卵巢癌患者血浆蛋白冠的形成及其对纳米粒靶向性的影响

纳米制剂进入体内环境后,可以自发地吸附血液中的蛋白质等生物大分子形成蛋白冠,并影响其在体内的预期功能.在不同的生理状态下,血浆蛋白的种类和含量不同,形成蛋白冠后对纳米粒的影响也不同.为此,本研究合成了叶酸(FA)修饰的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒(PLGA-FA),以仅有聚乙二醇(PEG)修饰的纳米粒(PL...

Preparation and targeting capability of corona forming in human ovarian plasma

After entering the physiological environment,proteins and other biomolecules bind to the nanoparticles’surface,called protein corona.The corona establishes a new bio-interface that affects its physicochemical properties and biological behaviors.Variations in types and contents of human plasma proteins during the different physiological states can substantially change the composition and effects of the corona.With folic acid(FA)-modified polylactic acid-polyglycolic acid copolymer(PLGA)nanoparticles,the formation of protein coronas and their influence on the targeting capability are studied in healthy and ovarian human plasma.All human plasma samples were collected at the Peking University Third Hospital and this study protocol has been approved by Peking University Third Hospital Medical Science Research Ethics Committee(2019-409-1).Dynamic light scattering measurements demonstrated a 10-40 nm increase in their size distributions and a 30 mV decreased in their absolute zeta-potential since protein corona-coated PLGA-PEG and PLGA-FA were formed.The SDS-PAGE analysis showed the composition of the protein coronas from ovarian and healthy plasma in PLGA-FA were markedly distinct,particularly for proteins with molecular weight of 45,110 and>180 kDa.Flow cytometry indicated that the absorption of ovarian plasma in PLGA-FA led to a lower cellular uptake by SKOV3 cells.Our results suggest that in vitro formed ovarian plasma protein corona could shield targeting molecules and reduced receptor-mediated internalization.The results of this pilot study will provide evidence of the effectiveness of active targeting nanoparticles under pathologic conditions.Additionally,the protein corona in different diseases is emerging as a key point;thus,a comprehensive understanding could accelerate clinical translation of functionalized nanoparticles.