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1.
Bull Exp Biol Med ; 177(4): 427-430, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39259465

ABSTRACT

We studied the effect of intramuscular injection of physostigmine and neostigmine on Na+,K+-ATPase activity in erythrocytes of rats subjected to intense physical exercise. Both anticholinesterase drugs had a significant effect on the development of the stress response, which was expressed in a decrease in the manifestation of its individual components such as the concentration of ascorbic acid in the adrenal glands, stress-related erythrocyte polycythemia, and LPO indicators. Anticholinesterase drugs reverse the stress-induced decrease in Na+,K+-ATPase activity, as well as changes in its magnesium-dependent properties. There were no changes in the activity of the studied enzyme in the erythrocyte ghosts. We associate the observed differences with the correction of the functions of the cholinergic components of the hypothalamic-pituitary-adrenal axis leading to the development of a hypoergic type stress reaction.


Subject(s)
Cholinesterase Inhibitors , Erythrocytes , Neostigmine , Physical Conditioning, Animal , Physostigmine , Rats, Wistar , Sodium-Potassium-Exchanging ATPase , Animals , Sodium-Potassium-Exchanging ATPase/metabolism , Rats , Cholinesterase Inhibitors/pharmacology , Erythrocytes/drug effects , Erythrocytes/enzymology , Erythrocytes/metabolism , Male , Physostigmine/pharmacology , Neostigmine/pharmacology , Stress, Physiological/drug effects , Ascorbic Acid/pharmacology , Lipid Peroxidation/drug effects , Adrenal Glands/drug effects , Adrenal Glands/metabolism , Adrenal Glands/enzymology , Erythrocyte Membrane/drug effects , Erythrocyte Membrane/metabolism
2.
J Nanobiotechnology ; 22(1): 593, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39343894

ABSTRACT

By inhibiting acetylcholinesterase (AChE) activity, organophosphate compounds (OPs) can quickly cause severe injury to the nervous system and death, making it extremely difficult to rescue victims after OP exposure. However, it is quite challenging to construct scavengers that neutralize and eliminate these harmful chemical agents promptly in the blood circulation system. Herein, we report an enzyme-armed biomimetic nanoparticle that enables a 'targeted binding and catalytic degradation' action mechanism designed for highly efficient in vivo detoxification (denoted as 'Nanocleaner'). Specifically, the resulting Nanocleaner is fabricated with polymeric cores camouflaged with a modified red blood cell membrane (RBC membrane) that is inserted with the organophosphorus hydrolase (OPH) enzyme. In such a subtle construct, Nanocleaner inherits abundant acetylcholinesterase (AChE) on the surface of the RBC membrane, which can specifically lure and neutralize OPs through biological binding. The OPH enzyme on the membrane surface breaks down toxicants catalytically. The in vitro protective effects of Nanocleaner against methyl paraoxon (MPO)-induced inhibition of AChE activity were validated using both preincubation and competitive regimens. Furthermore, we selected the PC12 neuroendocrine cell line as an experimental model and confirmed the cytoprotective effects of Nanocleaner against MPO. In mice challenged with a lethal dose of MPO, Nanocleaner significantly reduces clinical signs of intoxication, rescues AChE activity and promotes the survival rate of mice challenged with lethal MPO. Overall, these results suggest considerable promise of enzyme-armed Nanocleaner for the highly efficient removal of OPs for clinical treatment.


Subject(s)
Acetylcholinesterase , Cholinesterase Inhibitors , Organophosphorus Compounds , Animals , Acetylcholinesterase/metabolism , Mice , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Rats , Organophosphorus Compounds/chemistry , Erythrocyte Membrane , PC12 Cells , Paraoxon/toxicity , Paraoxon/analogs & derivatives , Nanoparticles/chemistry , Aryldialkylphosphatase/metabolism , Aryldialkylphosphatase/chemistry , Male , Organophosphate Poisoning/drug therapy
3.
Parasitol Res ; 123(9): 311, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39222092

ABSTRACT

Striking morphological transformations characterize the invasion of a red blood cell by the malaria parasite. Shortly after the infection, parasite-induced membranes appear in the cytosol of the affected host erythrocyte. One intensely investigated membrane type, commonly called Maurer's clefts, has a slit-like morphology and can be arranged in the form of extended three-dimensional membrane stacks or networks. Here we report the three-dimensional reconstruction of a second membrane type, giant or extended membrane rings/loops, that have only occasionally been described on single ultrathin sections, however that have never been systematically examined so far. Serial ultrathin sectioning of P. falciparum-infected red blood cells, subsequent three-dimensional reconstructions, and in addition examination of Giemsa-stained blood films revealed that intraerythrocytic membrane rings/loops are not isolated structures but are locally in contact with the parasite. They consist either of the parasitophorous vacuolar membrane alone or contain the parasitophorous vacuolar membrane including the plasma membrane of the parasite and small amounts of parasite cytoplasm. We demonstrate that membrane rings/loops represent surface extensions of the parasite that maybe involved in ring stage parasite formation and Maurer's cleft generation at least in a subset of infected red blood cells.


Subject(s)
Cytosol , Erythrocytes , Plasmodium falciparum , Erythrocytes/parasitology , Plasmodium falciparum/physiology , Cytosol/parasitology , Cytosol/chemistry , Humans , Erythrocyte Membrane/parasitology , Erythrocyte Membrane/ultrastructure , Malaria, Falciparum/parasitology , Imaging, Three-Dimensional , Cell Membrane/parasitology
4.
Int J Pharm ; 665: 124658, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39236775

ABSTRACT

Erythrocytes have gained popularity as a natural option for in vivo drug delivery due to their advantages, which include lengthy circulation times, biocompatibility, and biodegradability. Consequently, the drug's pharmacokinetics and pharmacodynamics in red blood cells can be considerably up the dosage. Here, we provide an overview of the erythrocyte membrane's structure and discuss the characteristics of erythrocytes that influence their suitability as carrier systems. We also cover current developments in the erythrocyte-based nanocarrier, which could be used for both active and passive targeting of disease tissues, particularly those of the reticuloendothelial system (RES) and cancer tissues. We also go over the most recent discoveries about the in vivo and in vitro uses of erythrocytes for medicinal and diagnostic purposes. Moreover, the clinical relevance of erythrocytes is discussed in order to improve comprehension and enable the potential use of erythrocyte carriers in the management of various disorders.


Subject(s)
Drug Carriers , Erythrocytes , Humans , Erythrocytes/metabolism , Erythrocytes/drug effects , Drug Carriers/chemistry , Animals , Drug Delivery Systems/methods , Erythrocyte Membrane/metabolism , Nanoparticles
5.
Mar Drugs ; 22(8)2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39195451

ABSTRACT

Aquaporins (AQPs) are a family of integral membrane proteins that selectively transport water and glycerol across the cell membrane. Because AQPs are involved in a wide range of physiological functions and pathophysiological conditions, AQP-based therapeutics may have the broad potential for clinical utility, including for disorders of water and energy balance. However, AQP modulators have not yet been developed as suitable candidates for clinical applications. In this study, to identify potential modulators of AQPs, we screened 31 natural products by measuring the water and glycerol permeability of mouse erythrocyte membranes using a stopped-flow light scattering method. None of the tested natural compounds substantially affected the osmotic water permeability. However, several compounds considerably affected the glycerol permeability. Stichoposide C increased the glycerol permeability of mouse erythrocyte membranes, whereas rhizochalin decreased it at nanomolar concentrations. Immunohistochemistry revealed that AQP7 was the main aquaglyceroporin in mouse erythrocyte membranes. We further verified the effects of stichoposide C and rhizochalin on aquaglyceroporins using human AQP3-expressing keratinocyte cells. Stichoposide C, but not stichoposide D, increased AQP3-mediated transepithelial glycerol transport, whereas the peracetyl aglycon of rhizochalin was the most potent inhibitor of glycerol transport among the tested rhizochalin derivatives. Collectively, stichoposide C and the peracetyl aglycon of rhizochalin might function as modulators of AQP3 and AQP7, and suggests the possibility of these natural products as potential drug candidates for aquaglyceroporin modulators.


Subject(s)
Aquaglyceroporins , Glycerol , Animals , Mice , Aquaglyceroporins/metabolism , Humans , Glycerol/metabolism , Water/chemistry , Water/metabolism , Erythrocyte Membrane/drug effects , Erythrocyte Membrane/metabolism , Aquaporin 3/metabolism , Keratinocytes/drug effects , Keratinocytes/metabolism , Biological Transport/drug effects , Aquaporins/metabolism , Cell Membrane Permeability/drug effects
6.
Nutrients ; 16(16)2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39203842

ABSTRACT

Many patients with irritable bowel syndrome (IBS) have a compromised intestinal barrier associated with low-grade inflammation. Polyunsaturated fatty acids (PUFAs) are potential mediators of inflammation: omega-6 PUFAs are pro-inflammatory, while omega-3 PUFAs are antioxidant and anti-inflammatory. Zonulin is a potential biomarker for small intestinal permeability (s-IP). This study investigated the relationship between PUFAs and gastrointestinal (GI) barrier integrity in IBS patients with predominant diarrhea (IBS-D). We evaluated GI barrier function indicators in the urine and bloodstream and erythrocyte membrane PUFA composition in 38 IBS-D patients (5 men, 33 women, 44.11 ± 1.64 years), categorized at baseline by fecal zonulin levels into high (≥107 ng/mL, H-FZ) and normal (<107 ng/mL N-FZ) groups. Evaluations were conducted prior to and following a 12-week diet low in FODMAPs (LFD). At baseline, H-FZ patients had s-IP significantly higher than the reference value, lower n-3 PUFAs levels, and higher n-6/n-3 PUFAs and arachidonic acid (AA) to eicosapentaenoic acid (EPA) ratios than N-FZ. After LFD, H-FZ patients showed significant increases in n-3 PUFAs levels; decreases in n-6 PUFAs, n-6/n-3 PUFAs and AA/EPA ratios; and improved s-IP. The n-6/n-3 PUFAs ratio positively correlated with fecal zonulin levels in all subjects. These findings highlight the relationship between PUFAs and the intestinal barrier, suggesting their role in IBS-D pathophysiology and confirming the positive effects of LFD in managing IBS-D.


Subject(s)
Biomarkers , Diarrhea , Erythrocyte Membrane , Haptoglobins , Irritable Bowel Syndrome , Humans , Female , Irritable Bowel Syndrome/diet therapy , Male , Adult , Diarrhea/etiology , Haptoglobins/metabolism , Biomarkers/urine , Erythrocyte Membrane/metabolism , Erythrocyte Membrane/chemistry , Middle Aged , Permeability , Feces/chemistry , Fatty Acids, Omega-3/analysis , Fatty Acids, Unsaturated/analysis , Protein Precursors/metabolism , Intestinal Mucosa/metabolism , Cholera Toxin , FODMAP Diet
7.
ACS Appl Mater Interfaces ; 16(35): 46578-46589, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39172072

ABSTRACT

Atherosclerosis (AS) is characterized by the accumulation of lipids within the walls of coronary arteries, leading to arterial narrowing and hardening. It serves as the primary etiology and pathological basis for cardiovascular diseases affecting the heart and brain. However, conventional pharmacotherapy is constrained by inadequate drug delivery and pronounced toxic side effects. Moreover, the inefficacy of nanomedicine delivery systems in controlling disease progression may be attributed to nonspecific clearance by the mononuclear phagocyte system. Thus, a biomimetic platform spontaneously enveloped by red blood cell membrane is exploited for anti-atherosclerosis applications, offering favorable biocompatibility. The CLIKKPF polypeptide is introduced to develop red blood cell membrane spontaneously encapsulated nanotherapeutics only through simple coincubation. Given the functional modifications, RBC@P-LVTNPs is beneficial to facilitate the target drug delivery to the atherosclerotic lesion, responding precisely to the pathological ROS accumulation, thereby accelerating the on-demand drug release. Both in vivo and in vitro results also confirm the significant therapeutic efficacy and favorable biocompatibility of the biomimetic nanomedicine delivery system, thus providing a promising candidate for nanotherapeutics against AS.


Subject(s)
Atherosclerosis , Erythrocyte Membrane , Phosphatidylserines , Erythrocyte Membrane/chemistry , Erythrocyte Membrane/drug effects , Atherosclerosis/drug therapy , Atherosclerosis/pathology , Animals , Phosphatidylserines/chemistry , Phosphatidylserines/metabolism , Humans , Mice , Prodrugs/chemistry , Prodrugs/pharmacology , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Male
8.
ACS Nano ; 18(39): 26614-26630, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39174015

ABSTRACT

Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. Although the BRD4 inhibitor JQ1 has powerful antifibrosis properties, its clinical application is extremely limited due to its side effects. There remains an unmet need for effective, safe, and low-cost treatments. Here, we present a multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) assembled by platelet membranes and erythrocyte membranes for targeted JQ1 delivery in treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of the erythrocyte membrane enhances the long-term circulation ability of the formulated nanoparticles. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release, achieving excellent antifibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of the fusion membrane biomimetic nanodrug carrier system effectively reduced fibroblast activation, collagen secretion, and improved cardiac fibrosis. Moreover, it significantly mitigated the toxic and side effects of long-term JQ1 treatment on the liver, kidney, and intestinal tract. Mechanically, bioinformatics prediction and experimental validation revealed that PM&EM/JQ1 NPs reduced liver and kidney damage via alleviated oxidative stress and mitigated cardiac fibrosis via the activation of oxidative phosphorylation activation. These results highlight the potential value of integrating native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system for treating cardiac fibrosis and preventing drug side effects.


Subject(s)
Biomimetic Materials , Blood Platelets , Erythrocyte Membrane , Heart Failure , Nanoparticles , Triazoles , Animals , Nanoparticles/chemistry , Heart Failure/drug therapy , Mice , Erythrocyte Membrane/chemistry , Erythrocyte Membrane/drug effects , Erythrocyte Membrane/metabolism , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Blood Platelets/drug effects , Blood Platelets/metabolism , Triazoles/chemistry , Triazoles/pharmacology , Azepines/chemistry , Azepines/pharmacology , Fibrosis , Mice, Inbred C57BL , Male , Drug Delivery Systems , Humans
9.
Sci Rep ; 14(1): 15789, 2024 07 09.
Article in English | MEDLINE | ID: mdl-38982195

ABSTRACT

Red blood cells (RBCs) express the nucleic acid-binding toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs express other nucleic acid-binding TLRs is unknown. Here we show that human RBCs express the RNA sensor TLR7. TLR7 is present on the red cell membrane and is associated with the RBC membrane protein Band 3. In patients with SARS-CoV2-associated sepsis, TLR7-Band 3 interactions in the RBC membrane are increased when compared with healthy controls. In vitro, RBCs bind synthetic ssRNA and RNA from ssRNA viruses. Thus, RBCs may serve as a previously unrecognized sink for exogenous RNA, expanding the repertoire of non-gas exchanging functions performed by RBCs.


Subject(s)
COVID-19 , Erythrocytes , SARS-CoV-2 , Toll-Like Receptor 7 , Humans , Toll-Like Receptor 7/metabolism , Toll-Like Receptor 7/genetics , Erythrocytes/metabolism , COVID-19/virology , COVID-19/metabolism , SARS-CoV-2/metabolism , Sepsis/metabolism , Sepsis/blood , Sepsis/genetics , Erythrocyte Membrane/metabolism , Male , RNA/metabolism , RNA/genetics , Female
10.
PLoS One ; 19(7): e0307757, 2024.
Article in English | MEDLINE | ID: mdl-39074116

ABSTRACT

Feline chronic enteropathies (FCE), include food-responsive-enteropathy (FRE), inflammatory bowel disease (IBD), and low-grade intestinal T-cell lymphoma (LGITL), and are common causes of chronic gastrointestinal signs in cats. Distinguishing between different subgroups of FCE can be challenging due to the frequent overlap of anamnestic, clinical, and laboratory data. While dysregulation in lipid metabolism has been reported in humans and dogs with chronic IBD, similar changes in cats are not yet completely understood. Assessing the fatty acid (FA) profile of red blood cell (RBC) membranes offers a valuable method for evaluating the quantity and quality of structural and functional molecular components in the membranes. Therefore, this study aimed to examine the FA composition of RBC membranes in FCE in comparison to healthy cats (HC). Gas-chromatography was used to quantitatively analyze a cluster of 11 FA, and based on these results, parameters of lipid homeostasis and enzyme activity indexes were calculated. A total of 41 FCE cats (17 FRE, 15 IBD, 9 LGITL) and 43 HC were enrolled. In FCE cats, the values of docosapentaenoic acid (p = 0.0002) and docosahexaenoic acid (p = 0.0246), were significantly higher, resulting in an overall increase in ω-3 polyunsaturated fatty acids (PUFA) (p = 0.006), and that of linoleic acid (p = 0.0026) was significantly lower. Additionally, FCE cats exhibited an increased PUFA balance (p = 0.0019) and Δ6-desaturase index (p = 0.0151), along with a decreased ω-6/ω-3 ratio (p = 0.0019). No differences were observed among cats affected by FRE, IBD and LGITL. Like humans and dogs, the results of this study indicate that FCE cats also display changes in their FA lipid profile at the level of the RBC membrane. The non-invasive analysis of RBC membrane shows promise as a potential tool for gaining a better understanding of lipid imbalances in this disease.


Subject(s)
Cat Diseases , Erythrocyte Membrane , Fatty Acids , Inflammatory Bowel Diseases , Animals , Cats , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/veterinary , Inflammatory Bowel Diseases/blood , Fatty Acids/metabolism , Erythrocyte Membrane/metabolism , Cat Diseases/metabolism , Cat Diseases/blood , Male , Female , Lipidomics/methods , Intestinal Diseases/veterinary , Intestinal Diseases/metabolism , Intestinal Diseases/pathology , Lymphoma, T-Cell/veterinary , Lymphoma, T-Cell/metabolism , Lymphoma, T-Cell/pathology , Intestinal Neoplasms/metabolism , Intestinal Neoplasms/veterinary , Intestinal Neoplasms/pathology
11.
Molecules ; 29(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38999046

ABSTRACT

Sea buckthorn and Japanese knotweed are known in many traditional medicine systems to be a great source of bioactive substances. This research aims to compare the bioactivity and protective effects of the phenolic extracts of leaves from sea buckthorn and roots and leaves from the Japanese knotweed on erythrocytes. The polyphenol composition of the extract was analyzed using UPLC-PDA-ESI-MS/MS. The extracts' toxicity and impact on the erythrocytes' osmotic fragility were measured spectrophotometrically. The antioxidant activity was determined based on the inhibition of oxidation of erythrocytes and their membrane induced by 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH),measured spectrophotometrically and using fluorimetry. To find the possible mechanism of the extracts' action, extract-modified cells were observed under a microscope, and the potential localization of the extract's phytochemical composition was checked using fluorescent probes. The results showed that the used extracts are not toxic to erythrocytes, increase their osmotic resistance, and successfully protect them against free radicals. Extract components localize on the outer part of the membrane, where they can scavenge the free radicals from the environment. Altogether, the presented extracts can greatly protect living organisms against free radicals and can be used to support the treatment of diseases caused by excess free radicals.


Subject(s)
Erythrocyte Membrane , Hippophae , Plant Extracts , Polyphenols , Hippophae/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Polyphenols/pharmacology , Polyphenols/chemistry , Erythrocyte Membrane/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Plant Leaves/chemistry , Animals , Protective Agents/pharmacology , Protective Agents/chemistry , Erythrocytes/drug effects , Erythrocytes/metabolism , Osmotic Fragility/drug effects
12.
ACS Appl Mater Interfaces ; 16(28): 35898-35911, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38954799

ABSTRACT

Alzheimer's disease (AD) has a complex etiology and diverse pathological processes. The therapeutic effect of single-target drugs is limited, so simultaneous intervention of multiple targets is gradually becoming a new research trend. Critical stages in AD progression involve amyloid-ß (Aß) self-aggregation, metal-ion-triggered fibril formation, and elevated reactive oxygen species (ROS). Herein, red blood cell membranes (RBC) are used as templates for the in situ growth of cerium oxide (CeO2) nanocrystals. Then, carbon quantum dots (CQDs) are encapsulated to form nanocomposites (CQD-Ce-RBC). This strategy is combined with photothermal therapy (PTT) for AD therapy. The application of RBC enhances the materials' biocompatibility and improves immune evasion. RBC-grown CeO2, the first application in the field of AD, demonstrates outstanding antioxidant properties. CQD acts as a chelating agent for copper ions, which prevents the aggregation of Aß. In addition, the thermal effect induced by near-infrared laser-induced CQD can break down Aß fibers and improve the permeability of the blood-brain barrier. In vivo experiments on APP/PS1 mice demonstrate that CQD-Ce-RBC combined with PTT effectively clears cerebral amyloid deposits and significantly enhances learning and cognitive abilities, thereby retarding disease progression. This innovative multipathway approach under light-induced conditions holds promise for AD treatment.


Subject(s)
Alzheimer Disease , Cerium , Erythrocyte Membrane , Quantum Dots , Alzheimer Disease/drug therapy , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Animals , Cerium/chemistry , Cerium/pharmacology , Mice , Erythrocyte Membrane/chemistry , Quantum Dots/chemistry , Quantum Dots/therapeutic use , Humans , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/chemistry , Infrared Rays , Carbon/chemistry , Carbon/pharmacology , Photothermal Therapy , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Nanocomposites/chemistry , Nanocomposites/therapeutic use
13.
Neuroimage ; 296: 120666, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38830440

ABSTRACT

Direct imaging of semi-solid lipids, such as myelin, is of great interest as a noninvasive biomarker of neurodegenerative diseases. Yet, the short T2 relaxation times of semi-solid lipid protons hamper direct detection through conventional magnetic resonance imaging (MRI) pulse sequences. In this study, we examined whether a three-dimensional ultrashort echo time (3D UTE) sequence can directly acquire signals from membrane lipids. Membrane lipids from red blood cells (RBC) were collected from commercially available blood as a general model of the myelin lipid bilayer and subjected to D2O exchange and freeze-drying for complete water removal. Sufficiently high MR signals were detected with the 3D UTE sequence, which showed an ultrashort T2* of ∼77-271 µs and a short T1 of ∼189 ms for semi-solid RBC membrane lipids. These measurements can guide designing UTE-based sequences for direct in vivo imaging of membrane lipids.


Subject(s)
Erythrocyte Membrane , Magnetic Resonance Imaging , Membrane Lipids , Myelin Sheath , Humans , Magnetic Resonance Imaging/methods , Myelin Sheath/chemistry , Erythrocyte Membrane/chemistry , Erythrocyte Membrane/metabolism , Membrane Lipids/chemistry , Freeze Drying , Erythrocytes/metabolism
14.
Eur J Nucl Med Mol Imaging ; 51(12): 3532-3544, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38867107

ABSTRACT

PURPOSE: Fluorescence imaging-guided surgery has been used in oncology. However, for tiny tumors, the current imaging probes are still difficult to achieve high-contrast imaging, leading to incomplete resection. In this study, we achieved precise surgical resection of tiny metastatic cancers by constructing an engineering erythrocyte membrane-camouflaged bioprobe (AR-M@HMSN@P). METHODS: AR-M@HMSN@P combined the properties of aggregation-induced emission luminogens (AIEgens) named PF3-PPh3 (P), with functional erythrocyte membrane modified by a modular peptide (AR). Interestingly, AR was composed of an asymmetric tripodal pentapeptide scaffold (GGKGG) with three appended modulars: KPSSPPEE (A6) peptide, RRRR (R4) peptide and cholesterol. To verify the specificity of the probe in vitro, SKOV3 cells with overexpression of CD44 were used as the positive group, and HLF cells with low expression of CD44 were devoted as the control group. The AR-M@HMSN@P fluorescence imaging was utilized to provide surgical guidance for the removal of micro-metastatic lesions. RESULTS: In vivo, the clearance of AR-M@HMSN@P by the immune system was reduced due to the natural properties inherited from erythrocytes. Meanwhile, the A6 peptide on AR-M@HMSN@P was able to specifically target CD44 on ovarian cancer cells, and the electrostatic attraction between the R4 peptide and the cell membrane enhanced the firmness of this targeting. Benefiting from these multiple effects, AR-M@HMSN@P achieved ultra-precise tumor imaging with a signal-to-noise ratio (SNR) of 15.2, making it possible to surgical resection of tumors < 1 mm by imaging guidance. CONCLUSION: We have successfully designed an engineered fluorescent imaging bioprobe (AR-M@HMSN@P), which can target CD44-overexpressing ovarian cancers for precise imaging and guide the resection of minor tumors. Notably, this work holds significant promise for developing biomimetic probes for clinical imaging-guided precision cancer surgery by exploiting their externally specified functional modifications.


Subject(s)
Erythrocyte Membrane , Fluorescent Dyes , Ovarian Neoplasms , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/surgery , Female , Humans , Fluorescent Dyes/chemistry , Erythrocyte Membrane/chemistry , Cell Line, Tumor , Animals , Precision Medicine/methods , Optical Imaging/methods , Surgery, Computer-Assisted/methods , Mice , Hyaluronan Receptors/metabolism
15.
Adv Sci (Weinh) ; 11(29): e2310230, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38837643

ABSTRACT

Blood transfusions save lives and improve health every day. Despite the matching of blood types being stricter than it ever has been, emergency transfusions among incompatible blood types are still inevitable in the clinic when there is a lack of acceptable blood types for recipients. Here to overcome this, a counter measure nanoplatform consisting of a polymeric core coated by a red blood cell (RBC) membrane is developed. With A-type or B-type RBC membrane camouflaging, the nanoplatform is capable of specifically capturing anti-A or anti-B IgM antibodies within B-type or A-type whole blood, thereby decreasing the corresponding IgM antibody levels and then allowing the incompatible blood transfusions. In addition to IgM, the anti-RBC IgG antibody in a passive immunization murine model can likewise be neutralized by this nanoplatform, leading to prolonged circulation time of incompatible donor RBCs. Noteworthily, nanoplatform made by expired RBCs (>42 days stored hypothermically) and then subjected to lyophilization does not impair their effect on antibody neutralization. Most importantly, antibody-captured RBC-NP do not exacerbate the risk of inflammation, complement activation, and coagulopathy in an acute hemorrhagic shock murine model. Overall, this biomimetic nanoplatform can safely neutralize the antibody to enable incompatible blood transfusion.


Subject(s)
Erythrocyte Membrane , Nanoparticles , Animals , Mice , Erythrocyte Membrane/immunology , Blood Transfusion/methods , Disease Models, Animal , Humans , Erythrocytes/immunology , Blood Group Incompatibility/immunology
16.
Colloids Surf B Biointerfaces ; 241: 114017, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38865869

ABSTRACT

Inspired by the "natural camouflage" strategy, cell-based biomimetic drug delivery systems (BDDS) have shown great potential in cancer therapy. Red blood cell (RBC) delivery vehicles and red blood cell membrane (RBCm)-camouflaged vehicles were commonly used strategies for drug delivery. We prepared shikonin-encapsulated PLGA nanoparticles (PLGA/SK) with different surface charges to obtain both RBC delivery and RBCm-camouflaged PLGA NPs. The physicochemical properties, in vivo circulation and antitumor effects of these biomimetic preparations were studied. Since the positive PLGA NPs may affect the morphology and function of RBCs, the biomimetic preparations prepared by the negative PLGA NPs showed better in vitro stability. However, positive PLGA NP-based biomimetic preparations exhibited longer circulation time and higher tumor region accumulation, leading to stronger anti-tumor effects. Meanwhile, the RBC delivery PLGA(+) NPs possessed better in vitro cytotoxicity, longer circulation time and higher tumor accumulation than RBCm-camouflaged PLGA(+) NPs. Collectively, RBC delivery vehicles possessed more potential than RBCm-camouflaged vehicles on drug delivery for tumor treatment, especially with positive NPs-loaded.


Subject(s)
Colorectal Neoplasms , Drug Delivery Systems , Nanoparticles , Naphthoquinones , Polylactic Acid-Polyglycolic Acid Copolymer , Naphthoquinones/chemistry , Naphthoquinones/pharmacology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Nanoparticles/chemistry , Animals , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Humans , Mice , Erythrocytes/drug effects , Cell Membrane/drug effects , Cell Membrane/chemistry , Cell Membrane/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Cell Survival/drug effects , Particle Size , Cell Line, Tumor , Cell Proliferation/drug effects , Mice, Inbred BALB C , Erythrocyte Membrane/chemistry
17.
Nanoscale ; 16(25): 11863-11878, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38841898

ABSTRACT

Red blood cells (RBCs), which function as material transporters in organisms, are rich in materials that are exchanged with metabolically active tumor cells. Recent studies have demonstrated that tumor cells can regulate biological changes in RBCs, including influencing differentiation, maturation, and morphology. RBCs play an important role in tumor development and immune regulation. Notably, the novel scientific finding that RBCs absorb fragments of tumor-carrying DNA overturns the conventional wisdom that RBCs do not contain nucleic acids. RBC membranes are excellent biomimetic materials with significant advantages in terms of their biocompatibility, non-immunogenicity, non-specific adsorption resistance, and biodegradability. Therefore, RBCs provide a new research perspective for the development of tumor liquid biopsies, molecular imaging, drug delivery, and other tumor precision diagnosis and treatment technologies.


Subject(s)
Erythrocytes , Neoplasms , Humans , Erythrocytes/metabolism , Neoplasms/therapy , Neoplasms/diagnosis , Neoplasms/pathology , Precision Medicine , Animals , Drug Delivery Systems , Erythrocyte Membrane/chemistry , Erythrocyte Membrane/metabolism , Biomimetic Materials/chemistry
18.
Nutrients ; 16(12)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38931154

ABSTRACT

Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments. Diseases accompanying psoriasis include metabolic and cardiovascular disorders. It has been suggested that inflammation is involved in the development of each of these conditions. The main objective of this study was to analyse the fatty acid profile, including polyunsaturated fatty acids, in the erythrocyte membranes of patients suffering from psoriasis. A total of 58 adult patients of the Department of Skin and Venereal Diseases of the Pomeranian Medical University in Szczecin, suffering from psoriasis, were qualified for this study. The patients had undergone an interview and physical examination, during which the severity of psoriasis was assessed. All patients had their weight and height measured to assess their body mass index (BMI). After 3 months of treatment, biochemical parameters (ALT, AST, total cholesterol) and inflammatory markers (CRP) in the blood were assessed. In addition, the isolation of fatty acids (PUFAs, SFAs, MUFAs) from erythrocyte membranes and the qualitative and quantitative analysis of their profile using a gas chromatograph were carried out. In patients with severe psoriasis requiring systemic treatment, an altered profile of fatty acids in erythrocyte membranes was found, including a significantly lower concentration of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a significantly higher concentration of saturated fatty acids; and a decreased concentration of oleic acid (omega-9), compared to the results obtained in patients with less severe psoriasis receiving topical treatment. In patients with psoriasis and BMI ≥ 25, significantly higher concentrations of AST and ALT in the blood and significantly higher concentrations of pro-inflammatory arachidonic acid in erythrocyte membranes were found. Elevated concentrations of saturated (R = 0.31) and monounsaturated fatty acids (R = 0.29) may correlate with a greater severity of psoriasis.


Subject(s)
Erythrocyte Membrane , Fatty Acids , Psoriasis , Humans , Psoriasis/blood , Erythrocyte Membrane/metabolism , Erythrocyte Membrane/chemistry , Female , Male , Middle Aged , Fatty Acids/blood , Adult , Body Mass Index , Fatty Acids, Unsaturated/blood , Severity of Illness Index , Biomarkers/blood , Aged
19.
Molecules ; 29(11)2024 May 27.
Article in English | MEDLINE | ID: mdl-38893395

ABSTRACT

High concentrations of acrolein (2-propenal) are found in polluted air and cigarette smoke, and may also be generated endogenously. Acrolein is also associated with the induction and progression of many diseases. The high reactivity of acrolein towards the thiol and amino groups of amino acids may cause damage to cell proteins. Acrolein may be responsible for the induction of oxidative stress in cells. We hypothesized that acrolein may contribute to the protein damage in erythrocytes, leading to the disruption of the structure of cell membranes. The lipid membrane fluidity, membrane cytoskeleton, and osmotic fragility were measured for erythrocytes incubated with acrolein for 24 h. The levels of thiol, amino, and carbonyl groups were determined in cell membrane and cytosol proteins. The level of non-enzymatic antioxidant potential (NEAC) and TBARS was also measured. The obtained research results showed that the exposure of erythrocytes to acrolein causes changes in the cell membrane and cytosol proteins. Acrolein stiffens the cell membrane of erythrocytes and increases their osmotic sensitivity. Moreover, it has been shown that erythrocytes treated with acrolein significantly reduce the non-enzymatic antioxidant potential of the cytosol compared to the control.


Subject(s)
Acrolein , Cytosol , Erythrocyte Membrane , Erythrocytes , Acrolein/pharmacology , Acrolein/toxicity , Acrolein/metabolism , Cytosol/metabolism , Cytosol/drug effects , Erythrocytes/drug effects , Erythrocytes/metabolism , Humans , Erythrocyte Membrane/drug effects , Erythrocyte Membrane/metabolism , Oxidative Stress/drug effects , Antioxidants/pharmacology , Antioxidants/metabolism , Membrane Proteins/metabolism , Cell Membrane/metabolism , Cell Membrane/drug effects , Membrane Fluidity/drug effects , Osmotic Fragility/drug effects
20.
Bull Exp Biol Med ; 176(6): 811-815, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38896317

ABSTRACT

The qualitative composition and zeta potential of magnetite nanoparticles (size 4.2±1.2 nm) obtained by co-precipitation method were determined by X-ray and diffraction dynamic light scattering. The zeta potential of Fe3O4 particles was -15.1±4.5 mV. The possibility of interaction of magnetite nanoparticles with human blood plasma proteins and hemoglobin as well as with erythrocyte membranes was demonstrated by spectrophotometry, electrophoresis, and fluorescence methods. No changes in the sizes of hemoglobin molecules and plasma proteins after their modification by Fe3O4 particles were detected. The possibility of modifying the structural state of erythrocyte membranes in the presence of magnetite nanoparticles was demonstrated by means of fluorescent probe 1-anilinonaphthalene-8-sulfonate.


Subject(s)
Hemoglobins , Magnetite Nanoparticles , Humans , Magnetite Nanoparticles/chemistry , Hemoglobins/chemistry , Erythrocyte Membrane/drug effects , Erythrocyte Membrane/chemistry , Erythrocyte Membrane/metabolism , Particle Size , Blood Proteins/chemistry , Anilino Naphthalenesulfonates/chemistry , X-Ray Diffraction , Ferrosoferric Oxide/chemistry , Fluorescent Dyes/chemistry
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