Sirazum Munira, Abdelfattah Ahmed, Pandey Prashant, Ashkarran Aliakbar, Tadjiki Soheyl, Sharifi Shahriar, Gharibi Hassan, Saei Amir Ata, Mahmoudi Morteza, Lavasanifar Afsaneh
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta Edmonton Alberta T6G 2E1 Canada
Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University Assiut 71526 Egypt.
Nanoscale Adv. 2025 Jun 23. doi: 10.1039/d4na01085j.
Protein corona formation on nanoparticles affects their biological interactions and fate. Polymeric micelles (PMs), preferred nanocarriers for poorly water-soluble drugs, have unclear behaviors in biological environments. This study examines the protein corona compositions of PMs formed from poly(ethylene oxide)--poly(ε-caprolactone) (PEO-PCL) and PEO--poly(α-benzyl carboxylate-ε-caprolactone) (PEO-PBCL) copolymers with varying degrees of polymerization after incubation in human plasma, and explores their relationship with cellular uptake by colorectal cancer cells. Traceable block copolymers were synthesized, self-assembled into PMs (44-99 nm, slightly negative zeta potentials), and characterized. Protein coronas were formed by incubating PMs with human plasma; protein-coated micelles were separated and analyzed. Uptake of selected PMs, with and without human plasma pre-incubation, by colorectal cancer cells was assessed. PEO-PCL micelles exhibited higher cellular uptake than PEO-PBCL micelles. Human plasma significantly reduced the uptake of PEO-PCL micelles, while PEO-PBCL micelles' uptake remained low. Proteomic analysis identified 23 distinct proteins among the combined top 20 most abundant proteins from each PM corona, with 18 common across all micelle types. In the top 10 proteins, PEO-PCL micelles shared an identical profile, whereas PEO-PBCL micelles had two unique proteins not present in PEO-PCL coronas. Protein corona composition in both PMs was shown to influence their cellular uptake behavior.
纳米颗粒上蛋白质冠层的形成会影响其生物相互作用和命运。聚合物胶束（PMs）是水溶性差的药物首选的纳米载体，其在生物环境中的行为尚不清楚。本研究检测了由聚（环氧乙烷）-聚（ε-己内酯）（PEO-PCL）和聚（环氧乙烷）-聚（α-苄基羧酸酯-ε-己内酯）（PEO-PBCL）共聚物在不同聚合度下于人类血浆中孵育后形成的PMs的蛋白质冠层组成，并探讨了它们与结肠癌细胞摄取之间的关系。合成了可追踪的嵌段共聚物，将其自组装成PMs（44-99nm，zeta电位略为负值）并进行表征。通过将PMs与人类血浆孵育形成蛋白质冠层；分离并分析蛋白质包被的胶束。评估了结肠癌细胞对选定的经人类血浆预孵育和未经预孵育的PMs的摄取情况。PEO-PCL胶束比PEO-PBCL胶束表现出更高的细胞摄取率。人类血浆显著降低了PEO-PCL胶束的摄取率，而PEO-PBCL胶束的摄取率仍然较低。蛋白质组学分析在每种PM冠层中最丰富的前20种蛋白质中总共鉴定出23种不同的蛋白质，所有胶束类型中有18种是共有的。在前10种蛋白质中，PEO-PCL胶束具有相同的图谱，而PEO-PBCL胶束有两种独特的蛋白质不存在于PEO-PCL冠层中。两种PMs中的蛋白质冠层组成均显示会影响其细胞摄取行为。
