Strategy for Avoiding Protein Corona Inhibition of Targeted Drug Delivery by Linking Recombinant Affibody Scaffold to Magnetosomes

Abstract

Purpose: Nanoparticles (NPs) decorated with functional ligands are promising candidates for cancer diagnosis and treatment. However, numerous studies have shown that chemically coupled targeting moieties on NPs lose their targeting capability in the biological milieu because they are shielded or covered by a "protein corona". Herein, we construct a functional magnetosome that recognizes and targets cancer cells even in the presence of protein corona. Methods: Magnetosomes (BMPs) were extracted from magnetotactic bacteria, M. gryphiswaldense (MSR-1), and decorated with trastuzumab (TZ) via affibody (RA) and glutaraldehyde (GA). The engineered BMPs are referred to as BMP-RA-TZ and BMP-GA-TZ. Their capacities to combine HER2 were detected by ELISA, the quantity of plasma corona proteins was analyzed using LC-MS. The efficiencies of targeting SK-BR-3 were demonstrated by confocal laser scanning microscopy and flow cytometry. Results: Both engineered BMPs contain up to ~0.2 mg TZ per mg of BMP, while the quantity of HER2 binding to BMP-RA-TZ is three times higher than that binding to BMP-GA-TZ. After incubation with normal human plasma or IgG-supplemented plasma, GA-TZ-containing BMPs have larger hydrated radii and more surface proteins in comparison with RA-TZ-containing BMPs. The TZcontaining BMPs all can be targeted to and internalized in the HER2-overexpressing breast cancer cell line SK-BR-3; however, their targeting efficiencies vary considerably: 50-75% for RA-TZ-containing BMPs and 9-19% for GA-TZ-containing BMPs. BMPs were incubated with plasma (100%) and cancer cells to simulate human in vivo environment. In this milieu, BMP-RA-TZ uptake efficiency of SK-BR-3 reaches nearly 80% (slightly lower than for direct interaction with BMP-RA-TZ), whereas the BMP-GA-TZ uptake efficiency is <17%. Conclusion: Application of the RA scaffold promotes and orients the arrangement of targeting ligands and reduces the shielding effect of corona proteins. This strategy improves the targeting capability and drug delivery of NP in a simulated in vivo milieu.

Hybrid Nanosystems of Antibiotics with Metal Nanoparticles—Novel Antibacterial Agents

“…In the case of carbohydrate-decorated amphiphilic nanoparticles, a protein crown is formed in the biological environment based mainly on human serum albumin, complement proteins, apolipoproteins, and proteins involved in the coagulation cascade. Although the presence of these protein crowns significantly reduced the cellular uptake of amphiphilic assemblies, they also significantly reduced the cytotoxic and hemolytic effects resulting from the contact of NPs with living cells [ 129 ]. The ability to control protein corona formation with ligand molecules has been used to regulate the intracellular activation of nanoenzymes through endosomal proteolysis of coronal proteins [ 130 ].…”

Overview of Physicochemical Properties of Nanoparticles as Drug Carriers for Targeted Cancer Therapy

“…Careful modulation of the protein corona through the tuning of intrinsic and extrinsic parameters may allow nanoparticles to be delivered optimally in tumor tissue [ 72 ]. A study [ 73 ] has shown that linking Z domain-based recombinant affibody (RA) scaffolds to magnetosomes (BMPs), which were then preadsorbed on anti-HER2 humanized mAb (TZ) and incubated with human plasma, resulted in the more effective targeting capability and drug delivery of nanoparticles in a simulated in vivo environment by incorporating the majority of TZ molecules into the nanoparticle–corona complex. It is also crucial to consider external factors, such as temperature, pH, and shear stress, for developing a more efficient protein corona [ 74 ].…”

Multivalent ACE2 engineering—A promising pathway for advanced coronavirus nanomedicine development

“… [236] , [238] , [239] , [240] , [245] , [246] The resulting impact may be complementary or deleterious [247] , [248] , [249] and thus worth examining for appropriate interventions. We anticipate that existing nanoparticle dispersion and stabilization strategies that leverage a careful control of the biophysical properties of phase formations and have been previously demonstrated in other protein-nanoparticle formulations [250] , [251] , [252] , [253] will be useful in circumventing protein corona and colloidal stability challenges in ACE2-based nano-pharmaceuticals. All the same, clinical safety validations of these approaches would determine their approval into clinical use.…”