Achieving a stealth effect of nanocarriers through controlled protein adsorption
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Abstract
Drug delivery by nanocarriers has evolved into a momentous field of interdisciplinary research. A crucial aspect for the success of any form of future nanotherapeutic is the protein corona, which forms around the surface of a nanocarrier immediately once it enters a bodily fluid like blood plasma. Certain apolipoproteins in this corona are responsible for the ‘stealth effect’, i.e. the non-uptake of a nanocarrier by phagocytes and a resulting long blood circulation time. The aim of controlled biological behavior through a defined ‘stealth’ protein corona was approached from different sides in this work.
Firstly, with the physical adsorption of poly(phosphoester) surfactants a new approach to the stealth effect of polystyrene nanoparticles was introduced to facilitate and generalize the stealth functionalization strategy. A similar composition of the protein corona as for nanocarriers with poly(ethylene glycol) chains grafted to their surface could be observed. Cellular uptake experiments confirmed a stealth effect for the surfactant-coated nanoparticles.
Afterwards, the role of lipids for the formation of a stealth corona and the consequences for cellular uptake were investigated. Lipoprotein adsorption to nanoparticles was analyzed with various methods and new insights into the mechanism of the interaction with nanoparticles could be gained. Evidence for the disintegration of lipoprotein complexes upon adsorption was found. Moreover, denaturation of important stealth corona proteins by surfactants was analyzed with complementary methods. In this context, the effect of additional cetyltrimethylammonium chloride on the composition of the protein corona was studied and a clear shift could be observed. Two selected apolipoproteins were screened for their sensitivity to surfactant denaturation and significant differences were found. Further, a possible influence of heat inactivation on the folding state and adsorption behavior of proteins was investigated. Finally, the commonly used stealth polymer poly(ethylene glycol) has been tested for possible interaction with proteins.
In conclusion, new findings on the complex interactions of nanoparticle formulations with single proteins and blood plasma could be gained and the potential influence of surfactants could be illuminated. The results gained in this work provide valuable knowledge for future research on this subject.