Predictors of cellular uptake efficiency in preclinical animal models with bacterial infections

Ying Zhou; W. Huang; W. Xu

doi:10.5281/zenodo.22811896

Authors

Ying Zhou Department of Clinical Nanomaterials Science, Danube Institute for Advanced Nanomaterials Science Author https://orcid.org/7258-9875-1144-1917
W. Huang Department of Nanomaterials Science, Indus Institute for Advanced Nanomedicine Author https://orcid.org/2587-7191-5169-308X
W. Xu Department of Clinical Nanomaterials Science, Indus Institute for Advanced Nanomedicine Author https://orcid.org/0941-7446-2559-7387

DOI:

https://doi.org/10.5281/zenodo.22811896

Keywords:

cellular uptake, nanoparticle, bacterial infection, protein corona, biofilm

Abstract

Graphical abstract

Background: Nanoparticle carriers designed for bacterial infection often show strong cellular uptake in serum-free culture but far weaker performance in an infected animal, a gap driven by predictors that interact rather than act independently.

Objective: This review synthesizes evidence on what predicts nanoparticle cellular uptake efficiency in preclinical bacterial infection models, spanning size, charge, shape, protein corona formation, and the biofilm barrier unique to infection.

Methods: We conducted a narrative synthesis of foundational biophysical uptake studies and infection-specific studies of nanoparticle transport in murine and biofilm models.

Findings: Uptake peaks at an intermediate size rather than scaling monotonically [4]; cationic charge advantages seen in serum-free medium are often reversed once a protein corona assembles within seconds of blood contact [9,12]; shape governs phagocytic capture by macrophages harboring intracellular bacteria [13]; and biofilm matrix acts as a size- and charge-selective barrier absent from single-cell assays [19,20].

Conclusions: Uptake in bacterial infection models is best predicted by size, corona-modified charge, shape, and matrix-penetration considered jointly; infection-microenvironment-responsive coatings offer a demonstrated route to preserving uptake despite these confounds [21,22].

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