MicroRNAs: The Master Regulators of the Breast Cancer Tumor Microenvironment

Breast cancer is the most commonly diagnosed cancer globally and is among the leading causes of cancer deaths worldwide. Breast cancer mortality rates are increasing due to delays in diagnosis, prognosis, and treatment caused by the coronavirus disease 2019 (COVID-19) pandemic. Identification and validation of blood-based breast cancer biomarkers for early detection is a top priority worldwide. MicroRNAs (miRNAs) show the potential to serve as breast cancer biomarkers. miRNAs are small, endogenously produced RNAs that regulate growth and development. However, oncogenic miRNAs also play a major role in tumor growth and can alter the tumor microenvironment (TME) in favor of cancer metastasis. The TME represents a complex network of diverse cancerous and noncancerous cell types, secretory proteins, growth factors, and miRNAs. Complex interactions within the TME can promote cancer progression and metastasis via multiple mechanisms, including oxidative stress, hypoxia, angiogenesis, lymphangiogenesis, and cancer stem cell regulation. Here, we decipher the mechanisms of miRNA regulating the TME, intending to use that knowledge to identify miRNAs as therapeutic targets in breast cancer and use miRNAs as blood-based biomarkers. © Springer Nature Singapore Pte Ltd. 2022.

[Ferroptosis-associated lesion as a potential target for cardiovascular disease: A review].

Cell death is an important feature of the development of multicellular organisms, a critical factor in the occurrence of cardiovascular diseases. Understanding the mechanisms that control cell death is crucial to determine its role in the development of the pathological process. However, the most well-known types of cell death cannot fully explain the pathophysiology of heart disease. Understanding how cardiomyocytes die and why their regeneration is limited is an important area of research. Ferroptosis is an iron-dependent cell death that differs from apoptosis, necrosis, autophagy, and other forms of cell death in terms of morphology, metabolism, and protein expression. Ferroptotic cell death is characterized by the accumulation of reactive oxygen species resulting from lipid peroxidation and subsequent oxidative stress, which can be prevented by iron chelates (eg, deferoxamine) and small lipophilic antioxidants (eg, ferrostatin, liproхstatin). In recent years, many studies have been carried out on ferroptosis in the context of the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In addition to cardiovascular diseases, the review also presents data on the role of ferroptosis in the development of other socially significant diseases, such as COVID-19, chronic obstructive pulmonary disease. With the study of ferroptosis, it turned out that ferroptosis participates in the development of bacterial infection associated with the persistence in the host body of Pseudomonas aeruginosa. The review summarizes the recent advances in the study of ferroptosis, characterizing this type of cell death as a novel therapeutic target.

Bright photon upconversion in LiYbF4:Tm3+@LiYF4 nanoparticles and their application for singlet oxygen generation and in immunoassay for SARS-CoV-2 nucleoprotein.

Photon upconversion is an intensively investigated phenomenon in the materials sciences due to its unique applications, mainly in biomedicine for disease prevention and treatment. This study reports the synthesis and properties of tetragonal LiYbF4:Tm3+@LiYF4 core@shell nanoparticles (NPs) and their applications. The NPs had sizes ranging from 18.5 to 23.7 nm. As a result of the energy transfer between Yb3+ and Tm3+ ions, the synthesized NPs show intense emission in the ultraviolet (UV) range up to 347 nm under 975 nm excitation. The bright emission in the UV range allows for singlet oxygen generation in the presence of hematoporphyrin on the surface of NPs. Our studies show that irradiation with a 975 nm laser of the functionalized NPs allows for the production of amounts of singlet oxygen easily detectable by Singlet Oxygen Sensor Green. The high emission intensity of NPs at 800 nm allowed the application of the synthesized NPs in an upconversion-linked immunosorbent assay (ULISA) for highly sensitive detection of the nucleoprotein from SARS-CoV-2, the causative agent of Covid-19. This article proves that LiYbF4:Tm3+@LiYF4 core@shell nanoparticles can be perfect alternatives for the most commonly studied upconverting NPs based on the NaYF4 host compound and are good candidates for biomedical applications.

The Impact of Serum Levels of Reactive Oxygen and Nitrogen Species on the Disease Severity of COVID-19.

Elucidation of the redox pathways in severe coronavirus disease 2019 (COVID-19) might aid in the treatment and management of the disease. However, the roles of individual reactive oxygen species (ROS) and individual reactive nitrogen species (RNS) in COVID-19 severity have not been studied to date. The main objective of this research was to assess the levels of individual ROS and RNS in the sera of COVID-19 patients. The roles of individual ROS and RNS in COVID-19 severity and their usefulness as potential disease severity biomarkers were also clarified for the first time. The current case-control study enrolled 110 COVID-19-positive patients and 50 healthy controls of both genders. The serum levels of three individual RNS (nitric oxide (NO•), nitrogen dioxide (ONO-), and peroxynitrite (ONOO-)) and four ROS (superoxide anion (O2•-), hydroxyl radical (•OH), singlet oxygen (1O2), and hydrogen peroxide (H2O2)) were measured. All subjects underwent thorough clinical and routine laboratory evaluations. The main biochemical markers for disease severity were measured and correlated with the ROS and RNS levels, and they included tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), the neutrophil-to-lymphocyte ratio (NLR), and angiotensin-converting enzyme 2 (ACE2). The results indicated that the serum levels of individual ROS and RNS were significantly higher in COVID-19 patients than in healthy subjects. The correlations between the serum levels of ROS and RNS and the biochemical markers ranged from moderate to very strongly positive. Moreover, significantly elevated serum levels of ROS and RNS were observed in intensive care unit (ICU) patients compared with non-ICU patients. Thus, ROS and RNS concentrations in serum can be used as biomarkers to track the prognosis of COVID-19. This investigation demonstrated that oxidative and nitrative stress play a role in the etiology of COVID-19 and contribute to disease severity; thus, ROS and RNS are probable innovative targets in COVID-19 therapeutics.

The inhibitory and inactivating effects of visible light on SARS-CoV-2: A narrative update.

Prior to the coronavirus disease-19 (COVID-19) pandemic, the germicidal effects of visible light (λ = 400 - 700 nm) were well known. This review provides an overview of new findings that suggest there are direct inactivating effects of visible light - particularly blue wavelengths (λ = 400 - 500 nm) - on exposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions, and inhibitory effects on viral replication in infected cells. These findings complement emerging evidence that there may be clinical benefits of orally administered blue light for limiting the severity of COVID-19. Possible mechanisms of action of blue light (e.g., regulation of reactive oxygen species) and important mediators (e.g., melatonin) are discussed.

[Research progress on the relationship between low-density neutrophils and infectious diseases]

Neutrophils play an important role in infectious diseases by clearing pathogens in the early stages of the disease and damaging the surrounding tissues along with the disease progress. Low-density neutrophils (LDNs) are a crucial and distinct subpopulation of neutrophils. They are a mixture of activated and degranulated normal mature neutrophils and a considerable number of immature neutrophils prematurely released from the bone marrow. Additionally, they may be involved in the occurrence and development of diseases through the changes in phagocytosis, the generation of reactive oxygen species (ROS), the enhancement of the ability to produce neutrophils extracellular traps and immunosuppression. We summarizes the role of LDNs in the pathogenesis and their correlation with the severity of infectious diseases such as COVID-19, severe fever with thrombocytopenia syndrome (SFTS), AIDS, and tuberculosis.

[Research progress on the relationship between low-density neutrophils and infectious diseases]

Neutrophils play an important role in infectious diseases by clearing pathogens in the early stages of the disease and damaging the surrounding tissues along with the disease progress. Low-density neutrophils (LDNs) are a crucial and distinct subpopulation of neutrophils. They are a mixture of activated and degranulated normal mature neutrophils and a considerable number of immature neutrophils prematurely released from the bone marrow. Additionally, they may be involved in the occurrence and development of diseases through the changes in phagocytosis, the generation of reactive oxygen species (ROS), the enhancement of the ability to produce neutrophils extracellular traps and immunosuppression. We summarizes the role of LDNs in the pathogenesis and their correlation with the severity of infectious diseases such as COVID-19, severe fever with thrombocytopenia syndrome (SFTS), AIDS, and tuberculosis.

[Research progress on the relationship between low-density neutrophils and infectious diseases]

Neutrophils play an important role in infectious diseases by clearing pathogens in the early stages of the disease and damaging the surrounding tissues along with the disease progress. Low-density neutrophils (LDNs) are a crucial and distinct subpopulation of neutrophils. They are a mixture of activated and degranulated normal mature neutrophils and a considerable number of immature neutrophils prematurely released from the bone marrow. Additionally, they may be involved in the occurrence and development of diseases through the changes in phagocytosis, the generation of reactive oxygen species (ROS), the enhancement of the ability to produce neutrophils extracellular traps and immunosuppression. We summarizes the role of LDNs in the pathogenesis and their correlation with the severity of infectious diseases such as COVID-19, severe fever with thrombocytopenia syndrome (SFTS), AIDS, and tuberculosis.

Oxidative DNA damage by N4-hydroxycytidine, a metabolite of the SARS-CoV-2 antiviral molnupiravir.

Molnupiravir is an antiviral agent recently used for treating COVID-19. Here, we demonstrate that N4-hydroxycytidine (NHC), a molnupiravir metabolite, treated with cytidine deaminase (CDA) induced Cu(II)-mediated oxidative DNA damage in isolated DNA. A colorimetric assay revealed hydroxylamine generation from CDA-treated NHC. The site specificity of DNA damage also suggested involvement of hydroxylamine in the damage. Furthermore, Cu(I) and H2O2 play an important role in the DNA damage. We propose oxidative DNA damage via CDA-mediated metabolism as a possible mutagenic mechanism of NHC, highlighting the need for careful risk assessment of molnupiravir use in therapies for viral diseases including COVID-19.

Functional Role of Natural Antioxidants in Controlling Oxidative Stress Associated with SARS-CoV-2 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogenic coronavirus that emerged in late 2019, resulting in coronavirus disease (COVID-19). COVID-19 can be potentially fatal among a certain group of patients. Older age and underlying medical illness are the major risk factors for COVID-19-related fatal respiratory dysfunction. The reason for the pathogenicity of COVID-19 in the older age group remains unclear. Factors, such as coagulopathy, cytokine storm, metabolic disrup-tion, and impaired T cell function, may worsen the symptoms of the disease. Recent literature has indicat-ed that viral infections are particularly associated with a high degree of oxidative stress and an imbalance of antioxidant response. Although pharmacological management has taken its place in reducing the severity of COVID-19, the antioxidants can serve as an adjunct therapy to protect an individual from oxidative damage triggered by SARS-CoV-2 infection. In general, antioxidant enzymes counteract free radicals and prevent their formation. The exact functional role of antioxidant supplements in reducing disease symptoms of SARS-CoV-2 infection remains mostly unknown. In this review, the functional role of natural antioxidants in SARS-CoV-2 infection management is discussed in brief.Copyright © 2022 Bentham Science Publishers.

Highly Twisted Conformation Thiopyrylium Photosensitizers for In Vivo Near Infrared‐II Imaging and Rapid Inactivation of Coronavirus

Despite significant effort, a majority of heavy‐atom‐free photosensitizers have short excitation wavelengths, thereby hampering their biomedical applications. Here, we present a facile approach for developing efficient near‐infrared (NIR) heavy‐atom‐free photosensitizers. Based on a series of thiopyrylium‐based NIR‐II (1000–1700 nm) dyads, we found that the star dyad HD with a sterically bulky and electron‐rich moiety exhibited configuration torsion and significantly enhanced intersystem crossing (ISC) compared to the parent dyad. The electron excitation characteristics of HD changed from local excitation (LE) to charge transfer (CT)‐domain, contributing to a ≈6‐fold reduction in energy gap (ΔEST), a ≈10‐fold accelerated ISC process, and a ≈31.49‐fold elevated reactive oxygen species (ROS) quantum yield. The optimized SP@HD‐PEG2K lung‐targeting dots enabled real‐time NIR‐II lung imaging, which precisely guided rapid pulmonary coronavirus inactivation.

The immune enhancement effect of Nelumbo nucifera Gaertner Seed Extract (NSE) in murine macrophage RAW 264.7 cells

Since the global shock caused by COVID-19, interest in immune-enhancing materials is rapidly increasing, therefore, the development of novel materials is necessary from the industrial and health perspectives. In this study, we selected Nelumbo nucifera Gaertner Seed Extract (NSE) and evaluated immune enhancement effect by using RAW 264.7 murine macrophage cells. NSE significantly up-regulated production of nitric oxide and reactive oxygen species without affecting cell viability in RAW 264.7 cells. Additionally, NSE exhibited an increase of inducible nitric oxide synthase and cyclooxygenase-2 expression in RAW 264.7 cells. The enzyme-linked immuno-sorbent assay results showed that NSE-treatment significantly enhanced production of interleukin 6 and tumor necrosis factor-α in RAW 264.7 cells. Furthermore, we observed that NSE significantly up-regulated phosphorylation of p65, I kappa B kinase α/β, and I kappa B (IκB) α as well as down-regulation of IκB α expression in RAW 264.7 cells. Our findings indicate that NSE could be the potential health-functional food material with capacity of improving immunity via Nuclear factor-kappa B signaling pathway. © 2023, Korean Society for Applied Biological Chemistry. All rights reserved.

A discussion of heat generation during a fever

Fever can be caused by pathogen infection. We analyze the thermogenesis mechanism and reveal that heat is naturally generated during the immune system's fight against pathogen infection. Particularly, the heat production by reactive oxygen species that originates in the respiratory burst significantly contributes to the fever development. This analysis can help address mechanisms of SARS-CoV-2 pathogenesis or provide a foundation for future mechanistic inquiries.Copyright © 2022, Research Trends (P) LTD.. All rights reserved.

Spike Protein Impairs Mitochondrial Function in Human Cardiomyocytes: Mechanisms Underlying Cardiac Injury in COVID-19.

BACKGROUND: COVID-19 has a major impact on cardiovascular diseases and may lead to myocarditis or cardiac failure. The clove-like spike (S) protein of SARS-CoV-2 facilitates its transmission and pathogenesis. Cardiac mitochondria produce energy for key heart functions. We hypothesized that S1 would directly impair the functions of cardiomyocyte mitochondria, thus causing cardiac dysfunction. METHODS: Through the Seahorse Mito Stress Test and real-time ATP rate assays, we explored the mitochondrial bioenergetics in human cardiomyocytes (AC16). The cells were treated without (control) or with S1 (1 nM) for 24, 48, and 72 h and we observed the mitochondrial morphology using transmission electron microscopy and confocal fluorescence microscopy. Western blotting, XRhod-1, and MitoSOX Red staining were performed to evaluate the expression of proteins related to energetic metabolism and relevant signaling cascades, mitochondrial Ca2+ levels, and ROS production. RESULTS: The 24 h S1 treatment increased ATP production and mitochondrial respiration by increasing the expression of fatty-acid-transporting regulators and inducing more negative mitochondrial membrane potential (Δψm). The 72 h S1 treatment decreased mitochondrial respiration rates and Δψm, but increased levels of reactive oxygen species (ROS), mCa2+, and intracellular Ca2+. Electron microscopy revealed increased mitochondrial fragmentation/fission in AC16 cells treated for 72 h. The effects of S1 on ATP production were completely blocked by neutralizing ACE2 but not CD147 antibodies, and were partly attenuated by Mitotempo (1 µM). CONCLUSION: S1 might impair mitochondrial function in human cardiomyocytes by altering Δψm, mCa2+ overload, ROS accumulation, and mitochondrial dynamics via ACE2.

Selenium Status and Oxidative Stress in SARS-CoV-2 Patients.

Background and Objectives: Insufficient intake of essential micronutrient selenium (Se) increases the susceptibility to diseases associated with oxidative stress. The study aim was to assess Se status and oxidative stress in COVID-19 patients depending on severity of the disease. Materials and Methods: Blood plasma of 80 post-COVID-19 disease patients and 40 acutely ill patients were investigated. Concentration of Se was detected by a fluorometric method with di-amino-naphthalene using acidic hydrolysis. Selenoprotein P (Sepp1), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) and their metabolite adducts were evaluated by spectrophotometric methods using commercial assay kits. Results: Obtained results demonstrated that Se and Sepp1 concentration in acute patients were significantly (p < 0.05 for Se and p < 0.001 for Sepp1) decreased compared with post-COVID-19 disease patients. However, in post-COVID-19 disease patients, Se values were close to the low limit of the norm for the European population. 4-HNE adducts concentration as a marker of lipid peroxidation was significantly increased in the acute patients group compared to the recovery group (p < 0.001). Conclusions: COVID-19 pathology is characterized by the induction of oxidative stress and suppression of antioxidant defenses during the acute phase. Lower levels of Se and Sepp1 and higher levels of reactive oxygen species reflect this imbalance, highlighting the role of oxidative stress in the disease's pathogenesis.

Hypoxia induces dichotomous and reversible attenuation of T cell responses through reactive oxygen species-dependent phenotype redistribution and delay in lymphoblast proliferation.

As T cells transit between blood, lymphoid organs, and peripheral tissues, they experience varied levels of oxygen/hypoxia in inflamed tissues, skin, intestinal lining, and secondary lymphoid organs. Critical illness among COVID-19 patients is also associated with transient hypoxia and attenuation of T cell responses. Hypoxia is the fulcrum of altered metabolism, impaired functions, and cessation of growth of a subset of T cells. However, the restoration of normal T cell functions following transient hypoxia and kinetics of their phenotype-redistribution is not completely understood. Here, we sought to understand kinetics and reversibility of dichotomous T cell responses under sustained and transient hypoxia. We found that a subset of activated T cells accumulated as lymphoblasts under hypoxia. Further, T cells showed the normal expression of activation markers CD25 and CD69 and inflammatory cytokine secretion but a subset exhibited delayed cell proliferation under hypoxia. Increased levels of reactive oxygen species (ROS) in cytosol and mitochondria were seen during dichotomous and reversible attenuation of T cell response under hypoxia. Cell cycle analysis revealed maximum levels of cytosolic and mitochondrial ROS in dividing T cells (in S, G2, or M phase). Hypoxic T cells also showed specific attenuation of activation induced memory phenotype conversion without affecting naïve and activated T cells. Hypoxia-related attenuation of T cell proliferation was also found to be reversible in an allogeneic leukocyte specific mixed lymphocyte reaction assay. In summary, our results show that hypoxia induces a reversible delay in proliferation of a subset of T cells which is associated with obliteration of memory phenotype and specific increase in cytosolic/mitochondrial ROS levels in actively dividing subpopulation. Thus, the transient reoxygenation of hypoxic patients may restore normal T cell responses.

Oxygen toxicity: cellular mechanisms in normobaric hyperoxia.

In clinical settings, oxygen therapy is administered to preterm neonates and to adults with acute and chronic conditions such as COVID-19, pulmonary fibrosis, sepsis, cardiac arrest, carbon monoxide poisoning, and acute heart failure. In non-clinical settings, divers and astronauts may also receive supplemental oxygen. In addition, under current standard cell culture practices, cells are maintained in atmospheric oxygen, which is several times higher than what most cells experience in vivo. In all the above scenarios, the elevated oxygen levels (hyperoxia) can lead to increased production of reactive oxygen species from mitochondria, NADPH oxidases, and other sources. This can cause cell dysfunction or death. Acute hyperoxia injury impairs various cellular functions, manifesting ultimately as physiological deficits. Chronic hyperoxia, particularly in the neonate, can disrupt development, leading to permanent deficiencies. In this review, we discuss the cellular activities and pathways affected by hyperoxia, as well as strategies that have been developed to ameliorate injury. • Hyperoxia promotes overproduction of reactive oxygen species (ROS). • Hyperoxia dysregulates a variety of signaling pathways, such as the Nrf2, NF-κB and MAPK pathways. • Hyperoxia causes cell death by multiple pathways. • Antioxidants, particularly, mitochondria-targeted antioxidants, have shown promising results as therapeutic agents against oxygen toxicity in animal models.

Systemic redox imbalance in severe COVID-19 patients.

The aim of this study was to evaluate the systemic redox state and inflammatory markers in intensive care unit (ICU) or non-ICU severe COVID-19 patients during the hospitalization period. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients), 5-7 days after admission (T2: 5-7 days after hospital admission), and at the discharge time from the hospital (T3: 0-72 h before leaving hospital or death) to analyze systemic oxidative stress markers and inflammatory variables. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were analyzed in peripheral granulocytes and monocytes. THP-1 human monocytic cell line was incubated with plasma from non-ICU and ICU COVID-19 patients and cell viability and apoptosis rate were analyzed. Higher total antioxidant capacity, protein oxidation, lipid peroxidation, and IL-6 at hospital admission were identified in both non-ICU and ICU COVID-19 patients. ICU COVID-19 patients presented increased C-reactive protein, ROS levels, and protein oxidation over hospitalization period compared to non-ICU patients, despite increased antioxidant status. Granulocytes and monocytes of non-ICU and ICU COVID-19 patients presented lower MMP and higher ROS production compared to the healthy controls, with the highest values found in ICU COVID-19 group. Finally, the incubation of THP-1 cells with plasma acquired from ICU COVID-19 patients at T3 hospitalization period decreased cell viability and apoptosis rate. In conclusion, disturbance in redox state is a hallmark of severe COVID-19 and is associated with cell damage and death.

Prussian Blue@Zeolitic imidazolate framework composite toward solar-triggered biodecontamination

Metal-organic frameworks (MOFs) featuring composition and bandstructure diversity, are an emerging class of photoresponsive disinfectants. In this study, we demonstrated the superiority of core–shell arranged photoactive MOFs (prussian blue (PB) and zeolitic imidazolate framework (ZIF-8)) for pathogen inactivation in terms of biocidal efficiency and broad-spectrum sensitivity. Reactive oxygen species (ROS) production was significantly promoted after the integration of PB due to the photosensitization effect and initiation of in situ Fenton reaction. Favorably, another inactivation channel was also opened owing to the unique photothermal effect of PB. Attributed to the facilitated ROS intracellular penetration by heat, the composite outperforms not only individual component but anatase TiO2 in pathogen elimination. Specifically, the Staphylococcus aureus (S. aureus) inactivation efficiency of the composite (6.6 log) is 2, 1.8 and 5.1 times higher than that of PB (3.3 log), ZIF-8 (3.7 log) and TiO2 (1.3 log) over 45 min of simulated sunlight illumination. Significantly, the infectivity of Bacillus anthracis and murine coronavirus in droplets on composite-coated filter surface could be greatly reduced (approximately 3 log reduction in colony number/coronavirus titer) within few minutes of solar exposure, indicative of the great potential of MOF composites toward life-threatening microbial infection prevention. © 2022 Elsevier B.V.

Antimicrobial photodynamic therapy and the advances impacted by the association with nanoparticles

Microbial resistance to antibiotics, antifungals, and virucides is one of today's most significant public health problems. Antimicrobial Photodynamic Therapy (aPDT) is a prominent therapeutic strategy for infection control that does not cause microbial resistance to treatment. Its microbial eradication potential is significantly increased when aPDT is associated with nanotechnology. aPDT causes cell death due to photophysical and photochemical events derived from the interaction between a photosensitive agent (PS), a light at an appropriate wavelength, and the oxygen in the medium. Its main product, reactive oxygen species (ROS), leads to the death of microorganisms in and around the irradiated PS. However, the low water solubility, instability, and low microbial internalization of PSs with high quantum yield diminish the effectiveness of the aPDT. Nanoparticles emerge to overcome these limitations. They have been shown to increase the photodynamic activity of PSs and potentially target their delivery to infected sites, increasing the selectivity of the therapy. This review addresses the main constraints of bacteria, fungi, and viruses to the effectiveness of aPDT and discusses how nanotechnology can overcome these difficulties. Current studies that used polymeric, lipid, and metallic nanoparticles associated with aPDT were raised, and the significant advances impacted by them were critically discussed. Among the microorganisms eliminated by nanoparticles-associated aPDT, Methicillin-Resistant Staphylococcus aureus (MRSA) bacteria in planktonic culture and the form of biofilms, and fungi such as Candida albicans, stand out. The nanoparticle-associated aPDT increases the chances of success of oral cavity treatments, such as those that affect the root canal, and cutaneous, such as dermatophytosis. The use of aPDT against viruses such as HSV-1 and HIV, including Sars-CoV-2, has also shown promising results. The selectivity and effectiveness of aPDT are strictly related to the characteristics of the PS-loaded nanoparticle. It is essential to know the microorganism and the place it is installed to select the nanocarrier properly. © 2023 Elsevier B.V.