Most common issues

Mechanism of detection  Access to cytosol Calibration Limit of detection Endosomal escape
Rationale Justification Validation Translation
Data Mentioned but not shown Data provided but they do not support the conclusions Lack of evidence that could support the conclusions
Figures Values or units Similarity Duplication Resolution Label
Methodology Materials preparation Characterization
Characterization DLS TEM
Cell lines Confluency Lack of control
Use of scientific terms Inaccurate
References Miscitation No citation Primary sources Citation error

Specification of the common issues

Articles lacking a discussion of endosomal escape

             In the field of bionanoscience, several articles report the use of nanoparticles for intracellular sensing (viz. mRNAs, various ions, pH changes, and others). However, nanoparticles generally enter the cell by endocytosis. Many of those publications lack an explanation about the internalisation mechanism, and, crucially, endosomal escape. Indeed, to achieve the purpose of detection of cytosolic targets inside cells, the nanoparticles must escape the endosomes. In most articles that we have analysed so far this issue is ignored.

Here you can find a list of our comment on articles that report intracellular sensing with nanoparticles but do not discuss the endosomal escape of the nanomaterials.

Mechanisms of detection

Access to cytosol

The article claims the intracellular localisation of nanoparticles, but there is no mention of the mechanism of uptake through which the nanomaterials enter the cells.


Lack of calibration or calibration that raises questions (e.g. binding equilibrium does not follow what would be expected from thermodynamics).

Limit of detection

LOD is not calculated; or the experiments or calculations raise questions.

Endosomal escape

There is no proof of nanomaterials endosomal escape.



An explanation for justifying the necessity of the work is missing.


The data presented does not validate the claimed achievements or the methodology applied.


The work is presented as useful tool for certain purposes, e.g., diagnosis. However, the limitations for translating the methods “from the bench” to the application itself is not stated.


Mentioned but not shown

Some techniques are mentioned in the methodology or results, but the data are not shown in the full text, nor in the supporting information.

Data provided but they do not support the conclusions

Lack of evidence that could support the conclusions


Values or units                                                                                                                                                              

The units or values of X-axis and Y-axis are not shown.

The values in the axis do not match the ticks.


Data from different samples or conditions are more similar than would be expected.


Image duplication for different conditions detected within the article or across publications.

Magnification and resolution

The magnification or resolution is too low to draw conclusions, e.g. on precise intracellular localisation of nanoparticles.


Errors in the text of the labels or confusing definitions.


Materials preparation

Reproducing the experiments would be difficult because specifications are missing regarding the preparation or procurement of materials.


Characterization of materials is incomplete or lacking.

Nanoparticles size


When claiming the nanoparticles hydrodynamic diameter, for more precise conclusions we suggest the following issues to be corrected:

    • The size distribution is not shown.
    • The average size of multimodal data is reported. In such cases, the discussion should make clear that different size populations were observed, and state the average of each population, not of the sample.
    • It is not clear whether the distribution represents the intensity of light, number or volume of particles. (For more precise claiming of the nanomaterials size, this should be indicated, because many times only one population of particles is seen in the number or volume data, but actually the intensity shows a multimodal distribution. Further, number and volume can only be considered when the quality of the data are adequate, which means good correlation function and low PdI. For more information, please check Intensity-Volume-Number: Which size is correct?. Please note this comes from a company, and additional references will be provided as soon as possible).


The physical size is given, but the distribution is not provided and there is no detail about the statistics.

The physical size is given but only a few nanoparticles can be seen in the micrographs.

The stability of the nanomaterials is claimed but aggregates are present in the micrographs.

Cell lines

Lack of control

Control experiments are missing, for example, to prove specificity or demonstrate lack of toxicity.

Use of scientific terms


Established terms used in a different way from their normal use.

Replacing established terms in the literature by confusing definitions.


An exaggeration of the claims, results and relevance of the work is made without being adequately justified, usually supported by words as ‘exceptional’, ‘the best material’, ‘we report a new method’, ‘high sensitivity’, ‘significant enhancement’, and others.



The citation is not related to or does not support the claim. In some cases the citation supports an idea or fact opposite to what it is stated in the publication we are analysing.

No citation

An important claim is made mentioning sentences as “previous works” or “it is discussed” but no reference is cited at the end of the sentence.

Primary sources

Reviews or other secondary sources are cited instead of the original work.

Citation error

The cited work is from an author different from the one mentioned in the text.

Other remarks                                                                                                                                                             

The concerns which are not classified in the grid, but still relevant according to us.

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