Bypassing Protein Corona Issue on Active Targeting: Zwitterionic Coatings Dictate Specific Interactions of Targeting Moieties and Cell Receptors

Abstract

Surface functionalization strategies for targeting nanoparticles (NP) to specific organs, cells, or organelles, is the foundation for new applications of nanomedicine to drug delivery and biomedical imaging. Interaction of NPs with biological media leads to the formation of a biomolecular layer at the surface of NPs so-called as "protein corona". This corona layer can shield active molecules at the surface of NPs and cause mistargeting or unintended scavenging by the liver, kidney, or spleen. To overcome this corona issue, we have designed biotin-cysteine conjugated silica NPs (biotin was employed as a targeting molecule and cysteine was used as a zwitterionic ligand) to inhibit corona-induced mistargeting and thus significantly enhance the active targeting capability of NPs in complex biological media. To probe the targeting yield of our engineered NPs, we employed both modified silicon wafer substrates with streptavidin (i.e., biotin receptor) to simulate a target and a cell-based model platform using tumor cell lines that overexpress biotin receptors. In both cases, after incubation with human plasma (thus forming a protein corona), cellular uptake/substrate attachment of the targeted NPs with zwitterionic coatings were significantly higher than the same NPs without zwitterionic coating. Our results demonstrated that NPs with a zwitterionic surface can considerably facilitate targeting yield of NPs and provide a promising new type of nanocarriers in biological applications.

Investigating in vitro and in vivo αvβ6 integrin receptor-targeting liposomal alendronate for combinatory γδ T cell immunotherapy

“…Recent studies have revealed that the formation of a protein corona on the surface of liposomes can lead to an inhibition of targeting efficacy, as the targeting-peptides can be hidden from their receptors [40], [41], [42], [43]. We have therefore conducted a study to see if incubation of t-L-ALD with mouse serum will compromise the targeting efficiency, in an attempt to correlate the in vitro targeting efficiency with in vivo active targeting in a living mouse.…”

Towards clinically translatable in vivo nanodiagnostics

“…For example, corona-free nanoparticles were developed with tunable hydrophobicity that serve as platforms to enhance desirable nanobiological behaviour, such as cellular uptake and haemolysis 137 . In addition, silica nanoparticles conjugated with biotin and cysteine were introduced to suppress corona-associated mistargeting, wherein cysteine was used as a zwitterionic ligand 138 . In this study, it was reported that a zwitterionic surface aids targeting.…”

Particle Targeting in Complex Biological Media

“…[109] www.advancedsciencenews.com www.advhealthmat.de particles. [118,122] Particles functionalized with zwitterionic cysteine and biotin showed reduced protein adsorption, and biotin-mediated cell uptake after incubation with HP was higher than for targeted particles without the zwitterionic coating. [118] Strategies and opportunities for tuning the protein corona on the carrier surface with regard to the performance of an active-targeting drug carrier will be discussed in detail in the next section.…”