title: 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.
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University , Tehran, Iran.
authors.forename: Reihaneh
authors.initials: R
authors.lastname: Safavi-Sohi
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University , Tehran, Iran.
authors.forename: Shokoofeh
authors.initials: S
authors.lastname: Maghari
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran.|Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems , Heisenbergstraße 3, D-70569 Stuttgart, Germany.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Raoufi
authors.affiliation: Department of Immunology, Shahid Beheshti University of Medical Science , Tehran, Iran.
authors.forename: Seyed Amir
authors.initials: SA
authors.lastname: Jalali
authors.affiliation: Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences , Bushehr, Iran.
authors.forename: Mohammad J
authors.initials: MJ
authors.lastname: Hajipour
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University , Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ghassempour
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran.|Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Morteza
authors.initials: M
authors.lastname: Mahmoudi
mesh_terms: D016503:Drug Delivery Systems; D006801:Humans; D050997:Nanomedicine; D053758:Nanoparticles; D000066970:Protein Corona / Q000737:chemistry*; D012822:Silicon Dioxide
chemical_list: D000066970:Protein Corona; D012822:Silicon Dioxide
keywords: active targeting; cellular uptake; engineered nanoparticles; protein corona; surface chemistry; zwitterionic coatings