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

Juan Cheng, Siqi Zhang, Chenwen Li, Ke Li, Xiaoyan Jia, Quanfang Wei, Hongbo Qi () and Jianxiang Zhang ()
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Juan Cheng: The First Affiliated Hospital of Chongqing Medical University
Siqi Zhang: The First Affiliated Hospital of Chongqing Medical University
Chenwen Li: Third Military Medical University (Army Medical University)
Ke Li: The First Affiliated Hospital of Chongqing Medical University
Xiaoyan Jia: The First Affiliated Hospital of Chongqing Medical University
Quanfang Wei: Third Military Medical University (Army Medical University)
Hongbo Qi: The First Affiliated Hospital of Chongqing Medical University
Jianxiang Zhang: Third Military Medical University (Army Medical University)

Nature Communications, 2022, vol. 13, issue 1, 1-21

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-34878-2

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