Interactions of stealth conjugated polymer nanoparticles with human whole blood.

Interactions of stealth conjugated polymer nanoparticles with human whole blood.
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DOI:
10.1039/c4tb01822b
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发表时间:
2015-03
期刊:
Journal of materials chemistry. B
影响因子:
--
通讯作者:
R. A. Khanbeigi;Z. Hashim;T. Abelha;S. Pitchford;Helen Collins;Mark A Green;L. Dailey
R. A. Khanbeigi;Z. Hashim;T. Abelha;S. Pitchford;Helen Collins;Mark A Green;L. Dailey
中科院分区:
其他
文献类型:
--
作者:
R. A. Khanbeigi;Z. Hashim;T. Abelha;S. Pitchford;Helen Collins;Mark A Green;L. Dailey

文献摘要

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光致发光共轭聚合物纳米颗粒(CPN)由于其亮度高、光稳定性高、发射光谱可调以及易于表面修饰等优点而显示出作为荧光探针的良好性能。这些新的诊断试剂的潜在细胞和临床应用是容易预见的,为研究CPN的生物相容性提供了理论基础。在这里,制造了聚苯乙炔(PPV)和聚苯乙炔(PPE)的隐形配方,并评估了它们与人体血液成分的相互作用。CPN在等渗液中是胶体稳定的,但在低至10%的补充量时,全血和血浆中的光致发光猝灭。在>150μg m L-1浓度下,隐形CPN可引起∼10%的红细胞溶血,这可能是由于配方中存在的游离聚乙二醇化表面活性物质所致。CPN与全血和分离的血小板孵育,未见血小板活化、血小板-单核细胞聚集性增加或诱导血小板聚集。有趣的是,PPE-CPN制剂以剂量依赖的方式抑制二磷酸腺苷(ADP)诱导的血小板聚集,而PPV-CPN不显示这种作用。总之,具有中性电荷、聚乙二醇化表面的隐形CPN制剂不会刺激血小板激活或聚集,但可能会在自由表面活性物质存在的情况下诱导较低程度的溶血,并可以抑制血小板聚集的生理介质,如ADP。
Photoluminescent conjugated polymeric nanoparticles (CPNs) exhibit favourable properties as fluorescent probes due to their brightness, high photostability, tunable emission spectra and ease of surface modification. Potential cellular and clinical applications of these new diagnostic agents are easily envisioned, providing a rationale to study CPN biocompatibility. Here, stealth formulations of poly phenylene vinylene (PPV) and poly phenylene ethinylene (PPE) were manufactured and their interactions with human blood components assessed. CPNs were colloidally stable in isotonic fluids, but showed photoluminescence quenching in whole blood and plasma at levels as low as 10% supplementation. At concentrations >150 μg mL-1, stealth CPNs caused ∼10% erythrocyte haemolysis, which was likely due to unbound pegylated surfactant present in the formulation. Incubation of CPNs with both whole blood and isolated platelets showed no platelet activation, increases in platelet-monocyte aggregates or induction of platelet aggregation. Interestingly, PPE-CPN formulations inhibited adenosine diphosphate (ADP)-induced platelet aggregation in a dose-dependent manner, while PPV-CPNs did not show this effect. In conclusion, stealth CPN formulations exhibiting neutrally charged, pegylated surfaces do not stimulate platelet activation or aggregation, but may induce a low degree of haemolysis in the presence of free surfactant and can inhibit physiological mediators of platelet aggregation, such as ADP.