Volume 5 Number 1 2026
Stealth Nanocarriers with a Tunable Protein Corona to Prolong Circulation and Reduce Hepatic Clearance in Cancer Nanotheranostics
Aya Elfiki 1*
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110971
Submitted: 12 June 2026 Revised: 02 August 2026 Accepted: 11 August 2026 Published: 13 August 2026
Cancer nanotheranostics promises something clinically unusual: a single intravenous construct that reports where it has gone and treats what it finds. That promise is routinely defeated within minutes of injection. The liver, through Kupffer cell phagocytosis and sinusoidal filtration, removes 90–95% of a conventional nanocarrier dose, so the tumour sees only a residual fraction of what was administered. The decisive event occurs earlier than most design frameworks assume. On contact with plasma, a nanocarrier acquires a biomolecular corona that supersedes its synthetic surface and supplies the biological identity the mononuclear phagocyte system actually reads. This review examines how that corona can be governed rather than merely resisted. We first map the physicochemical determinants — hydrodynamic size, zeta potential, grafting conformation and interfacial elasticity — that set the balance between renal loss, tumour extravasation and hepatic capture. We then compare stealth architectures: PEGylation and its accelerated blood clearance liability, zwitterionic coatings that resist fouling without antibody induction, intrinsically disordered polypeptides, biomimetic membrane cloaking, and the emerging class of deliberately tuned coronas that recruit albumin, clusterin and apolipoproteins in place of opsonins. Evidence that protein adsorption is required for, not merely tolerated by, the stealth effect reframes the whole design objective. Reported gains are substantial — phagocytosis suppressed up to 2.6-fold, half-life extended from minutes to roughly 21 hours or, with erythrocyte membranes, several days — and translate into measurable theranostic performance across MRI-, photoacoustic- and ultrasound-guided platforms. Reproducibility, corona variability between donors and species, and manufacturing control remain the binding constraints on translation.
Keywords: protein corona; stealth nanocarrier; hepatic clearance; Kupffer cell; dysopsonin; cancer nanotheranostics; PEGylation; biomimetic membrane camouflage
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