Colapicchioni Valentina, Tilio Martina, Digiacomo Luca, Gambini Valentina, Palchetti Sara, Marchini Cristina, Pozzi Daniela, Occhipinti Sergio, Amici Augusto, Caracciolo Giulio
Istituto Italiano di Tecnologia, Center for Life Nano Science@Sapienza, Viale Regina Elena 291, 00161 Rome, Italy.
School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino (MC), Italy.
Int J Biochem Cell Biol. 2016 Jun;75:180-7. doi: 10.1016/j.biocel.2015.09.002. Epub 2015 Sep 11.
When nanoparticles (NPs) are dispersed in a biofluid, they are covered by a protein corona the composition of which strongly depends on the protein source. Recent studies demonstrated that the type of disease has a crucial role in the protein composition of the NP corona with relevant implications on personalized medicine. Proteomic variations frequently occur in cancer with the consequence that the bio-identity of NPs in the blood of cancer patients may differ from that acquired after administration to healthy volunteers. In this study we investigated the correlation between alterations of plasma proteins in breast, gastric and pancreatic cancer and the biological identity of clinically approved AmBisome-like liposomes as determined by a combination of dynamic light scattering, zeta potential analysis, one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE) and semi-quantitative densitometry. While size of liposome-protein complexes was not significantly different between cancer groups, the hard corona from pancreatic cancer patients was significantly less negatively charged. Of note, the hard corona from pancreatic cancer patients was more enriched than those of other cancer types this enrichment being most likely due to IgA and IgG with possible correlations with the autoantibodies productions in cancer. Given the strict relationship between tumor antigen-specific autoantibodies and early cancer detection, our results could be the basis for the development of novel nanoparticle-corona-based screening tests of cancer.
当纳米颗粒（NPs）分散在生物流体中时，它们会被一层蛋白质冠层覆盖，其组成很大程度上取决于蛋白质来源。最近的研究表明，疾病类型在NP冠层的蛋白质组成中起着关键作用，对个性化医疗具有重要意义。蛋白质组学变化在癌症中经常发生，结果是癌症患者血液中NP的生物特性可能与给予健康志愿者后所获得的不同。在本研究中，我们通过动态光散射、zeta电位分析、一维十二烷基硫酸钠聚丙烯酰胺凝胶电泳（1D-SDS-PAGE）和半定量密度测定法相结合，研究了乳腺癌、胃癌和胰腺癌患者血浆蛋白变化与临床批准的两性霉素B脂质体（AmBisome）类似物脂质体的生物学特性之间的相关性。虽然脂质体-蛋白质复合物的大小在癌症组之间没有显著差异，但胰腺癌患者的硬冠层带负电荷明显较少。值得注意的是，胰腺癌患者的硬冠层比其他癌症类型的更丰富，这种丰富很可能是由于IgA和IgG，可能与癌症中的自身抗体产生有关。鉴于肿瘤抗原特异性自身抗体与癌症早期检测之间的密切关系，我们的结果可能成为开发基于新型纳米颗粒冠层的癌症筛查测试的基础。
