Nanotechnology · evidence and evaluation

What a coating changes, and why the surface is usually the variable that moved

A ligand or coating changes what the outside of a particle is, which is what solvents, cells and other particles actually meet. In a biological medium the engineered surface is quickly covered by adsorbed proteins, so the particle acquires a second identity the designer did not specify.

How it works

Functionalisation is normally introduced as a way to control dispersion, stability and targeting, and it does all of those things. But the review by Akhter and colleagues describes what happens next in a biological medium: proteins adsorb rapidly and form a corona, and the cell encounters that corona rather than the surface that was designed. The composition depends on size, shape, surface charge and surface chemistry as well as the medium, and it evolves in time — abundant proteins arrive first and are displaced by higher-affinity ones. The review separates a tightly bound hard corona, whose exchange time exceeds the cellular uptake it competes with, from a loosely bound soft corona that exchanges freely. The consequence it reports for engineered targeting is blunt: the functional characteristics of ligated particles can be cloaked, and they may lose their targeting potential. Maha’s point for a reader comparing two samples is narrower and applies outside biology too — when a coating changes, the surface chemistry, the effective size and the aggregation behaviour usually change with it, so a comparison that varies coating alongside size has varied at least two things.

A concrete case

Two batches of the same core material are compared, one bare and one ligand-functionalised, and the functionalised batch performs better in a cell assay. That result is consistent with the ligand working as intended, and equally consistent with a different corona forming, a different effective hydrodynamic size, and a different aggregation state. Nothing in the comparison separates them.

What this establishes

That the engineered surface is not necessarily the surface that acts, that corona composition is governed by properties the designer does control, and that a targeting ligand can be functionally hidden by what adsorbs on top of it.

What it does not

A review of reported findings, mostly in serum and cell-culture systems. It does not tell you the corona for any particular product, does not predict a clinical result, and is not evidence that any nanomedicine works or is safe. Outside biology the corona mechanism does not apply, though the confounding of coating with size and aggregation still does.

Questions worth asking

  • Ask whether the coating was the only thing that changed between the samples being compared, and how that was established.
  • Ask what medium the particles were measured in, and whether size was measured in that medium or in a clean solvent.
  • For a targeting claim, ask what evidence exists that the ligand is still exposed and functional after exposure to the biological medium.
  • Treat “functionalised” as a description of an intended synthesis step, not as a measurement of the surface that resulted.

Sources

  • Akhter et al. — Impact of Protein Corona on the Biological Identity of Nanomedicine: Understanding the Fate of Nanomaterials in the Biological Milieu (Biomedicines, 2021) ↗

    Nanoparticles entering a biological medium rapidly adsorb proteins, forming a corona that the cell encounters instead of the engineered surface — a biological identity distinct from the synthetic one. Composition depends on particle size, shape, surface charge and surface chemistry as well as the medium, and adsorption is time-dependent, abundant proteins arriving first and being displaced by higher-affinity ones. The review distinguishes a tightly bound hard corona, whose exchange time exceeds cellular uptake, from a loosely bound soft corona that exchanges freely, and reports that ligand-functionalised particles can have their targeting function cloaked by the corona and lose targeting potential.

    Boundary: A review of reported findings, largely in serum and cell-culture systems. It does not establish the corona composition for any particular product, nor predict a clinical outcome, and it is not evidence that any nanomedicine is safe or effective.

    Locator, anchor and reuse basis

    Read at: Introduction; “Types of Coronas and the Biological Identity of NPs”; “Impact on the Physico-Chemical Characteristics”; “Drug Targeting and Cellular Uptake in the Biological Milieu”. Inspected 2026-09-20. Open-access review; paraphrased and linked, with short attributed wording only.

    Verify by searching the source for: an NP–protein complex called protein corona. If that phrase is not there, or does not carry the meaning stated above, this citation is wrong and we want to know.

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Maha Strategies publishes explanation and evaluation method. We make no nanomaterials, run no characterisation, certify nothing, and give no medical or legal advice.