The Crown and the Scepter: Roles of the Protein Corona in Nanomedicine

Abstract

Engineering nanomaterials are increasingly considered promising and powerful biomedical tools or devices for imaging, drug delivery, and cancer therapies, but few nanomaterials have been tested in clinical trials. This wide gap between bench discoveries and clinical application is mainly due to the limited understanding of the biological identity of nanomaterials. When they are exposed to the human body, nanoparticles inevitably interact with bodily fluids and thereby adsorb hundreds of biomolecules. A “biomolecular corona” forms on the surface of nanomaterials and confers a new biological identity for NPs, which determines the following biological events: cellular uptake, immune response, biodistribution, clearance, and toxicity. A deep and thorough understanding of the biological effects triggered by the protein corona in vivo will speed up their translation to the clinic. To date, nearly all studies have attempted to characterize the components of protein coronas depending on different physiochemical properties of NPs. Herein, recent advances are reviewed in order to better understand the impact of the biological effects of the nanoparticle–corona on nanomedicine applications. The recent development of the impact of protein corona formation on the pharmacokinetics of nanomedicines is also highlighted. Finally, the challenges and opportunities of nanomedicine toward future clinical applications are discussed.

Pheophytin Derived Near‐Infrared‐Light Responsive Carbon Dot Assembly as a New Phototheranotic Agent for Bioimaging and Photodynamic Therapy

“…DLS characterization displayed that there was no obvious difference in size distributions of CD assembly in water and PBS even prolongt ime to 7days ( Figure S4 a), indicating the satisfied water-stability of CD assembly.H owever, under physiological conditions, the sizes of approximately 160 nm of CD assembly in 1640 mediuma nd FBS are larger than that of approximately 120 nm of CD assembly in water and PBS (Figures S4 ba nd c), which is probablyd ue to the formation of protein crown. [29] Meanwhile, the smaller size below 10 nm of CDs can also be observed, suggesting the slightd isassembly of CD assembly under physiological conditions.The zeta (z) potentialo fC Di sÀ13.9 mV in water ( Figure 4d), which indicated that CD assembly have some negatively-charged functional groups on the surface. From the absorption spectrumo fC Da ssembly (Figure 4e), we still observed CD assembly have ar elatively strong absorption in NIR region,i ndicating its capability for NIR light-triggered therapy.M eanwhile, no obvious changed absorbance of CD assembly under 671 nm laser with different irradiationt imes can be observed, indicating the good photostability of CD assembly ( Figure S5).…”

“…DLS characterization displayed that there was no obvious difference in size distributions of CD assembly in water and PBS even prolong time to 7 days (Figure S4 a), indicating the satisfied water‐stability of CD assembly. However, under physiological conditions, the sizes of approximately 160 nm of CD assembly in 1640 medium and FBS are larger than that of approximately 120 nm of CD assembly in water and PBS (Figures S4 b and c), which is probably due to the formation of protein crown . Meanwhile, the smaller size below 10 nm of CDs can also be observed, suggesting the slight disassembly of CD assembly under physiological conditions.The zeta (ζ) potential of CD is −13.9 mV in water (Figure d), which indicated that CD assembly have some negatively‐charged functional groups on the surface.…”

Formation of a Monolayer Protein Corona around Polystyrene Nanoparticles and Implications for Nanoparticle Agglomeration

“…As NP‐based biomedical compounds are often designed to expose functional groups for specific interaction with biological targets, protein adsorption introduces an additional layer of complexity to their development . In recent years, however, researchers have devised strategies to control and exploit the protein corona to enable specific capabilities in biomedical applications …”

Surface chemistry governs the sub-organ transfer, clearance and toxicity of functional gold nanoparticles in the liver and kidney

“…Previous work showed that cationic GNPs had the propensity to agglomerate and be retained in the cells for a relatively long time after phagocytosis, resulting in long-term tissue accumulation [35]. "Protein corona" formation on NP surfaces considerably affects their blood circulation time, biodistribution profile, transfer, and interactions with cells [40,41]. The surface chemistry of NPs also plays an important role in regulating protein adsorption and subsequent cellular adhesion [42].…”