Sex-Specific Silica Nanoparticle Protein Corona Compositions Exposed to Male and Female BALB/c Mice Plasmas

Abstract

As various nanoparticles (NPs) are increasingly being used in nanomedicine products for more effective and less toxic therapy and diagnosis of diseases, there is a growing need to understand their biological fate in different sexes. Herein, we report a proof-of-concept result of sex-specific protein corona compositions on the surface of silica NPs as a function of their size and porosity upon incubation with plasma proteins of female and male BALB/c mice. Our results demonstrate substantial differences between male and female protein corona profiles on the surface of silica nanoparticles. By comparing protein abundances between male and female protein coronas of mesoporous silica nanoparticles and Stober silica nanoparticles of ∼100, 50, and 100 nm in diameter, respectively, we detected 17, 4, and 4 distinct proteins, respectively, that were found at significantly different concentrations for these constructs. These initial findings demonstrate that animal sex can influence protein corona formation on silica NPs as a function of the physicochemical properties. A more thorough consideration of the role of plasma sex would enable nanomedicine community to design and develop safer and more efficient diagnostic and therapeutic nanomedicine products for both sexes.

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“…This protein corona is a primary driver of nanoparticle distribution and elimination, mediating both desired interactions (such as uptake of the nanoparticle by target cells) as well as undesired interactions (such as nanoparticle opsonization by circulating immune cells) (Tran and Roffler, 2023). Ashkarran and others concluded that protein corona composition was distinct for silica nanoparticles exposed to female versus male mouse plasma (Ashkarran et al, 2023), which may be a critical finding for the field. However, it should be noted that their results are reported from experiments involving plasma that was pooled from 3 female versus 3 male mice, yielding a single sample of plasma for each sex.…”

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“…For instance, depending on the biological sex, LNPs may undergo different processing, encountering unique biological environments associated with each biological sex. Indeed, biological sex-dependent protein corona formation has been reported [ 27 ], suggesting that the biological sex of the host could impact the interaction between LNPs and proteins in the body. Any differences in the protein corona may change LNP surface properties, which in turn could impact cellular uptake and the processing of LNPs and, hence, affect biodistribution, clearance, and expression profiles [ 28 , 29 , 30 , 31 ].…”

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