Protein‐Corona‐by‐Design in 2D: A Reliable Platform to Decode Bio–Nano Interactions for the Next‐Generation Quality‐by‐Design Nanomedicines. Issue 40 (24th August 2018)

• Record Type: Journal Article
• Authors: Mei, Kuo‐Ching; Ghazaryan, Artur; Teoh, Er Zhen; Summers, Huw D.; Li, Yueting; Ballesteros, Belén; Piasecka, Justyna; Walters, Adam; Hider, Robert C.; Mailänder, Volker; Al‐Jamal, Khuloud T.
• Is Part Of: Advanced materials. Volume 30:Issue 40(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-08-24
• Subjects: click chemistry -- drug delivery -- graphene -- nanomedicine -- protein corona -- toxicity; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.201802732
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: Hard corona (HC) protein, i.e., the environmental proteins of the biological medium that are bound to a nanosurface, is known to affect the biological fate of a nanomedicine. Due to the size, curvature, and specific surface area (SSA) 3‐factor interactions inherited in the traditional 3D nanoparticle, HC‐dependent bio–nano interactions are often poorly probed and interpreted. Here, the first HC‐by‐design case study in 2D is demonstrated that sequentially and linearly changes the HC quantity using functionalized graphene oxide (GO) nanosheets. The HC quantity and HC quality are analyzed using NanoDrop and label‐free liquid chromatography–mass spectrometry (LC‐MS) followed by principal component analysis (PCA). Cellular responses (uptake and cytotoxicity in J774 cell model) are compared using imaging cytometry and the modified lactate dehydrogenase assays, respectively. Cellular uptake linearly and solely correlates with HC quantity ( R 2 = 0.99634). The nanotoxicity, analyzed by retrospective design of experiment (DoE), is found to be dependent on the nanomaterial uptake (primary), HC composition (secondary), and nanomaterial exposure dose (tertiary). This unique 2D design eliminates the size–curvature–SSA multifactor interactions and can serve as a reliable screening platform to uncover HC‐dependent bio–nano interactions to enable the next‐generation quality‐by‐design (QbD) nanomedicines for better clinical translation. Abstract : The Protein corona is of tremendous interest in the nanomedicine field. A 2D nanographene platform (2D graphene oxide) is presented to orchestrate quality by design (QbD) protein corona profiles. Protein analyses correlated with nanomaterial uptake and cytotoxicity studies provide new insights into the nanostructure‐and‐activity relationship (NanoSAR) and QbD nanomedicines.