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公益良知生物学家深度解析注射脂质纳米颗粒 记者综述

Public Interest Biologist’s In-Depth Analysis of Lipid Nanoparticle Injections Journalist’s Overview

Overview: Investigative journalists have discovered that each year, the highest university admission scores in China are for the biomedical sciences department. The dictatorial CCP seeks to exploit the most intelligent individuals to research biomedicine, with the aim of conducting inhumane and destructive research. Once these young scholars publish their “scientific” results, they often meet with mysterious deaths… In 2021, an alarming discovery was made when tracing the Chinese Academy of Sciences’ biological patent literature: “The research has been done! Now we need to figure out how to put it into the human body…” When journalists exposed these dark secrets, their website accounts were banned or silenced under various pretexts. / France: Freedom, Health, and Human Rights Journalist: Han Rongli

Image Caption:
The Pfizer💉 R&D center building in Wuhan is only 10–15 kilometers away from the Wuhan Institute of Virology.
China’s PCR tests are like rebellious children, aiming to implant nano-biological particles. Their real purpose is not for extraction and testing, so! No need for saliva tests outside the body.

⸻

This translation conveys the original text with an emphasis on the sinister implications of the research, as well as the suppression of journalists and the alleged connections between various locations and entities.

综述：调查记者发现，每年中国高考最高录取分数线是生物医药系，独裁中共要攫取最聪明人研究生物医药、目的是进行反人类破坏研究，而这些年轻学子一旦研究发表出“科技”成果、就会被诡异死亡。…2021年，追溯中国科学院生物专利文献惊悚发现“东西是研究出来了！接下来要看如何放入人体…”，当记者披露这些黑暗时，网站账号被以各种理由封闭禁言。/ 法国：自由健康人权记者：韩荣利

综合图片说明：
中国武汉辉瑞💉研发中心大厦距离武汉病毒🦠研究所距离仅10～15公里。
中国产PCR比逆子，目的是植入纳米生物颗粒，其真实目的不是取出检验🧪，所以！不用唾液体外测试。

Why Lipid
Nanoparticles are
Colloidal Multi-
Particle Systems (English Transcript of my new Youtube Presentation)
And why traditional ADME models, based on mass assumptions and total dose, will fail
GENERVTER BÜRGER
8 JAN 2026 AT 14:10

https://open.substack.com/pub/genervter/p/why-lipid-nanoparticles-are-colloidal

…Interestingly, more recent studies show that endosomal escape preferentially occurs in the early endosome and is strongly time-dependent, suggesting that it is not the maximally acidic environment of late endosomes or lysosomes that is decisive, but rather a narrowly defined time and pH window. This explains why modRNA release is so inefficient. Current studies estimate that only about 3–15 percent of modRNA is translated into protein at all. These uptake and release processes disrupt overall cellular homeostasis—that is, the cell’s internal balance. In particular, endosomal disruption triggers highly inflammatory processes.

Disruptions in communication within a single cell can lead to systemic effects in neighboring and even distant cells, for example through the release of hormones, growth factors, pro-inflammatory cytokines, and numerous other extracellular signaling pathways. In addition, it is reasonable to assume that the process of transfection and endosomal escape places a heavy burden on the cell’s energy budget, making it plausible that the transfected cell may enter senescent states—that is, switch to minimal operation and focus solely on self-preservation. This may, for example, be promoted by increased secretion of interleukin-6, which has been demonstrated multiple times in vivo.
Additionally, another possible and already partially documented phenomenon is the epigenetic reprogramming of monocytes, resulting in reduced immune surveillance. This means that their overall functionality is fundamentally altered by specific processes.

Furthermore, as repeatedly confirmed in vivo, there is overexpression of specific monocyte ligands, namely programmed death ligand-1 (PD-L1), which further favors the scenario described here. Epithelial cells can become stressed and senescent, thereby influencing neighboring cells, while those neighboring cells may nevertheless remain proliferative. This means they can continue to divide despite being in a stressed environment, which increases the likelihood of malignant transformation.

Under such conditions, control of transformed cells is severely impaired—a scenario that could systemically promote the development of metastases, as both immune surveillance and cellular homeostasis are profoundly disrupted.

In an extensive mouse experiment by Qin et al., it was shown that even mere exposure—that is, contact with empty LNPs as currently used—led to markedly altered immune responses to viral and bacterial pathogens in the mice. Furthermore, the experiment demonstrated that this effect was transmitted to the next mouse generation, as would be expected if profound epigenetic changes were involved.
…

Biodegradation
Biodegradation describes the breakdown of a drug’s molecules and their intermediate products until complete termination—that is, how a product is degraded and how many phases are involved.
There is not much to say about the biodegradation of the individual lipids, not because there is little to say, but because these processes are poorly understood. Very few studies have been conducted, and current knowledge of the precise degradation pathways remains largely speculative.
It is clear that certain enzymes—so-called -ases—must cleave the fatty acid tails of the lipids. However, particularly with ionizable lipids, there are acute problems, and these processes are more than inadequately characterized. It is known that the ionizable head groups, especially tertiary amines, are difficult or impossible to degrade, since esterases—i.e., ester-based enzymes—tend, particularly in the case of ALC-0315, to compete with oxidation processes due to its structure, resulting in prolonged bioactive persistence.
Furthermore, it appears biologically plausible that DSPCs—that is, the synthetic phospholipids of LNPs—may, even after degradation, be recycled and reintegrated into the cell membrane, thereby altering the overall membrane structure. In other words: we know almost nothing about the long-term consequences.
I hope that up to this point I have been able to make clear and comprehensible just how complex, unpredictable, and fraught with unanswered questions lipid nanoparticles are, and how they function in principle. And I hope it has become clear why—driven solely by the PCR-test pandemic and regulatory negligence—such an insufficiently researched technology, with potentially severe long-term consequences that we cannot yet estimate in magnitude or probability, was deployed at mass scale in humans. The largest human in vivo experiment in the history of modern medicine was initiated.
If you have been able to follow up to this point and understand at least the essentials, then you will understand why the greatest error lay—and still lies—in treating modRNA and LNPs as separate entities, and why traditional pharmacological notions of a simple “mass × total molecule number equals toxic effect” model fail to apply.
If you wish to understand the details more deeply, I recommend reading both the work by myself, Maria Gutschi, and Dr. Seneff, as well as the paper by Maria and myself that was shown at the beginning of this lecture, where we extensively review all mechanisms and properties discussed here using the current LNP literature.

單個細胞內通訊中斷可能導致鄰近甚至遠處細胞的系統效應，例如透過釋放激素、生長因子、促炎細胞因子和許多其他細胞外訊號通路。 此外，可以合理地假設，轉染和內切體逃逸過程給細胞的能量預算帶來了沉重的負擔，這使得轉染細胞可能進入衰老狀態——也就是說，切換到最小操作，只專注於自我保護。 例如，白細胞介素-6的分泌增加可能會促進這一點，這在體內已經多次證明。

此外，另一個可能且已經部分記錄的現象是單核細胞的表觀遺傳重新寫程式，導致免疫監測降低。 這意味著它們的整體功能從根本上被特定過程所改變。

目前部署的modRNA-LNP平臺中使用的可電離脂質是三級胺。 這些三級胺——特別是ALC-0315和SM-102——的酸解離常數（pKa）約為6.2至6.8。 因此，在中性環境中，它們主要是無電荷的，因為整體顆粒——脂質奈米顆粒本身——在生理pH值下幾乎是電中性的。 此外，聚乙二醇化脂質旨在防止過早的電荷變化。 pH值代表質子濃度的負十次對數，因此與酸鹼反應直接相關。 簡單來說，pH值決定了質子吸收的速度和程度。

此外，正如體內反覆證實的那樣，特定單核細胞配體的過度表達，即程式性死亡配體-1（PD-L1），這進一步有利於此處描述的情況。 上皮細胞可能會受到壓力和衰老，從而影響鄰近的細胞，而那些鄰近的細胞可能仍然會增殖。 這意味著，儘管它們處於緊張的環境中，但它們可以繼續分裂，這增加了惡性轉化的可能性。

當pH值低於pKa時，這些可電離的脂質被質子化。 這種情況只發生在內染色體隔間內，pH值在成熟過程中下降到大約4.5-5.0，至少根據經典假設和早期的觀察。 在這些條件下，來自酸性環境的質子與可電離脂質結合，導致脂質奈米顆粒的重組。 脂質pKa和區域性pH值之間的關係對隨後的細胞內過程具有決定性意義。

有趣的是，最近的研究表明，內染色體逃逸優先發生在早期內切體中，並且與時間有很強的依賴性，這表明決定性的不是晚期內切體或溶酶體的最大酸性環境，而是狹義的時間和pH值視窗。 這解釋了為什麼modRNA的釋放效率如此低。 目前的研究估計，只有大約3-15%的modRNA被翻譯成蛋白質。 這些吸收和釋放過程破壞了整體細胞的穩態——即細胞的內部平衡。 特別是，內染色體破壞會引發高度炎症的過程。

在這種情況下，轉化細胞的控制受到嚴重損害——這種情況可能會系統地促進轉移的發展，因為免疫監測和細胞穩態都受到嚴重破壞。

在Qin等人的一項廣泛的小鼠實驗中，表明，即使只是接觸——即與目前使用的空LNPs接觸——也會導致小鼠對病毒和細菌病原體的免疫反應明顯改變。 此外，實驗表明，如果涉及深刻的表觀遺傳學變化，這種效應會傳遞給下一代小鼠。

生物降解
生物降解描述了药物分子及其中间产物的分解直至完全终止，即产物如何降解以及涉及多少个阶段。
关于单个脂质的生物降解，没有太多可说的，不是因为没什么可说的，而是因为人们对这些过程知之甚少。 进行的研究非常少，目前对精确降解途径的了解在很大程度上仍然是推测性的。
很明显，某些酶（所谓的酶）必须切割脂质的脂肪酸尾部。 然而，特别是对于可电离的脂质，存在严重的问题，并且这些过程的特征还不够充分。 众所周知，可电离的头基，尤其是叔胺，很难或不可能降解，因为酯酶（即基于酯的酶）由于其结构而倾向于与氧化过程竞争，导致生物活性持久性延长，尤其是在 ALC-0315 的情况下。
此外，从生物学角度来看，DSPC（即 LNP 的合成磷脂）即使在降解后也可能被回收并重新整合到细胞膜中，从而改变整体膜结构。 换句话说：我们对其长期后果几乎一无所知。
我希望到目前为止，我已经能够清楚和理解脂质纳米颗粒的复杂性、不可预测性和充满悬而未决的问题，以及它们的原理如何发挥作用。 我希望人们已经清楚为什么——仅由 PCR 检测大流行和监管疏忽驱动——这种研究不足、可能带来严重的长期后果（我们尚无法估计严重程度或概率）的技术被大规模应用于人类。 现代医学史上最大规模的人体实验开始了。
如果您能够跟进这一点并至少理解要点，那么您就会明白为什么最大的错误在于（并且仍然存在）将 modRNA 和 LNP 作为单独的实体来对待，以及为什么简单的“质量 × 总分子数等于毒性效应”模型的传统药理学概念无法适用。
如果您想更深入地了解细节，我建议您阅读我自己、Maria Gutschi 和 Seneff 博士的工作，以及本讲座开头展示的 Maria 和我自己的论文，其中我们使用当前的 LNP 文献广泛回顾了此处讨论的所有机制和特性。

You can't sell turkey tail mushrooms, a 2000 year old adaptogenic superfood because it's “novel”, and yet these clowns were able to inject an agent in billions of arms without knowing how it works.

“… They are only metastable and bind seemingly randomly to endogenous proteins almost immediately. As of the time of this lecture, this process is still not sufficiently understood.”

“… There is not much to say about the biodegradation of the individual lipids, not because there is little to say, but because these processes are poorly understood. Very few studies have been conducted, and current knowledge of the precise degradation pathways remains largely speculative.”

“… Furthermore, it appears biologically plausible that DSPCs—that is, the synthetic phospholipids of LNPs—may, even after degradation, be recycled and reintegrated into the cell membrane, thereby altering the overall membrane structure. In other words: we know almost nothing about the long-term consequences.” 你不能出售火鸡尾蘑菇，这是一种已有 2000 年历史的适应性超级食品，因为它很“新颖”，但这些小丑却能够在不知道其工作原理的情况下将一种药剂注射到数十亿只手臂中。

“……它们只是亚稳态的，并且几乎立即与内源性蛋白质看似随机地结合。截至本讲座时，这个过程仍然没有得到充分的了解。”

“……关于单个脂质的生物降解，没有太多可说的，不是因为没有什么可说的，而是因为人们对这些过程知之甚少。进行的研究很少，目前对精确降解途径的了解在很大程度上仍然是推测性的。”

“......此外，从生物学角度来看，DSPC（即 LNP 的合成磷脂）即使在降解后也可能被回收并重新整合到细胞膜中，从而改变整体膜结构。换句话说：我们对其长期后果几乎一无所知。”

https://substack.com/@doorlesscarp/note/c-197791204

At this point, as a response to the hopefully constructive discussion with Dr. Kremer, I would like to clarify a few things and deliver a rather dry technical lecture that may finally resolve some misunderstandings and show why Dr. Kremer and I were in fact talking about two completely different things.
Regarding the effects of modRNA, we—the authors (me, Maria Gutschi and Dr. Stephanie Seneff) of the papers shown here—see it similarly to most critical scientists: it already has considerable disruptive potential. However, we argue against the oversimplified assumption that modRNA itself is the root of all evil.

Quite the opposite: when we speak of LNP-modRNA injections, we can only speak of LNP-modRNA. The translated spike protein merely acts as an additional accelerant on top of this, amplifying various pathogen-like mechanisms.
In short, we are dealing with very complex, dynamic colloidal particle systems.
But what exactly are self-assembling, colloidal, and above all dynamic particle systems?

在這一點上，作為對希望與博士進行建設性討論的回應。 Kremer，我想澄清一些事情，並發表一個相當枯燥的技術講座，最終可能會解決一些誤解，並說明為什麼博士 事實上，Kremer和我談論的是兩件完全不同的事情。

關於modRNA的影響，我們——作者（我、Maria Gutschi和Dr. Stephanie Seneff）這裡顯示的論文——與大多數批判性科學家相似：它已經具有相當大的顛覆性潛力。 然而，我們反對過度簡化的假設，即modRNA本身就是萬惡之源。

恰恰相反：當我們談論LNP-modRNA注射時，我們只能談論LNP-modRNA。 翻譯後的尖峰蛋白只是在此之上充當額外的加速劑，放大各種類似病原體的機制。

簡而言之，我們正在處理非常複雜、動態的膠體粒子系統。

但究竟什麼是自組裝、膠體，最重要的是動態粒子系統？

A colloidal particle system describes an assembly composed of multiple individual components in which the individual physicochemical properties of the constituent particles (including the modRNA) mutually influence one another. Their mixing ratios determine the macroscopic behavior of the overall formulation in the initial medium, without allowing for a simple derivation of system properties from the properties of the individual particles, or vice versa—especially when the medium changes.
A central criterion of colloidal systems is their ability to undergo phase transitions. This condition is fulfilled by lipid nanoparticles: after cellular uptake, they undergo a pH-driven phase transition in which protonatable lipids change their charge and packing properties and transition from a structurally stable particle phase into a membrane-destabilizing, fusogenic phase. They are therefore dynamic, colloidal assemblies.
Let us now calmly revisit the slide that Maria Gutschi and I developed to better conceptualize the self-organizing principle of lipids in relation to the overall lipid nanoparticle.
In panel A, the schematic of a single lipid nanoparticle is shown. Four lipids form the outer layer and the interior of the lipid nanoparticle, depicted in different colors. Inside, individual rings are formed. The individual lipids bind and, through their differing physicochemical properties, form the overall particle containing the encapsulated modRNA. From this alone—and because physical interactions and forces are interacting here—it necessarily follows that a strongly negatively charged RNA must exert an influence on this particle. The modRNA is a so-called polyanionic polymer. Through its negative charge, it inevitably generates mechanical tension and thus an intrinsic organization of the lipid nanoparticle.
The formulations of the C-19 LNP-modRNA injections consist of an ionizable lipid containing a tertiary amine, the synthetic phospholipid DSPC, a PEGylated lipid, and cholesterol, which primarily resides in the inner interstitial spaces.
These four lipids, in specific stoichiometric ratios, form the complete particle. A single lipid nanoparticle contains between 30,000 and 60,000 ionizable lipid molecules. As demonstrated in countless publications, each of these lipids is in constant motion and behaves depending on the relative ratios of the lipid components to one another and on the encapsulated modRNA. It should therefore already be evident at this point that a simple mass-based model cannot be sufficient.
Traditional pharmacokinetics, however, relies on mass and particle number in its ADME framework (absorption, distribution, metabolism, and excretion), assuming stable molecules that do not undergo structural changes when fundamental conditions change—that is, molecules that do not undergo phase transitions.
In Figure B, you can see what happens when an LNP transitions from a medium of pure alcohol, such as ethanol, into plasma or serum. Within minutes to at most one hour, dozens of endogenous proteins bind around the LNP, because it still emits a very slight outward charge. I will address uptake and distribution pathways, as well as this so-called protein corona, in more detail later.
This means that there is always a minimal scaffold on which further processes build. It is not the case that everything disintegrates completely and is then reassembled from scratch. For example, Liu et al., and in particular Liau et al., demonstrated using scanning electrochemical microscopy that the PEGylated lipid detaches first, followed by the ionizable lipid, and finally DSPC, leaving only cholesterol and the modRNA behind. In addition, cholesterol exchange occurs during LNP uptake. More on this later.
In summary, nanoparticles do not permit traditional drug analysis because they restructure themselves upon changes in the surrounding medium. However, applying a traditional pharmacological model based on mass requires that the original structural ratios remain constant.
After having examined the fundamental physicochemical properties of lipid nanoparticles as used by Pfizer and Moderna in the COVID-19 injections, the distinction between lipid nanoparticles and conventional liposomes must now be briefly clarified.
In one of his recent discussions with Dr. Wodarg, Dr. Kremer claimed that liposomes or even micelles can be equated with lipid nanoparticles (LNPs). This equivalence, however, is not tenable. Even though I already addressed this during the discussion, I would like to explicitly reiterate it here.
…

Figure is actualized and not original from V1 of Maria and my preprint (we will add a v2 if we find free minute)
What actually happens after injection? The devil is in the details.
On this slide, Maria and I reconstructed the in vivo “journey” of LNPs in our first paper.
LNPs have multiple uptake pathways through which they can reach various organs via different mechanisms. While the route is influenced by the mode of administration—i.e., whether injected intravenously or intramuscularly—it is not fully determined by it. Once LNPs enter the organism, their physicochemical properties are too randomized to allow precise prediction of their exact trajectory. As shown earlier in the structural slide, Figure B, a wide variety of endogenous proteins bind to LNPs as soon as they enter the system and undergo their first medium transition. This leads to the formation of the so-called protein corona. The formation of the protein corona occurs via different mechanisms that are not yet fully understood. However, it can be assumed that already at this stage—with billions of lipid nanoparticles containing trillions of individual lipids—the first biological effects on proteostasis may arise, meaning initial disturbances in protein homeostasis are possible.
Let us now briefly trace the cellular uptake pathways to better understand the journey of an LNP. First, we consider what must happen at all for a cell to release modRNA, without yet going into the precise release mechanisms—I will return to those later.
After injection, several research groups made remarkable observations: a fraction of the LNPs enters the bloodstream directly via diffusion, meaning slow percolation through muscle tissue. The majority of LNPs initially remains in the muscle, where they attract immune cells, in particular migrating T cells and, above all, dendritic cells.
In addition, a smaller fraction can reach muscle-resident macrophages and be taken up via alternative uptake pathways, although this occurs rarely and nonspecifically. In this context, transfection refers to an uptake process that is not comparable to the originally intended uptake mechanisms. In this presentation, we focus primarily on dendritic cells, as these are described in the literature as the immune cell type most frequently transfected by LNPs. Dendritic cells are professional antigen-presenting cells and migrate to lymph nodes after encountering a pathogen.

Evidence has established a potential relationship between protein recruitment to the LNP surface and organ targeting14,24,25,26 and functionality1,28, necessitating further characterization of the interactions between proteins and LNPs. As such, we seek to explore how the LNP identity is redefined by the spontaneous adsorption of biofluid proteins, and how these LNP corona proteins impact their function. Upon injection, nanoparticles encounter various biological tissues and compartments. Biomolecules such as proteins spontaneously interact with the nanoparticles and form an associated protein corona29,30,31,32. Proteins with a strong affinity for the particle surface form a "hard corona"" while more loosely associated proteins form a dynamic "soft corona"30. These corona proteins modify nanoparticle function and localization in vivo, as this outer protein layer changes how nanoparticles interact with cell-surface receptors, impacting biodistribution 33.34 and cell-specific uptake35.36. Upon systemic injection, most nanoparticles are cleared by the liver and, in particular for LNPs, adsorption of apolipoprotein E (ApoE) facilitates interactions with low-density lipoprotein receptors on the surface of hepatocytes
https://www.nature.com/articles/s41467-025-63726-2

證據已經確立了對LNP表面的蛋白質招募與器官靶向14,24,25,26和功能1,28之間的潛在關係，這需要進一步表徵蛋白質和LNP之間的相互作用。 因此，我們試圖探索如何透過生物流體蛋白的自發吸附來重新定義LNP身份，以及這些LNP日冕蛋白如何影響其功能。 注射後，奈米顆粒會遇到各種生物組織和隔間。 蛋白質等生物分子自發地與奈米顆粒相互作用，形成相關的蛋白質電暈29,30,31,32。 對粒子表面有強烈親和力的蛋白質形成「硬日冕」，而更鬆散相關的蛋白質形成動態的「軟日冕」30。 這些電暈蛋白在體內改變奈米顆粒的功能和定位，因為這種外層蛋白質改變了奈米顆粒與細胞表面受體相互作用的方式，影響生物分佈33.34和細胞特異性攝取35.36。 全身注射後，大多數奈米顆粒被肝臟清除，特別是對於LNP，脂蛋白E（ApoE）的吸附促進了與肝細胞表面低密度脂蛋白受體的相互作用

網址：https://www.nature.com/articles/s41467-025-63726-2

胶体颗粒系统描述了由多个单独组分组成的集合体，其中组成颗粒（包括 modRNA）的单独物理化学性质相互影响。 它们的混合比例决定了初始介质中整体配方的宏观行为，不允许从单个颗粒的属性简单推导系统属性，反之亦然——尤其是当介质发生变化时。
胶体系统的一个中心标准是它们经历相变的能力。 脂质纳米颗粒满足了这一条件：细胞摄取后，它们经历 pH 驱动的相变，其中可质子化脂质改变其电荷和堆积特性，并从结构稳定的颗粒相转变为膜不稳定的融合相。 因此，它们是动态的胶体组件。
现在让我们冷静地回顾一下 Maria Gutschi 和我开发的幻灯片，以更好地概念化与整个脂质纳米颗粒相关的脂质自组织原理。
A 图中显示了单个脂质纳米颗粒的示意图。 四种脂质形成脂质纳米颗粒的外层和内部，以不同的颜色表示。 内部形成单独的环。 各个脂质结合并通过其不同的物理化学特性形成含有封装的 modRNA 的整体颗粒。 仅凭这一点——并且因为物理相互作用和力在这里相互作用——必然得出带强负电荷的 RNA 必须对该粒子产生影响。 modRNA是所谓的聚阴离子聚合物。 通过其负电荷，它不可避免地产生机械张力，从而形成脂质纳米颗粒的内在组织。
C-19 LNP-modRNA 注射剂的配方由含有叔胺的可电离脂质、合成磷脂 DSPC、聚乙二醇化脂质和胆固醇组成，主要存在于内部间隙空间中。
这四种脂质以特定的化学计量比形成完整的颗粒。 单个脂质纳米颗粒含有 30,000 至 60,000 个可电离脂质分子。 正如无数出版物所证明的那样，这些脂质中的每一种都处于持续运动状态，其行为取决于脂质成分之间的相对比例以及封装的 modRNA。 因此，在这一点上应该已经很明显，简单的基于质量的模型是不够的。
然而，传统的药代动力学依赖于 ADME 框架（吸收、分布、代谢和排泄）中的质量和颗粒数，假设稳定的分子在基本条件发生变化时不会发生结构变化，即不发生相变的分子。
在图 B 中，您可以看到当 LNP 从纯酒精介质（例如乙醇）转变为血浆或血清时会发生什么。 在几分钟到最多一小时内，数十种内源性蛋白质就会结合在 LNP 周围，因为它仍然向外发射非常轻微的电荷。 稍后我将更详细地讨论摄取和分布途径，以及所谓的蛋白质电晕。
这意味着始终存在一个最小的支架，可以在其上构建进一步的流程。 并不是一切都完全解体，然后从头开始重新组装。 例如，Liu等人，特别是Liau等人，使用扫描电化学显微镜证明，聚乙二醇化脂质首先分离，然后是可电离的脂质，最后是DSPC，仅留下胆固醇和modRNA。 此外，胆固醇交换发生在 LNP 摄取过程中。 稍后会详细介绍这一点。
总之，纳米颗粒不允许进行传统的药物分析，因为它们会根据周围介质的变化自行重组。 然而，应用基于质量的传统药理学模型要求原始结构比例保持恒定。
在检查了辉瑞和 Moderna 在 COVID-19 注射剂中使用的脂质纳米颗粒的基本理化特性后，现在必须简要澄清脂质纳米颗粒和传统脂质体之间的区别。
在最近与 Wodarg 博士的一次讨论中，Kremer 博士声称脂质体甚至胶束可以等同于脂质纳米颗粒 (LNP)。 然而，这种等价是站不住脚的。 尽管我已经在讨论中提到过这一点，但我想在这里明确重申。

數字是實現的，不是來自Maria和我的預印本的V1的原件（如果我們找到空閒時間，我們將新增一個v2）

注射後到底發生了什麼？ 魔鬼在細節中。

在這張幻燈片上，Maria和我重建了第一篇論文中LNP的體內「旅程」。

LNP有多種吸收途徑，它們可以透過不同的機制到達各種器官。 雖然路線受到給藥方式的影響——即是靜脈注射還是肌肉注射——但它並不完全由它決定。 一旦LNP進入生物體，它們的物理化學特性過於隨機，無法準確預測其確切軌跡。 如圖B的結構幻燈片所示，各種內源性蛋白質一旦進入系統並經歷第一次介質過渡，就會與LNP結合。 這導致了所謂的蛋白質電暈的形成。 蛋白質電暈的形成是透過尚未完全瞭解的不同機制發生的。 然而，可以假設，在這個階段——數十億個脂質奈米顆粒含有數萬億個單獨的脂質——可能會對蛋白質穩定產生第一個生物影響，這意味著蛋白質穩態的初始干擾是可能的。

現在讓我們簡要追蹤細胞吸收途徑，以更好地瞭解LNP的旅程。 首先，我們考慮細胞釋放modRNA必須發生什麼，而還沒有進入精確的釋放機制——我稍後會回到這些。

注射後，幾個研究小組做出了顯著的觀察：一小部分LNP透過擴散直接進入血液，這意味著透過肌肉組織緩慢滲透。 大多數LNP最初留在肌肉中，在那裡它們會吸引免疫細胞，特別是遷移的T細胞，最重要的是樹突狀細胞。

此外，較小的部分可以到達肌肉駐留的巨噬細胞，並透過替代的攝取途徑被吸收，儘管這種情況很少發生，而且非特異性。 在這種情況下，轉染是指與原定的吸收機制無法比擬的吸收過程。 在本簡報中，我們主要關注樹突狀細胞，因為這些細胞在文獻中被描述為最常被LNP轉染的免疫細胞型別。 樹突狀細胞是專業的抗原呈現細胞，在遇到病原體後會遷移到淋巴結。