1. Introduction
Cell structure and function are controlled by a complex regulatory networking process, in which molecular adaptation and interaction are essential to maintain cellular homeostasis following dynamic multi-omics rules and multi-systematic changes. This complex chemical process is an important mechanism for stabilizing the cell microenvironment. Abnormal cell structures and functions do not necessarily result from intrinsic alterations of intracellular molecules or substructures, but may also stem from extrinsic perturbations of molecular interactions, signal transduction pathways, and metabolic processes due to the imbalanced homeostasis of the intracellular chemical field. While abnormal cellular metabolism is the root cause of most diseases, changes in the intracellular chemical field may be the first phenotypic feature of the altered cellular metabolism. This imbalance may further aggravate the abnormal cellular structure and function, forming a vicious cycle. Here, we aimed to elucidate characteristics of the intracellular chemical field and its relationship with the intracellular microenvironment and homeostasis, as well as the occurrence and prognosis of diseases. We also proposed a new concept of the cellular chemical field and its constituent elements to aid understanding of the complex chemical process within the cells. We further elaborated on how the cellular chemical field affects cell function and metabolism, and expounded on its roles in disease diagnosis and treatment.
2. Concept of chemical field
In system biomedicine, characterizing the microstructure and its spatial distribution at subcellular and molecular levels, analyzing the relationships between these structures, and revealing the dynamic spatiotemporal changes in their interactions present an urgent challenge [
1]. These form the scientific basis for deciphering the disease mechanism and developing new drugs. By addressing these challenges, we can reveal the interaction network rules and functional phenotypes of multi-omics, for example, the genome, epigenetics, transcriptome, and proteome, to achieve a zero-toone breakthrough in basic science, clinical medicine, and pharmacy. Although the occurrence and development of diseases are related to many factors, such as human metabolism, endocrine system, immune function, and genetics, we cannot neglect important factors that affect cell structure and function, resulting in intracellular chemical changes [
2].
Maintenance of intracellular chemical homeostasis is highly relevant to human health. However, there is a lack of studies on how changes in the intracellular chemical microenvironment affect cellular structure and function, as well as the occurrence, diagnosis, and treatment of diseases. Currently, the common approach to studying complex diseases involves identifying critical signaling molecules of signaling pathways and developing a small-molecule chemical or biological drug for their targeted effects. However, the microscopic real world in the cells is a complex network of interactions between many molecules or drug-target interactions, which requires a suitable and stable chemical microenvironment in the cells [
3]. Disruption of the chemical microenvironment may alter the interaction between certain molecules, thereby affecting the normal biological information and energy transmission in the cells, leading to the imbalance of cellular homeostasis and the onset of diseases.
In 2002, Anton [
4] proposed the biological description of the relevant and dynamic changes of substances in organisms. There are different field effects on the body, and we believe that the interaction between intracellular compounds requires a suitable chemical microenvironment [
5]. For example, proteins are the most unstable at their isoelectric point environment, where they display the lowest solubility and the tendency to form aggregates. The interaction of signal molecules depends on the
and ion concentration in their microenvironment. Based on the above observations, here we introduce the concept of the cellular chemical field. This refers to the chemical microenvironment with a certain buffering capacity formed by various chemical changes in cells, which is necessary for the time-dependent dynamic network interactions of multi-omics substances within the cells. This facilitates the exchange of substances, information, and energy inside and outside the cells, which in turn sustains the functional and structural stability of the cells (
Fig. 1). We refer to the cellular chemical field as a "field," because, akin to physics, the chemical microenvironment within cells exhibits field-like characteristics. Specifically, the cellular chemical field can facilitate the transformation of energy, momentum, and mass under specific conditions [
6]. Numerous intracellular and extracellular factors can influence and regulate the cellular chemical field. Consequently, the cellular chemical field may allow us to comprehend the onset and progression of diseases from a new perspective. This allows for the evaluation of the human body’s health through the lens of a steady-state balance in the process of cytochemical change, ultimately providing a novel pathway for precise disease diagnosis and treatment.
3. Elements of the cellular chemical field
The homeostasis of the body’s chemical environment is essential for maintaining human physiological functions [
7]. The human body operates as a complete dynamic balance system, in which a part is related to others and affects the whole, and vice versa. Cells, which are the basic units of an organism, also need a stable chemical environment to maintain their structural stability and functional performance. This chemical environment, or chemical field, is influenced by various factors that affect its steady state. In this paper, we summarize the factors such as the intracellular chemical environmental polarity, ion concentration,
, and osmotic pressure, which are the constituent elements of the cellular chemical field.
3.1. Intracellular chemical environmental polarity
Intracellular chemical environmental polarity refers to the solubility or affinity characteristics of a solvent or medium for polar molecules or ions [
8]. This affects the intermolecular forces of solvents or media in the chemical field, as well as the molecular motion state of solutes or media, which are essential for the smooth exchange of substances, energy, and information inside and outside the cells.
Intracellular chemical environmental polarity is influenced by several factors [
9]. First, different types and proportions of molecules in the environment form a mixture of variable polarities. Second, changes in temperature and pressure in the environment affect the distance and motion state between molecules, thereby influencing the interaction force between molecules. An increase in temperature or a decrease in pressure results in an increased distance between molecules, allowing for freer movement, weakening the interaction force, and reducing environmental polarity. Conversely, a decrease in temperature or an increase in pressure results in a reduced distance between molecules, restricted movement, strengthened interaction force, and increased environmental polarity. Third, changes in electric and magnetic fields in the environment usually make nonpolar or weakly polar molecules more polar, or strongly polar molecules more asymmetric, thereby increasing environmental polarity.
Various methods have been employed to detect and analyze the environmental polarity, including electrical and chemical approaches. The electrical method assesses environmental polarity by using electrical parameters such as current, voltage, resistance, capacitance, and inductance. This method commonly employs electrical methods of encompassed resistivity [
10], induced polarization [
11], and dielectric constant. In contrast, the chemical method measures environmental polarity by examining the solubility, adsorption, fluorescence intensity, and other chemical properties of different compounds within various polar media. Typical chemical methods include solubility, adsorption, and fluorescence [
12].
3.2. Electrolytes
Electrolytes are compounds that exhibit electrical conductivity when dissolved in an aqueous or molten state. Electrolyte balance is the chemical basis for ensuring the stability of intracellular osmotic pressure, which is vital for maintaining normal cell function and metabolism. Electrolytes include cations, such as sodium, potassium, calcium, and magnesium, and anions, such as phosphorus and chlorine. Generally, in intracellular electrolytes, the total count of anions is equal to that of cations; thus, the electrical neutrality is maintained within a specified range. However, when there is an abnormal quantity of any electrolyte, the electrolyte balance is disrupted, hampering molecular interaction and leading to varying degrees of functional disorders and structural changes in the cells. Electrolyte disorders play a crucial role in the pathogenesis of numerous diseases [
13].
The main factors affecting electrolyte balance are as follows. ① Ion channels: Cellular metabolism necessitates a continuous exchange of substances with the surrounding environment. Ion channels on the cell membrane are essential conduits for substance exchange between the cells’ interior and exterior. These channels play a critical role in regulating the influx and efflux of specific ions, thereby preserving cell function. ② Aquaporin: Aqua-porin is a specialized, selective protein that exclusively permits the transport of water molecules through the cell membrane and does not allow the passage of charged protons or other ions. Consequently, the transport of water across the cell membrane directly affects the concentration of sodium ions within the cells [
14].
Intracellular electrolytes can be detected through various methods, such as fluorescent probes [
15], microelectrodes [
16], and patch clamp [
17]. Fluorescent probes selectively bind with specific ions, and the concentration of target ions is quantified by measuring the fluorescence intensity. This method allows for precise determination of ion concentration. Microelectrodes, which are tiny electrodes that can be delicately inserted into cells to measure the concentration of specific ions, exhibit selectivity for ions and generate electrical signals proportionate to the ion concentration, thus being valuable tools for ion analysis. The patch clamp technique provides two distinct modes, namely voltage clamp and current clamp. In the voltage clamp mode, the device sustains the cell transmembrane potential at a certain value through the negative feedback circuit, thereby enabling the observation of changes in the transmembrane current. Conversely, in the current clamp mode, a microelectrode injects a constant or varying current into the cell, thereby facilitating the recording of alterations in the corresponding membrane potential, such as the initiation of action potentials.
3.3. Potential of hydrogen
, a crucial quantitative indicator of acidity or alkalinity of a solution, is mathematically defined as the negative logarithm of hydrogen ion concentration
[
18].
plays a pivotal role in maintaining the cellular chemical environment in a state of equilibrium. Indeed, cellular
directly influences the exchange of substances and energy both within and outside the cells, and affects the dynamic balance of molecular interactions. Theoretically, any disruption in intracellular acid-base balance significantly influences various biological processes, including epigenetic modification, gene transcription, the stability of biomacromolecules’ conformation, and material metabolism.
Several factors, such as the ion transport system and intracellular ion concentrations, affect
level. Notably, within the Golgi apparatus,
regulation is governed by three key systems, namely the vacuolar adenosine triphosphatase (V-ATPase), counter ion
or
transport, and proton "leakage" pathways responsible for transporting protons from the Golgi apparatus cavity back to the cytoplasm. Furthermore, the presence of
, and
plays a role in this intricate process [
19⇓-
21].
Multiple techniques are available for measuring intracellular
(pHi) and extracellular
. The techniques encompass
sensitive nuclear magnetic resonance spectroscopy [
22], positron emission tomography [
23], radioactive tracers, magnetic resonance imaging [
24], optical imaging [
25], and diverse electrochemical sensors. Notably, Anderson et al. [
26] have pioneered the development of a novel pH-sensitive fluorescent dye, seminaph-tharhodafluor (SNARF)-which can be localized on the cell surface to determine the cell surface
in tissues ex vivo. In addition, glass nanopore technology offers a nanoscale syringe for single-cell analysis, thereby enabling precise assessment of
and single molecules through various nanopores with different pore sizes.
3.4. Osmotic pressure
Osmotic pressure pertains to the additional pressure necessary for preserving the osmotic equilibrium between the solvent and pure solvent, allowing only the solvent to permeate through the membrane [
27]. Furthermore, intracellular osmolality is influenced by ion concentration, protein concentration, and water balance. Small molecules-such as ions-contribute to crystal osmolality, while macromolecules-such as proteins-constitute colloidal osmolality. The regulation of ion and protein concentration governs the osmotic pressure in both intracellular and extracellular fluids. Keeping the osmotic pressure of intracellular and extracellular fluids approximately equal is crucial for maintaining the normal morphology and function of the cells. When there is a discrepancy in ion concentration on the two sides of the membrane, osmotic phenomena can occur, leading to the transmembrane transport of water molecules and resulting in dehydration or edema. Therefore, the change in intracellular fluid osmotic pressure can reflect the homeostasis of the intracellular chemical field.
Intracellular osmolality can be determined using a freezing point osmometer [
28] by leveraging the freezing point’s characteristics to reduce the osmotic pressure of water; the sample is mixed with an equal volume of pure water, diluting the solution, and hence equating its osmotic pressure with that of pure water.
3.5. Correlation of the chemical-field elements
The biological processes require cells to provide appropriate ion concentrations, level, osmotic pressure, and intracellular chemical environment polarity. The author believes that the occurrence and development of diseases, including cellular energy metabolism disorders, and the abnormalities of ion channel structure or function, intracellular signal transduction, gene transcription, biological macromolecular assembly, and intracellular molecular interaction relate to the steady-state imbalance of the intracellular chemical field. The first phenotypic characteristics of cell abnormalities may present as imbalance of the steady-state intracellular chemical field, which aggravates the abnormal cell metabolism and further chemical-field manifestation, thereby forming a vicious cycle. It is clear that these hypotheses need to be confirmed through systematic and in-depth studies.
According to a study published in Cell in 2008 [
29], the loss of cell polar protein, Scribble, leads the cells to the uncontrolled division and proliferation, thereby resulting in malignant transformation and cancer promotion. Anions provide electrons, while cations obtain electrons, and polar bonds strengthen the uneven distribution of electrons, making it easy to create more acidic or more alkali environments by changing the polarity of the intracellular chemical environment or undergoing chemical reactions. To prevent the cells from acidosis, the
produced by glycolysis needs to be released to the extracellular environment. The increase in
leads to the acidification of the extracellular environment, providing conditions for the invasion and metastasis of cancer cells. High acidic microenvironment is commonly found in tumor tissues, usually in areas lacking oxygen. The
level of the cellular microenvironment may have reference values for diagnosing and treating malignant tumors. As first demonstrated in 2019 by Rohani et al. from MIT [
30], acidity can trigger variable splicing of Mena invasion isoform (Mena
) and cluster of differentiation 44 (CD44), revealing that tumor acidosis promotes molecular expression related to cell invasion and metastasis. The reprogramming in response to intracellular reactions with decreased extracellular
enables cancer cells to survive and proliferate in low-
environments. An acidic environment also promotes tumor cells to produce proteins that make them more aggressive. As reported in Ref. [
31], changes in potassium ion concentration can influence the therapeutic effect of immunotherapy. The activity of anaerobic enzymes is enhanced within tumor cells, leading to accumulation of intermediate metabolites and an increase of intracellular osmotic pressure, which cause a series of physiological changes resulting in cell death.
4. Influence and regulation of chemical field on cell function and metabolism
Tumor cells show significant differences in metabolism compared with normal cells. Indeed, tumor cells adopt a different metabolic mechanism to maintain the high synthetic metabolic needs. If the chemical field required for the synthetic metabolism can be artificially intervened, it may be a novel strategy for cancer treatment. According to Ref. [
32], cellular metabolism is a key factor in maintaining the vitality and function of cancer and immune cells. Tumor metabolism itself can limit the surveillance of immune checkpoints to tumor cells, thereby ensuring immune escape and cancer survival. Therefore, understanding the metabolic requirements and their effects on intracellular chemical conditions, including the immune response to cancer, is crucial. This can selectively regulate immune cell function and treat cancer. Future perspectives should focus on targeting regulation of the intracellular chemical field for precise diagnosis and disease treatment.
4.1. Intracellular chemical environmental polarity
Alterations in intracellular chemical environmental polarity have a profound impact on various cellular biochemical processes such as material metabolism, energy conversion, and signal transduction. These changes influence the distribution of charges, electromagnetic field, and spectral characteristics of substances in the chemical field, subsequently affecting the transmission of various physical signals within the cells. These physical signals, in turn, play a crucial role in cell-cell communication, intracellular signal transduction, gene expression regulation, and other essential cellular processes. Moreover, variations in environmental polarity can induce conformational changes in the chemical-field components, thereby affecting the activities and functions of diverse biomole-cules within cells.
Changes in environmental polarity within cells can disrupt the equilibrium of the chemical field. An increase in environmental polarity results in an elevated potential difference across the cell membrane, which influences the opening and closing of ion channels in the cell membrane and, subsequently, ion concentration and
levels both inside and outside the cells. These changes disrupt intracellular signal transduction, gene expression, enzymatic reactions, and other biochemical processes, ultimately affecting cell function, such as proliferation, differentiation, migration, and apoptosis [
33].
4.2. Electrolytes
An imbalance in electrolytes can disrupt the intracellular chemical field’s homeostasis, leading to cell metabolism disorder, alterations in cell membrane potential, and changes in cell volume. Furthermore, protein synthesis and metabolism may be altered, potentially hastening cell apoptosis or cell death [
34].
The disparity in cation concentrations between the intracellular and extracellular environments is a critical factor in maintaining the cell membrane potential [
35]. The primary intracellular cation is potassium ion [
36], and both a deficiency and an excess of potassium ions can significantly affect cell function [
37,
38]. Disturbance in calcium ions can affect the electrical potential on both sides of the cell membrane, disrupt chemical-field homeostasis, and impair nerve-muscle conduction functions [
39]. Magnesium ions, which are stored in the mitochondria, are essential cofactors in carbohydrate and fat metabolism. When magnesium level is disturbed, the energy generation process, especially adenosine triphosphate synthesis, is interrupted. The resulting cellular energy deficiencies may progress to cell dysfunction or even cell death [
40]. Additionally, the discharge of intracellular calcium ions relies on the assistance of magnesium ions. Insufficient concentration of magnesium ions can impede calcium efflux, potentially causing cellular damage or eventually cell death due to excessive stimulation [
41].
4.3. Potential of hydrogen
Alterations in the
of the cellular chemical field affect the ioniization state of substances and protein structure, subsequently influencing biochemical processes within the cells. For example, the equilibrative nucleoside transporter 3 (ENT3), which is responsible for transporting hydrophilic nucleosides across cellular membranes, serves as an acid-dependent lysosomal transporter essential for nucleotide synthesis and purinergic signal transduction. A study conducted by Rahman et al. [
42] revealed that the transport activity of ENT3 was strongly pH-dependent, with the highest activity occurring at
5.5. Imbalances in acid-base conditions can result in the deactivation of critical cellular processes. The ionization state of Asp-219 and Glu-447 determines the pH-dependent activation state of the transporter ENT3. Consequently, changes in
of the chemical field can inactivate or even deactivate the ENT3 transporter’s structure, and consequently, molecular functions. Previous studies have highlighted the significance of
changes in Alzheimer disease. When
is low, amyloid-
peptide
is present within neuronal endosomes. If the
values decrease to the same level as that within endosomes, the assembly rate of
into
oligomer
is accelerated by 8000 times, resulting in the formation of amyloid fibrils [
43].
4.4. Osmotic pressure
The osmotic pressure of intracellular and extracellular fluid is normally balanced, which is essential for preserving the normal morphology and function of the cells. However, any disruption in this equilibrium leads to a shift in chemical potential. Essentially, the shift reflects the disturbance of osmotic pressure within and outside the cells, interfering with the movement of electrolytes and causing a homeostasis imbalance within the cell’s chemical field. This change in intracellular osmolarity significantly affects the activity of cellular proteins. For example, it has been shown that an intracellular hypertonic solution can accelerate the inactivation of
aquaporin expressed in Xenopus oocytes. In addition, intracellular osmolarity has a profound inhibitory effect on the intracellular current associated with the recovery of protein activity [
44]. Another study has demonstrated that increased intracellular
concentration and osmotic pressure can enhance the homologous to E6AP carboxyl terminus (HECT) family E3 neural precursor cell expressed developmentally downregulated 4-2 (Nedd4-2)/Nedd4L activity, underlining the critical role of E3 ubiq-uitination ligase activity in cell functions [
45].
Mammalian cells maintain their volume by carefully regulating intracellular osmolarity-a crucial process for early embryonic development. Previous studies have shown that early preimplanta-tion mouse embryos rely on the accumulation of intracellular glycine to establish osmotic support and manage cell volume. During ovulation-induced meiotic maturation, the glycine transporter 1 (GLYT1) facilitates glycine accumulation in mouse embryos and potentially in human embryos as well [
46,
47]. Furthermore, during gastrulation, the osmotic pressure in interstitial fluid can influence the differentiation of progenitor cells into various cell types by regulating cell surface tension. These regulatory effects are conducive to maintaining the homeostasis of the chemical field within and outside the cells.
5. Cells sensitive to the changes in the cellular chemical field
The cells sensitive to the changes in the cellular chemical field probably have active metabolic proliferation-such as germ cells, stem cells, embryonic cells, liver cells, epithelial cells, and tumor cells. Therefore, studying biological processes such as embryonic development, malignant tumor growth, and tissue regeneration should consider the factors that influence and regulate the cellular chemical field. For example, the changes in amino acid metabolism are clinical indicators of disease progression and can serve as therapeutic strategies for diseases. As reported in Ref. [
48], amino acid metabolism may be closely related to the steady-state of the cellular chemical field. In addition, through the regulation of the neurohumoral endocrine system, the chemical environment of extracellular fluid is maintained in a stable state, and the intracellular chemical field is regulated and maintained through cell membrane receptor signal transduction, ion channel gating, and exchange of intracellular and extracellular substances.
6. Application value of the chemical field in disease diagnosis and treatment
Changes in intracellular environmental polarity can serve as a detectable phenotype of chemical-field homeostasis to reflect the cells’ functional status and pathological changes. For example, nanoparticles can be engineered to bind with specific ligands, leveraging changes in the intracellular environment’s polarity to enhance cellular uptake. This strategy can enhance the targeting, stability, and bioavailability of anti-infective drugs. Utilizing a tailored chemical-field environment, it is feasible to achieve controlled drug release, effectively combat intracellular pathogens, improve therapeutic outcomes, and reduce side effects [
6]. For example, some nanocarriers can degrade or dissociate in acidic or reductive intracellular environments, thereby facilitating the release of drugs and improving the treatment of certain diseases [
49,
50]. With the rapid advancements in nanotechnology and bioengineering, novel diagnostic and therapeutic approaches grounded in the conditions of the intracellular chemical field will continue to emerge.
Electrolytes play a crucial role in preserving chemical equilibrium both inside and outside the body’s cells. The severity of certain diseases may be primarily attributed to the extent of associated intracellular electrolyte imbalance [
51]. Intracellular electrolyte irregularities can also serve as hallmarks of the early or concealed stages of certain diseases.
Intracellular
serves as a critical parameter in the characterization of cellular chemical-field homeostasis. Precisely regulating intracellular
may offer an effective approach to treat specific diseases. Notably, the intracellular
of cancer cells differs from that of normal cells. In non-cancer tissues, the
and
typically measure 7.2 and 7.5, respectively. However, in cancer tissues,
is elevated to 7.5, and
ranges from 6.4 to 7.1 [
52,
53]. The acidic microenvironment of cancer tissue and intracellular compartments has emerged as a focal point for imaging and treatment strategies [
54]. Indeed, the
of the cell microenvironment holds significant relevance in cancer diagnosis and treatment. Intracellular acid-base imbalances are a common factor in breast cancer. The
exchanger 1 (NHE1) stands out as a key pH-regulating protein that enhances proton efflux from breast cancer cells [
55]. Increased NHE1 activity results in intracellular alkalinization and extracellular acidification, thereby promoting cancer progression [
56]. To prevent acidosis, cancer must expel the excess hydrogen ions produced by glycolysis into the extracellular space. The acidification of the extracellular environment creates conditions conducive to cancer cell invasion and metastasis. In contrast, regulation of the cancer cell
may inhibit the advancement of metastatic cellular phenotypes and reduce resistance to multiple chemotherapeutic drugs.
7. Conclusions and prospective
This paper presents a novel concept for applying the cellular chemical field in basic and clinical research, including drug development and precision medicine.
Most diseases stem from regional changes in certain organs, which are often caused by cell metabolic abnormalities. Hence, examining the changes in cell function and structure through the lens of the imbalances in intracellular chemical-field homeostasis may open new avenues for both basic and clinical research. The first identifiable sign of intracellular metabolic abnormalities is often the disruption of intracellular chemical-field homeostasis. The disruption tends to exacerbate cellular metabolic dysregula-tion, creating a harmful cycle. The initial triggers for the imbalance in the cellular chemical-field homeostasis, such as regional extracellular homeostasis imbalances, cellular hypoxia, and disruptions in energy metabolism, result from microcirculatory disruption in organs. In the concealed or early stages of regional organ-related diseases, early disease diagnosis and intervention can be achieved by monitoring alterations in the cellular chemical environment. This entails the establishment and realization of an early disease warning system to restore intracellular chemical equilibrium promptly.
Exploring the principles governing changes in the cellular chemical field and understanding the mechanisms of its equilibrium hold profound biological significance and practical application. With the rapid development of computer science and technology and bioengineering technology, we can employ the theory and technology of cellular chemical field to advance research in human life, health, and disease. Currently, the detection of the cellular chemical field mainly relies on techniques such as fluorescent probes or nano-sensors, but these methods have certain limitations. For example, fluorescent probes can potentially disrupt the intracellular environment or be subjected to metabolic degradation, while nano-sensors may induce cytotoxicity or immune reactions. Consequently, there is an urgent need for the creation of more innovative, intelligent, sensitive, and high-resolution single-cell chemical-field detection technologies. These innovations are essential to enable real-time, dynamic, and quantitative monitoring of various chemicals within cells. Moreover, these technologies can be integrated with digital information models, utilizing machine-learning or deep-learning methods for the analysis and prediction of the cellular chemical field data. Enhancing intelligence, sensitivity, resolution, and other aspects will optimize existing detection methods, unveiling the intricate relationship between the cellular chemical field and cell function and structure, and allow for the estimation of the onset and progression of diseases.
A promising application of the cellular chemical field is to develop polar molecular compounds that can be selectively introduced into cells to regulate intracellular chemical homeostasis. Taking tumor as an example, abnormal activation of protein tyrosine kinases (PTKs) caused by various factors can disturb cell function, leading to abnormal growth and carcinogenesis, while inhibition of abnormal PTK function can suppress tumor growth. At present, tyrosine-kinase inhibitors (TKIs), specific inhibitors of PTKs, have been used for targeted therapy of malignant tumors. However, the drug resistance greatly limits the efficacy of TKIs. The underlying mechanisms of the failure of TKIs in cancer treatment have been summarized in a review published in Signal Transduction and Targeted Therapy in 2023 [
57]. The authors believe that it may be due to the imbalance of chemical-field homeostasis in the target cancer cells after long-term medication and the weakening of chemical binding between TKIs and the targets. If the treatment is based on the theory of chemical-field homeostasis and targets the regulation of the intracellular chemical balance rather than a simple protein, it may reverse the resistance to TKIs.
Currently, the application of the cellular chemical field is primarily confined to in vitro or animal models, which only offers partial simulations of the complex physiological and pathological states within the human body. Hence, it is imperative to extend the reach of the cellular chemical field to comprehensively assess human functional status and disease risk. This can be accomplished by amalgamating the cellular chemical field with single-cell detection technology and human bioengineering advancements. Employing three-dimensional models of human organoids, bioprinting, and microfluidic technologies, it is possible to visualize and quantify the cellular chemical fields within human organs or tissues. This allows for a thorough and precise evaluation of human health, facilitating personalized diagnoses and alternative treatment methods.
Acknowledgments
We sincerely thank Prof. Chi Chiu Wang (The Chinese University of Hong Kong, China), Miss. Tsz Ching Yeung (The Chinese University of Hong Kong, China), Miss. Wui Tin Justto Li (University of Tasmania Medical School, Australia) for the language improvement that significantly optimized our manuscript.
This work was supported by the Major Program (82293651) and the Key Program (82130055) of National Natural Science Foundation of China, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-055), and the ‘‘Pioneer” and ‘‘Leading Goose” Research and Development (R&D) Program of Zhejiang (2023C03004).
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