

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："There is still unmet demand for effective, safe, and patient-friendly anti-thrombotics to treat deep vein thrombosis (DVT) during pregnancy. Here we first engineer a bioactive amphiphile (TLH) by simultaneously conjugating Tempol and linoleic acid onto low molecular weight heparin (LMWH), which can assemble into multifunctional nanoparticles (TLH NP). In pregnant rats with DVT, TLH NP can target and dissolve thrombi, recanalize vessel occlusion, and eradicate the recurrence of thromboembolism, thereby reversing DVT-mediated intrauterine growth restriction and delayed development of fetuses. Mechanistically, therapeutic effects of TLH NP are realized by inhibiting platelet aggregation, facilitating thrombolysis, reducing local inflammation, attenuating oxidative stress, promoting endothelial repair, and increasing bioavailability. By decorating with a fibrin-binding peptide, targeting efficiency and therapeutic benefits of TLH NP are considerably improved. Importantly, LMWH nanotherapies show no toxicities to the mother and fetus at the dose 10-time higher than the examined therapeutic dosage. There is still an unmet need for effective and safe drugs to treat deep vein thrombosis during pregnancy, a life-threatening condition for the mother and fetus. Here, the authors show that engineered multifunctional nanoparticles can site-specifically dissolve thrombi and reverse deep vein thrombosis-mediated intrauterine growth restriction and delayed development of fetuses in pregnant rats."

基金机构："National Natural Science Foundation of China [82171662, U21A20346]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0856]; Program for Scientific and Technological Innovation Leader of Chongqing [CQYC20210302362]; Program for Distinguished Young Scholars of TMMU"

基金资助正文："This study was supported by the National Natural Science Foundation of China (No. 82171662, to H.Q.), Joint Funds of the National Natural Science Foundation of China (No. U21A20346, to H.Q.), the Natural Science Foundation of Chongqing (No. CSTB2022NSCQ-MSX0856, to J.C.), the Program for Scientific and Technological Innovation Leader of Chongqing (No. CQYC20210302362, to J.Z.), and the Program for Distinguished Young Scholars of TMMU (to J.Z.)."