50 Matching Annotations
  1. Apr 2020
    1. and (right) plotting of spontaneous beating based on bright field video with time

      This does not say if the curves are for the patch or the beams, nor to what extent it is robust and reproducible.

    2. . (A) Basic motion program and (B,C) our customized ITOP system containing three components for bioprinting cardiac tissues.

      I find it quite hard to understand exactly what has been done from this figure.

    3. This is the first article we are going to discuss in 3DbioNet's online journal club. https://twitter.com/3DbioNet/status/1244670405534679040

      The article is about a 3D model of cardiac tissue using 3D bioprinting of rat cells ("neonatal rat ventricular cardiomyocytes"). The hope/promise is applications in heart transplantation (how realistic is that?) and in vitro "modeling" (for testing cardiac toxicity of drugs?).

      The 3D system was in a patch form or a string form.

    1. In order to prove the concept of exogenous GalNAc-specific iLNP targeting in wild-type mice, it was necessary to first inactivate the endogenous apoE-based targeting mechanism for iLNPs

      Is that really the best proof of principle available?

    2. Exogenous targeting

      Nice experiment. Slightly philosophical point maybe, but does "rescuing activity" (which would occur without doing anything in a normal animal, these particles) really "exogeneous targeting".

    3. Figure 3. Loss of LDLR impairs iLNP activity in vitro and in vivo

      This is quite strange. One would expect that removing the receptor would reduce binding, but here the main effect seems to be not on binding to the membrane but to uptake.

    4. ∼80%

      80% silencing with LNPs

    5. Figure 1

      The presentation in Fig 1c is relative to no ApoE. It gives the impression that iLNP is hugely better that cLNP but that is not the case as 1b shows.

  2. Mar 2020
    1. The Power of Spheres

      This "article" is in fact an advertorial, i.e. paid for content. It looks like a scientific article but is not peer reviewed. And it does not include declarations of conflict of interest even though the first author is a founder of a company that develop therapies based on the technology advertised in this feature.

  3. Nov 2019
    1. in Figure 1A,B: (I) The NP reaches the membrane surface via diffusion. (II) The NP diffuses over the water–membrane interface

      In fact, in the simulation a potential is applied to drive the particles towards the membrane so neither (I) nor (II) can be described as free diffusion.

  4. Oct 2019
    1. Based on the values of the partition function as well as the difference in time scale between the leakage process and the entry process (seconds or minutes vs nanoseconds), we assume that a steady-state condition is rapidly reached. Therefore, by comparing eq 5 with eq 4, we find that

      These words are confusing. If they assume that I(t) is proportional to [GDQ]m then equations 4 and 5 are simply identical with two different notations. I can see no reasonable reason to assume that though.

  5. Sep 2019
    1. c is a constant that depends on

      How does it depends on these things? How can the authors compare experimental results to theory without explaining this information?

    2. the fraction of particles that go outside the membrane when leaving the membrane

      what the hell is this? I would assume 100% by definition.

    3. the GQD concentration inside the vesicle and the bilayer

      "inside the bilayer" and "inside the vesicle" are two different things.

    4. 2 to 8

      "2 to 8 nm" is a huge range given; the range covered by figure 5 does not extend beyond 2.5 nm. One can guess that the probability of a low density lipid fluctuation extending over 8 nm is essentially zero.

    5. biosensing

      Nothing to do with interactions of NPs with membranes.

    6. biolabeling

      Ref 6 (2013) does not demonstrate wide use in biolabelling. It is a synthesis and proof of principle paper. 6 years later, no biologist are using these materials for their imaging needs. However there are tons more of papers about the "emerging" carbon nanomaterials for imaging. The paper has a figure about uptake in cells. It says nothing about the mechanisms of uptake and it is not possible to conclude from the data provided.

    7. wound disinfection

      Carbonaceous NPs are not widely used in wound disinfection. This 2014 paper propose the idea and doing experiments on bacteria and on mice. It contains very little about interaction of the NPs with cells.

    8. cancer therapy

      "widely used in cancer therapy" I know that this kind of poetic license is common in scientific writing but it is nevertheless wrong. Carbonaceous NPs have not been used in cancer therapy. Those two references are materials synthesis papers that claim that they could be used in the future for this purpose. Reference 5 is about pegylated graphene oxide which is fundamentally different from anything modelled here (and the PEG is to make it water soluble). Reference 5 also concludes the nanoparticles enter by endocytosis.

    9. like drug delivery

      Reference 2 is a paper about micron-size particles that can be opened by ultrasounds. It does not have any experiments with membranes nor living things. Reference 3 is mostly a materials synthesis and characterization paper. The little it has about interaction with cells, figure 8 and 9, concludes unambiguously that the particles enter by endocytosis, i.e. nothing to do with the kind of mechanisms modelled in this paper. Reference 4 is about particles which are ~75 nm diameter so very different from the materials modelled in this paper. Like for Ref 3, the paper concludes unambiguously that entry into the cells is by endocytosis (that's even visible from TOC visual abstract).

    10. KD is estimated by using the approach outlined in ref

      Why are the values of Kd not given anywhere in this paper?

    11. Figure 9. Measured GQD leakage from different lipid vesicles. (A) Experimental images of photoluminescence change over a 1 h period. Images were taken every 15 min. White scale bar is 50 μm. (B) Photoluminescence intensity over a 1 h period for GQD-encapsulated vesicles with different lipid compositions is indicated. (C) Comparison of the model’s predictions to the permeability measured from experiment (error bars correspond to one standard deviation).

      The partition coefficient tell us that it should be 100% in the membrane (see table 1). Why don't we see any accumulation in the membranes at all?

    12. KD of the NP in water/lipid as

      Isn't it lipid/water rather than water/lipid? I strongly suspect it is given that in the table Pt is given as 100% for all three "nanoparticles" and C60 has a very high oil/water (eg Kd toluene water ~7.

    13. Specifically, a buckminsterfullerene, a curved OH-terminated graphene quantum dot (GQD), and GQD functionalized with two cysteine groups (cys-GQD) were used.(40) This selection covers NPs of similar size but different shape and hydrophilicity

      So all of the intro (and title) is a general blurb about nanoparticles going through membranes, but these three examples are tiny hydrophobic objects.

    14. ller nanoparticles can instead cross the membrane by passive transport, that is, by displacing, sometimes irreversibly, the lipids or by diffusing in the hydrophobic region of the membrane and then on the other side

      This is an extraordinary assertion that is not backed up by references.

    15. For particles with the smallest dimension larger than the membrane thickness, approximately above 10–15 nm, the permeation is generally controlled by membrane deformation(23) and endocytosis.(24)

      This gives the impression that particles generally permeate. This is contradiction with earlier statements that correctly indicate that they don't.

    16. an effective barrier. Nonetheless,

      That apparent contradiction is missing a crucial point. What is the proportion of material getting "cytoplasmic access"? The Cell Penetrating Peptides field is a right mess. One thing is sure: most (maybe all) CPPs enter via endocytotic pathways and for any CPP only a tiny proportion reaches the cytosol. My own experience with the TAT-HA2 peptide was not particularly encouraging. Importantly, when "access to the cytosol" is measured by a biological outcome (e.g. transfection or toxicity), this can be achieved by a rare event. In other words, depending on the conditions, efficient transfection (e.g. 75% of cells transfected) can be achieved with very low percentage of particles reaching the cytosol (e.g. 99.9% in endosomes; 0.1% escape).

    17. ensing of cellular behavior.(6−10)

      Again, all of these papers are chemistry papers describing the synthesis of new materials which, according to their authors, could be useful for deep tissue imaging etc. Some of these are 5+ years old. These are indeed examples of "engineering for applications" but not of applications. Essentially no biologists use these materials for their imaging or sensing needs.

    18. led release,(3,5)
    19. such as drug delivery,(2−4)

      It enables engineering for applications... But it does not enable applications. None of these examples of drug delivery are remotely realistic. These are examples of chemistry papers not of drug delivery applications. The first paper (ref 2) is so far from drug delivery application that it does not even have cell culture experiments (not to mention preclinical or clinical work). Ref 3-4 are also mostly materials synthesis/characterization papers ; they do have some cell uptake/toxicity experiments. Still million miles away from "applications in drug delivery".

    20. are especially frustrating in biomedicine. Indeed, recently, there has been a blooming of applications

      Is it just me or is there a disconnect, even a contradiction between "especially frustrating" and "blooming of applications"?

    21. However, this is not the case for most macromolecules, such as proteins or nanoparticles (NPs), whose hydrophilicity and large size hamper direct diffusion through the membrane lipid bilayer.(1)

      Exactly. Nanoparticles large size and hydrophilicity hamper direct diffusion through the membrane bylayer. So far so good.

  6. Jun 2019
    1. As examples, the delivery of RNA with nanoparticles (in the product patisiran), has been approved by EMA/FDA in 2018,

      it is a liposome for delivery to the liver...

  7. May 2019
    1. “We didn’t know for decades that asbestos was dangerous,” says Michelle Lynch, a chemist and director of Enabled Future Limited, a London-based consultancy on chemicals and advanced materials. “We couldn’t prove that smoking was dangerous for decades. And the same [could] be true of nanotechnology.”

      First, we knew. Second, there was disinformation campaigns by powerful lobbies. Third, the analogy does not work because smoking or asbestos are two well-defined products whose dangerosity can be evaluated. The same cannot be said of "nanoparticles" - the question itself is ill posed. Maybe there is a lobby of the titanium dioxide in the food industry that try actively to prevent us from seeing the toxicity. If so, it must be aggressively investigated. What I see more is poor science and poor journalism that lump things together to create confusion and fear.

    2. Technological developments over the past two decades have meant that we can now engineer tiny particles much more easily – and their unusual properties make them useful in the food industry. They are currently used to change the texture, appearance and flavor of various foods. For example, silicon dioxide is added to salts, spices and icing sugar to improve their flow

      Again, this is deeply misleading. It gives the impression that there is something really new with all this nanotech engineering happening in the past two decades... and then talks about silicon dioxide which has been used for many more than two decades. I very much doubt that its formulation has changed much in the meantime. Here is a 1986 review "Food applications and the toxicological and nutritional implications of amorphous silicon dioxide." The difference: they use the word "colloid" (appears 19 times in the article) rather than "nanoparticle" (nowhere to be seen - but it is the same). https://www.ncbi.nlm.nih.gov/pubmed/3011357

    3. This suite of ingredients, engineered to almost atomic scale

      It is completely false and misleading to describe nanoparticle food additives as "engineered to almost atomic scale". These are crude polydisperse materials which for most have been in use for a long time, long before the word "nanoparticle" became fashionable.

    4. have unintended effects on cells and organs, particularly the digestive tract.

      That review is actually much much more balanced than what this sentence suggests. Notably it includes the fact that the human body has been exposed to nanoparticles for millions of years and has mechanisms to deal with it, and the fact that nanoparticles can be beneficial or toxc... in other words, the fact that they are nanoparticles does not tell us much about potential toxicity.

    5. There are also indications that nanoparticles might get into the bloodstream and accumulate elsewhere in the body. They have been linked to inflammation, liver and kidney damage and even heart and brain damage.

      These examples are listed to make a general point about "nanoparticles" but they bring together two different materials, various routes of exposure, etc and simplify everything. This is absurd as can be shown by the following thought experiment: imagine the same paragraph about "molecules" lumping together drinking benzene, water and too much alcohool. Surely you would have to conclude that the unintended effects of water are something to be very wary of.

    6. the technology

      What does this mean? Nanoparticles are certainly not a technology. Even Nanotechnology is not "a technology".

    7. Health effects from titanium dioxide observed in the lab were particularly acute in young animals, which is a concern given that children are especially exposed to it through candies, chewing gum and desserts.

      This sentence really shows the absurdity of the situation. The exposition of children to candies, chewing gums and desserts is an enormous and undisputed health problem, documented, leading to huge costs and suffering. Here however the panic is about the non-demonstration of an absence of risks.

    8. “There might be concerns for toddlers when you have a small body mass that you’re eating a lot of these candy products,” says Christine K Payne, associate professor of Mechanical Engineering and Materials Science, Duke University

      Again... there IS a concern if a small body eats lots of candy. There is absolutely no doubt of that. I suppose if fear of nanoparticles reduce ingestion of candies we might see a health benefit.

    9. Hendren. She says that asking if nanoparticles are harmful is like asking: “Is every single thing on the periodic table when taken down to a certain size safe or dangerous?”

      Well exactly: it is complete nonsense. So why exactly are we doing this?

    10. “It’s a new technology;

      It is not a new technology. First, what is "it"? Nanoparticles? Their use in food? If so, as noted above, we are talking at least half a century (for the examples in this article) or millenia depending exactly on the definition. Second, it is not "a technology".

    11. McClements pointed out that silver nanoparticles, widely used in packaging as antimicrobials to keep food fresh, can leach into foods and potentially kill off good bacteria in your gut. Scientists say this technology’s use in food packing has exploded over the past 15 years, but no one tracks all of its uses or knows what the exact combined exposure might be for the average consumer. “You can go to Walmart and you can buy little Ziplock sandwich bags that have nanoparticles in the plastic because you get improved shelf life because of reduced bacterial growth as the ions from the nanoparticles are slowly released,” says White. “These materials are out there and we are being exposed to them.”

      There is really no lack of research on silver toxicity.

    1. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function

      Really? "minute size" compared to what? What is the proportion that translocates? How does it compare to other potentially toxic agents such as dangerous small molecules?

  8. Apr 2018
    1. The functionality of the SmartFlare protocol has been demonstrated in literature several times [15, 23, 31, 32].

      Not sure what is meant by this sentence, but none of those references have anything to do with smartflares.

    2. As those SmartFlare probes were designed for RNA targeting while using the gold core just as a carrier for the dye, successful SmartFlare binding to the Her2 gene product in the endoplasmic reticulum would mean a GNP concentration in the ER around the cell nucleus. Thus, in tumor types where certain genes are considerably upregulated, the RNA of such genes could be targeted so that the GNPs accumulate in the tumor cells only, leading to an increased radio-sensitivity compared to non-tumor cells without extra-ordinary up-regulation

      See above. This is a considerable misunderstanding of the Smartflare technology: the gold is not supposed to stay where the mRNA was. In fact, to address this 'problem', Mirkin (the inventor of the SmartFlare) even developed another version where the mRNA stay bound to the mRNA (the famous stickyflare).

    3. RNA targeting nanogold probes that are aiming for the Her2 gene product in the endoplasmic reticulum (ER)

      The SmartFlares are supposed to enable the measurement of mRNA levels in cells. Nobody has ever claimed that they can target mRNA, even less so target specific cells on the basis of their mRNA levels. There is no reason to believe that the amount of gold in different cells should correlate with the amount of mRNA. In fact the working principle of the sensor assumes that all cells uptake the same amount of SmartFlare but the fluorescence levels are different depending on the amount of mRNA because of the release of a reporter strand from the nanoparticle. [the technology does not work, but that is another story]

    4. while GNPs smaller than 100 nm in diameter can enter the tumor tissue [12]

      Reference 12 does not show this at all. There are no in vivo experiments nor any experiments with tissues (as the title indicates).

    5. GNPs smaller than 30 nm are leaving the cell again by passive diffusion [3, 14, 15]

      Reference 3 does not include any study of passive diffusion through membranes. To the contrary, it includes a liposomal transfection agent to help oligonucleotide-capped nanoparticles go inside cells. Reference 14 does not mention passive diffusion whatsoever. It is an article about active transport (endocytosis and exocytosis). Reference 15 includes the sentence "GNPs smaller than 30 nm are leaving the cell again by passive diffusion (15)" (that's right, identical word for word)... where (15) is reference 14 above.