Biocompatible Assessment of Erythrocyte Membrane-Camouflaged Polymeric PLGA Nanoparticles in Pregnant Mice: Both on Maternal and Fetal/Juvenile Mice

Abstract

Sailing Chen,1,* Dongyan Tian,1,* Xuewei Yang,1,* Qingqing Yin,1 Li Li,1 Yijing Lin,1 Shuangshuang Liu,1 Huiqian Chen,1 Mingyao Zhang,1 Jiajin Lin,2 Xiaosheng Lu,1 Ping Duan,1 Yijie Chen1,3,4 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Blood Transfusion, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Duan; Yijie Chen, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, 109 West Xueyuan Road, Wenzhou, 325027, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]; [email protected]: Poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with the membrane of red blood cells (RBC-NP) have been applied in various biomedical fields. Despite the well-documented great biocompatibility, the potential toxicity of RBC-NP on maternal mice or their developing fetuses during pregnancy, or juvenile mice post-birth, remains unclear, which warrants a systematic evaluation.Methods: We fabricate an RBC-NP with approximately 50 nm in diameter (RBC-NP-50). Upon RBC-NP-50, pregnant mice are intravenously injected with this nanoparticle either at a single high dose of 400 mg/kg (1HD) or a low dose of 200 mg/kg for 3 times (3LD). Afterwards, the biocompatible assessments are performed at 48 h after the final injection or 21 d post-birth/partum both on maternal and fetal/juvenile mice.Results: RBC-NP-50 is capable of accumulating in the placenta and then passing through the blood-fetal barrier (BFB) into the fetus. On 48 h after RBC-NP-50 exposure, no significant dose-dependent toxicity is observed in maternal mice including blood biochemistry, inflammatory factors, progesterone level, histological analysis, etc, whereas fetal brains reveal remarkable differentially expressed genes analyzed by transcriptome sequencing. On 21 d post-birth, those genes’ expression in juvenile mice is alleviated, along with negligible differences in behavioral evaluations including surface righting test, negative geotaxis test, cliff avoidance test, and olfactory orientation test.Conclusion: These results indicate that RBC-NP is considered to be generally safe and biocompatible both for maternal mice and fetus during pregnancy, and for the subsequent juvenile mice post-birth, although future studies will need to examine higher dosage or longer-term measurements.Keywords: erythrocyte membrane, pregnancy, fetus, biocompatibility, RNA sequencing

Keywords

• erythrocyte membrane
• pregnancy
• fetus
• biocompatibility
• rna sequencing