An Escape Composition
Custodio Groves
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Polymer nanoparticles offer significant benefits for improving delivery of biological therapeutics such as DNA and proteins, as they allow the cargo to be protected until it is delivered to a target cell. However, there are still challenges with achieving efficient delivery to the optimal cellular region. One significant roadblock is escape of nanoparticles from within the endosomal/lysosomal compartments into the cytosol. Here, we review the recent advances in understanding endosomal escape of polymer nanoparticles. We also discuss the current progress on investigating how nanoparticle structure can control endosomal escape. It is important to understand the fundamental biological processes that govern endosomal escape in order to design more effective therapeutic delivery systems.
Abstract. We refine a recently presented method to estimate ion escape from non-magnetized planets and apply it to Mars. The method combines in-situ observations and a hybrid plasma model (ions as particles, electrons as a fluid). We use measurements from the Mars Atmosphere and Volatile Evolution (MAVEN) mission and Mars Express (MEX) for one orbit on 2015-03-01. Observed upstream solar wind conditions are used as input to the model. We then vary the total ionospheric ion upflux until the solution fits the observed bow shock location. This solution is a self-consistent approximation of the global Mars-solar wind interaction at this moment, for the given upstream conditions. We can then study global properties, such as the heavy ion escape rate. Here we investigate the effects on escape estimates of assumed ionospheric ion composition, solar wind alpha particle concentration and temperature, solar wind velocity aberration, and solar wind electron temperature. We also study the amount of escape in the ion plume and in the tail of the planet. Here we find that estimates of total heavy ion escape are not very sensitive to the composition of the heavy ions, or the amount and temperature of the solar wind alpha particles. We also find that velocity aberration has a minor influence on escape, but that it is sensitive to the solar wind electron temperature. The plume escape is found to contribute 29 % of the total heavy ion escape, in agreement with observations. Heavier ions have a larger fraction of escape in the plume compared to the tail. We also find that the escape estimates scales inversely with the square root of the atomic mass of the escaping ion specie.
This is a very interesting paper in order to have a better understanding of the roles of different parameters on ion escape at Mars, e.g., ion composition, alpha particle concentration, temperature, solar wind velocity aberration, and solar wind electron temperature. I think it is an important contribution for which, I would like to suggest some minor comments to be considered.
> We thank the reviewer for insightful and constructive comments that we think will improve the paper. Please find our replies below to some of the issues brought up. The content of these replies would be incorporated in a revised version of the paper.
> We agree that the reference and description was not clear. The discussion about the composition we selected is in section 3.1.2, along with the justification for the selected composition. After examining the escape for different compositions, we conclude at the end of 3.1.2 that the escape is not very sensitive to the exact composition. Since some observations indicate more O+ and some more O2+, we selected equal O+ and O2+ densities at the exobase, with also 10% of CO2+.
Also in Section 2.2, it would be good to explain a bit more the different Upflux scenarios of Table 2, which are very briefly mentioned, but a reader may not understand why these 3 scenarios are done, why are they important or actually their main differences.
> This is an optimization process to find a simulation run that best match observations. We select different upflux values and perform simulations until we find a good fit to the bow shock location. By "good fit" we mean that the difference between a simulation and the observed bow shock along the spacecraft trajectory is on the order of the simulation cell size. This can require many model runs. In the paper we present the best fit (Upflux 2) along with the two bracketing runs that give a bow shock location that is too far or too close to the planet (Upflux 1 and 3).
> Actually it is not important if the extent of the simulation domain along each axis is symmetric or not, as long as the simulation domain is large enough to contain all of the interaction region. So the simulation domain is selected to contain the bow shock.
> The Mars model has a sphere centered at the origin with a radius of 3380 km, representing the solid planet. We have a spherical obstacle with a radius of 3550 km (the inner boundary of the simulation), representing the exobase at the altitude of 170 km. All ions inside the obstacle are removed from the simulation. The resistivity is 7e5 Ωm in the solid planet. Outside the planet the resistivity is 5e4 Ωm, in the ionosphere and the surrounding plasma.
I believe a discussion section is needed. As any model, several upgrades are still needed to incorporate, such as the role of crustal fields at Mars or the neutral corona. Some discussion about these two aspects should appear in the paper with relation to what we know from empirical experience and other models, and how this model compares to others. In addition, it would be good to discuss how the numbers/results provided in this work would compare with other observations at different solar activity levels, seasons, etc. Future work may be needed to get a comprehensive picture, but based on the literature, I believe it is necessary to understand how this model may potentially compared under different circumstances, or what to expect from the model.
> We should discuss more about crustal fields in the paper. The bow shock location has been found to depend on the location of the magnetic anomalies relative to the solar wind flow (Fang et al., 2017; Garnier et al., 2022). It is unclear if this is because the fields expand the bow shock or because the presence of the fields increase the ion escape. The latter may not require crustal fields in the model used in our algorithm, as the parameter that we vary is the amount of ions near Mars available to escape. If the crustal fields in a specific geometry enhance escape, this will be captured in the algorithm because the best fit bow shock will be further out and require larger upflow at the inner boundary. In contrast, if the crustal fields in a specific geometry depress escape, the bow shock will be closer to the planet. An investigation of the effect of crustal fields on escape using our methodology is a topic for future studies.
> We have submitted a follow-up paper to JGR, about how solar activity and upstream solar wind conditions affect the ion escape using our method. So in this paper we do not discuss that, instead focusing on some basic parameters that have been rarely investigated before.
Data: MAVEN key parameters are used. However, there are tons of them! It would be much appreciated a proper description of the parameters used and from which instrument they come from, if they have any caveats, etc. In addition, in line 179, the 4117 orbits examined, are also key parameters? Please describe it.
> It includes solar wind density, solar wind velocity, and solar wind proton temperature from SWIA; solar wind electron temperature from the Solar Wind Electron Analyzer (SWEA); and IMF from the Magnetometer (MAG).
> This was not clearly explained. Figure 7 actually shows the uncertainties, but not with error bars. The observed solar wind electron temperature varies in the solar wind in the range given by the x-axis. This results in the variation in escape are shown on the y-axis. So the uncertainty in electron temperature gives an escape in the range 6.5-7.0e24. This is the uncertainty in escape caused by the electron temperature uncertainty.
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