基于DSPE-PEG-DOTA的壓電納米平臺在腦膠質瘤中的應用探索

鏈接：https://d.wanfangdata.com.cn/periodical/sdykdxxb202306002

作者： 陳治光  張巍  何文

摘要：

目的：探討基于偏氟乙烯(vinylidene fluoride,VDF)和三氟乙烯(trifluoroethylene,TrFE)的共聚物[poly(VDF-TrFE),P(VDF-TrFE)]構建的復合壓電納米粒子在腦膠質瘤細胞中*和成像的效能.方法 對P(VDF-TrFE)壓電材料進行晶型重塑和親水性改善,通過點擊化學反應將精氨酰-甘氨酰-天冬氨酸合成肽(Arg-Gly-Asp,RGD)連接到二硬脂酰基磷脂酰乙醇胺-聚乙二醇-馬來酰亞胺脂[1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-maleimide,DSPE-PEG-Mal]上;同時以DSPE-PEG-四氮雜環配體(DSPE-PEG-tetranitroheterocyclic ligand,DSPE-PEG-DOTA)為底液,加入一定量醋酸釓溶液,通過螯合獲得 DSPE-PEG-DOTA-釓造影劑(DSPE-PEG-DOTA-Gd);按比例將重塑后的 P(VDF-TrFE)、DAPE-PEG-Mal-RGD 和DSPE-PEG-DOTA-Gd混合,最后獲得復合壓電納米粒子P(VDF-TrFE)@DOTA-Gd@RGD,對其進行表征以及用于細胞層面實驗研究.結果 P(VDF-TrFE)@DOTA-Gd@RGD復合壓電納米粒子具有*的穩定性,尤其是在達爾伯克氏必需基本培養基(Dulbecco's modified eagle medium,DMEM)中,其粒徑隨時間變化保持在 160 nm左右;經過晶型重塑后,P(VDF-TrFE)@DOTA-Gd@RGD的壓電性能明顯提高,表面電勢約為 4.2 mV;該納米粒子可作為磁共振成像(magnetic resonance imaging,MRI)顯像劑,而且在超聲激發下,P(VDF-TrFE)@DOTA-Gd@RGD復合壓電納米粒子能產生大量活性氧,抑制了膠質瘤細胞的增殖、侵襲和遷移能力,同時還促進其凋亡.結論 P(VDF-TrFE)@DOTA-Gd@RGD復合壓電納米粒子作為MRI顯像劑可以用于腦膠質瘤的定位,且可以作為一種聲敏劑用于腦膠質瘤細胞的聲動力*.

譯文：

Objective To explore the efficacy of composite piezoelectric nanoparticles constructed based on poly(vinylidene fluoride)-trifluoroethylene[P(VDF-TrFE)]in the treatment and imaging of glioma.Methods P(VDF-TrFE)piezoelectric materials were reshaped in crystal form and improved in hydrophilicity,and Arg-Gly-Asp(RGD)targeted peptides were connected to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-maleimide(DSPE-PEG-Mal)by click chemistry reaction.In addition,DSPE-PEG-tetranitroheterocyclic ligand(DSPE-PEG-DOTA)was mixed with a certain amount of gadolinium acetate solution was added to obtain DSPE-PEG-DOTA-Gd through chelation.And then the P(VDF-TrFE),DAPE-PEG-Mal RGD,and DSPE-PEG-DOTA-Gd in proportion were mixed to obtain composite piezoelectric nanoparticles P(VDF-TrFE)@DOTA-Gd@RGD.The obtained nanoparticles were characterized and assesed.Results P(VDF-TrFE)@DOTA-Gd@RGD composite piezoelectric nanoparticles have excellent stability,especially in Dulbecco's modified eagle medium(DMEM)solutions where their particle size remained around 160 nm over time.After crystal reshaping,the piezoelectric performance of P(VDF-TrFE)@DOTA-Gd@RGD is significantly improved,with a surface potential of approximately 4.2 mV.The nanoparticles could be used as a magnetic resonance imaging(MRI)agent.Under ultrasound excitation,P(VDF-TrFE)@DOTA-Gd@RGD composite piezoelectric nanoparticles generated a large amount of reactive oxygen species,inhibited the proliferation,invasion,and migration ability of glioma cells,and promoted their apoptosis.Conclusion P(VDF-TrFE)@DOTA-Gd@RGD composite piezoelectric nanoparticles could be used as an MRI agent for the localization of brain gliomas and as a sound sensitive agent for sonodynamic therapy of glioma.

DOI： 10.3969/j.issn.1006-7795.2023.06.002

西安齊岳生物提供相關產品：

mPEG-Palmitic acid

mPEG-STA

DSPE-mPEG

DSPE-Biotin

16:0 Biotinyl Cap PE

16:0 Folate Cap PE

DSPE-Thiol，DSPE-SH

DSPE-COOH，DSPE-Succinic acid

DSPE-MAL，DSPE-Maleimide

DSPE-NHS

DSPE-Hyaluronate

DSPE-Dextran

DSPE-Chitosan

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