Mild metabolic imbalances rewiring the protein corona dictate albumin nanoparticle mechanics, cellular processing, and in vivo trafficking
Evgeniya R. Denisova a, Maya V. Voronina a, Daria S. Volkova a, Dmitry Kostyushev b,c,d,e, Andrey A. Zamyatnin Jr. e,f, Marina V. Serebryakova g, Andrey V. Zvyagin a, Yan Wang h, Neng Yan h, Veronika A. Dimitreva i, Anton V. Zalygin i, Elena N. Subcheva a, Sabrina Bianco j,k, Michele Costanzo k,l, Armando Cevenini k,l, Lyubov V. Krylova a,m, Alessandro Parodi a,e
a Scientific Center for Translation Medicine, Sirius University of Science and Technology, 354340 Sirius, Russia
b Department of biotechnology, Sechenov University;
c Laboratory of genetic technologies in drug development, Sechenov University;
d Engelhardt Institute of Molecular Biology, RAS;
e Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234
f Department of Biological Chemistry, Sechenov First Moscow State Medical University, Moscow, 119991, Russia.
g Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.
h School of Environmental Studies, China University of Geosciences, Wuhan 430074, China.
i Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
j Department of Experimental and Clinical Medicine, University of Catanzaro Magna Græcia, Viale Europa, 88100 Catanzaro, Italy
k CEINGE – Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy
l Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy
m Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia, Gagarin Avenue, 23
Abstract
Mild, transient metabolic imbalances are common in vivo but are rarely considered in nanomedicine design. Here, we examine how moderate hyperglycemia and dehydration reshape the protein corona (PC) of albumin nanoparticles (ANPs) and influence their mechanics, cellular processing, and biodistribution. ANPs were incubated ex vivo with sera from control, glucose‑treated, or water‑deprived mice to generate distinct PCs, which were analyzed by proteomics, biophysical characterization, and functional assays. Both challenges preserved the core corona architecture but induced condition‑specific quantitative remodeling that softened ANPs, altered uptake in fibroblasts and macrophages, and differentially affected lysosomal abundance and acidification. In healthy mice, these metabolically imprinted coronas shifted ANP distribution away from a liver‑dominated profile toward enhanced, condition‑dependent accumulation in spleen and kidney both in healthy and pathological conditions (acute inlammatory injury). These data show that even mild metabolic fluctuations can fine‑tune PC composition and downstream nano–bio interactions, adding a relevant layer of variability in organ targeting while offering a simple, noncovalent handle to bias nanocarrier biodistribution.
Speaker
Alessandro Parodi
Sirius University ofd SCience and Technology
Russia
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