Trastuzumab-functionalized bionic pyrotinib liposomes for targeted therapy of HER2-positive breast cancer.

In this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.

Nanoghosts: Harnessing Mesenchymal Stem Cell Membrane for Construction of Drug Delivery Platforms Via Optimized Biomimetics.

Mesenchymal stem cells (MSCs) are becoming hotspots for application in disease therapies recently, combining with biomaterials and drug delivery system. A major advantage of MSCs applied in drug delivery system is that these cells enable specific targeting and releasing of cargos to the disease sites. However, the potential tumor tropic effects of MSCs raised concerns on biosafety. To solve this problem, there are emerging methods of isolating cell membranes and developing nanoformulations to perform drug delivery, which avoids concerns on biosafety without disturbing the membrane functions of specific polarizing and locating. These cargoes are so called "nanoghosts." This review article summarizes the current applications of nanoghosts, the promising potential of MSCs to be applied in membrane isolation and nanoghost construction, and possible approaches to develop better drug delivery system harnessing from MSC ghost cell membranes.

Dual siRNA-Loaded Cell Membrane Functionalized Matrix Facilitates Bone Regeneration with Angiogenesis and Neurogenesis.

Vascularization and innervation play irreplaceable roles in bone regeneration and bone defect repair. However, the reconstruction of blood vessels and neural networks is often neglected in material design. This study aims to design a genetically functionalized matrix (GFM) and enable it to regulate angiogenesis and neurogenesis to accelerate the process of bone defect repair. The dual small interfering RNA (siRNA)-polyvinylimide (PEI) (siRP) complexes that locally knocked down soluble vascular endothelial growth factor receptor 1 (sFlt-1) and p75 neurotrophic factor receptor (p75NTR ) are prepared. The hybrid cell membrane (MM) loaded siRP is synthesized as siRNA@MMs to coat on polylactone (PCL) electrospun fibers for mimicking the natural bone matrix. The results indicates that siRNA@MMs could regulate the expression of vascular-related and neuro-related cytokines secreted by mesenchymal stem cells (MSCs). GFMs promote the expression of osteogenic differentiation through paracrine function in vitro. GFMs attenuates inflammation and promotes osseointegration by regulating the coupling of vascularization and innervation in vivo. This study uses the natural hybrid cell membrane to carry genetic material and assist in the vascularization and innervation function of two siRNA. The results present the significance of neuro-vascularized organoid bone and may provide a promising choice for the design of bone tissue engineering scaffold.

Cancer Cell Membrane-Based Materials for Biomedical Applications.

The nanodelivery system provides a novel direction for disease diagnosis and treatment; however, its delivery effectiveness is restricted by the short biological half-life and inadequate tumor targeting. The immune evasion properties and homologous targeting capabilities of natural cell membranes, particularly those of cancer cell membranes (CCM), have gained significant interest. The integration of CCM and nanoparticles has resulted in the emergence of CCM-based nanoplatforms (CCM-NPs), which have gained significant attention due to their unique properties. CCM-NPs not only prolong the blood circulation time of core nanoparticles, but also direct them for homologous tumor targeting. Herein, the history and development of CCM-NPs as well as how these platforms have been used for biomedical applications are discussed. The application of CCM-NPs for cancer therapy will be described in detail. Translational efforts are currently under way and further research to address key areas of need will ultimately be required to facilitate the successful clinical adoption of CCM-NPs.

Recent Advances of Engineered Cell Membrane-Based Nanotherapeutics to Combat Inflammatory Diseases.

An immune reaction known as inflammation serves as a shield from external danger signals, but an overactive immune system may additionally lead to tissue damage and even a variety of inflammatory disorders. By inheriting biological functionalities and serving as both a therapeutic medication and a drug carrier, cell membrane-based nanotherapeutics offer the potential to treat inflammatory disorders. To further strengthen the anti-inflammatory benefits of natural cell membranes, researchers alter and optimize the membranes using engineering methods. This review focuses on engineered cell membrane-based nanotherapeutics (ECMNs) and their application in treating inflammation-related diseases. Specifically, this article discusses the methods of engineering cell membranes for inflammatory diseases and examines the progress of ECMNs in inflammation-targeted therapy, inflammation-neutralizing therapy, and inflammation-immunomodulatory therapy. Additionally, the article looks into the perspectives and challenges of ECMNs in inflammatory treatment and offers suggestions as well as guidance to encourage further investigations and implementations in this area.

M2 Macrophage Membrane-Camouflaged Fe3 O4 -Cy7 Nanoparticles with Reduced Immunogenicity for Targeted NIR/MR Imaging of Atherosclerosis.

Atherosclerosis （AS） is the primary reason behind cardiovascular diseases, leading to approximately one-third of global deaths. Developing a novel multi-model probe to detect AS is urgently required. Macrophages are the primary cells from which AS genesis occurs. Utilizing natural macrophage membranes coated on the surface of nanoparticles is an efficient delivery method to target plaque sites. Herein, Fe3 O4 -Cy7 nanoparticles (Fe3 O4 -Cy7 NPs), functionalized using an M2 macrophage membrane and a liposome extruder for Near-infrared fluorescence and Magnetic resonance imaging, are synthesized. These macrophage membrane-coated nanoparticles (Fe3 O4 @M2 NPs) enhance the recognition and uptake using active macrophages. Moreover, they inhibit uptake using inactive macrophages and human coronary artery endothelial cells. The macrophage membrane-coated nanoparticles (Fe3 O4 @M0 NPs, Fe3 O4 @M1 NPs, Fe3 O4 @M2 NPs) can target specific sites depending on the macrophage membrane type and are related to C-C chemofactor receptor type 2 protein content. Moreover, Fe3 O4 @M2 NPs demonstrate excellent biosafety in vivo after injection, showing a significantly higher Fe concentration in the blood than Fe3 O4 -Cy7 NPs. Therefore, Fe3 O4 @M2 NPs effectively retain the physicochemical properties of nanoparticles and depict reduced immunological response in blood circulation. These NPs mainly reveal enhanced targeting imaging capability for atherosclerotic plaque lesions.

Clonal hematopoiesis and acquired genetic abnormalities of the red cell: An historical review.

Several syndromes affecting the red cell that mimic those induced by germline mutations may result from a somatic mutation that accompanies a myeloid malignancy. These syndromes are most notable in cases of myelodysplastic syndrome, but they are not limited to any one category of myeloid neoplasm. Their occurrence in males exceed the male predominance that is evident in myeloid neoplasms. The syndromes include disorders of globin chain synthesis (α- and ß-thalassemia), heme synthesis (erythropoietic porphyria and erythropoietic uroporphyria), red cell membrane structure (elliptocytosis and spherocytosis), red cell enzyme activity (pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency) and lowered expression of red cell ABO blood group antigens. This historical review describes the path to uncovering these acquired syndromes and their causal somatic mutations, where known. These syndromes often go unrecognized because of the dominant concern of the primary neoplasm. They may add to the healthcare needs of the patient.

Discovery in space of ethanolamine, the simplest phospholipid head group.

Cell membranes are a key element of life because they keep the genetic material and metabolic machinery together. All present cell membranes are made of phospholipids, yet the nature of the first membranes and the origin of phospholipids are still under debate. We report here the presence of ethanolamine in space, [Formula: see text]OH, which forms the hydrophilic head of the simplest and second-most-abundant phospholipid in membranes. The molecular column density of ethanolamine in interstellar space is N = (1.51[Formula: see text]0.07)[Formula: see text], implying a molecular abundance with respect to [Formula: see text] of [Formula: see text] Previous studies reported its presence in meteoritic material, but they suggested that it is synthesized in the meteorite itself by decomposition of amino acids. However, we find that the proportion of the molecule with respect to water in the interstellar medium is similar to the one found in the meteorite ([Formula: see text]). These results indicate that ethanolamine forms efficiently in space and, if delivered onto early Earth, could have contributed to the assembling and early evolution of primitive membranes.

Autophagy and Symbiosis: Membranes, ER, and Speculations.

The interaction of plants and soil bacteria rhizobia leads to the formation of root nodule symbiosis. The intracellular form of rhizobia, the symbiosomes, are able to perform the nitrogen fixation by converting atmospheric dinitrogen into ammonia, which is available for plants. The symbiosis involves the resource sharing between two partners, but this exchange does not include equivalence, which can lead to resource scarcity and stress responses of one of the partners. In this review, we analyze the possible involvement of the autophagy pathway in the process of the maintenance of the nitrogen-fixing bacteria intracellular colony and the changes in the endomembrane system of the host cell. According to in silico expression analysis, ATG genes of all groups were expressed in the root nodule, and the expression was developmental zone dependent. The analysis of expression of genes involved in the response to carbon or nitrogen deficiency has shown a suboptimal access to sugars and nitrogen in the nodule tissue. The upregulation of several ER stress genes was also detected. Hence, the root nodule cells are under heavy bacterial infection, carbon deprivation, and insufficient nitrogen supply, making nodule cells prone to autophagy. We speculate that the membrane formation around the intracellular rhizobia may be quite similar to the phagophore formation, and the induction of autophagy and ER stress are essential to the success of this process.

Exploring membrane vesicles in citrus fruits: a comparative analysis of conventional and organic farming approaches.

BACKGROUND: Recently, vesicles derived from plant cell membranes have received attention for their potential use as active biomolecules and nanocarriers, and obtaining them from organic crops may be an interesting option because different farming systems can affect production, plant secondary metabolism and biochemistry of cell membranes. The present study aimed to determine how organic and conventional farming affects the mineral nutrition, gas exchange, CO2 fixation and biochemical composition of lemon fruits, which could have an impact on the different fractions of cell membranes in pulp and juice. RESULTS: Organic trees had higher intrinsic water use efficiency (WUEi) but conventional trees had higher stomatal conductance (gs) and nitrogen use efficiency (NUtE). Also, organic lemons had significantly higher levels of some micronutrients (Ca, Cu, Fe and Zn). Second, the main differences in the membrane vesicles showed that organic pulp vesicles had a higher antioxidant activity and more oleic acid, whereas both types of vesicles from conventional lemons had more linoleic acid. CONCLUSION: In conclusion, organic farming did not alter carbon fixation parameters but impacted nitrogen fixation and water uptake, and resulted in higher micronutrient levels in lemons. These mineral nutritional changes could be related to the higher production of membranes that showed suitable morphological traits and a high antioxidant activity, positively correlated with a high amount of oleic acid, which could have stronger cell protection characteristics. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

A Magnetic Resonance Imaging-Chemical Exchange Saturation Transfer (MRI-CEST) Method for the Detection of Water Cycling across Cellular Membranes.

Water cycling across the membrane transporters is considered a hallmark of cellular metabolism and it could be of high diagnostic relevance in the characterization of tumors and other diseases. The method relies on the response of intracellular proton exchanging molecules to the presence of extracellular Gd-based contrast agents (GBCAs). Paramagnetic GBCAs enhances the relaxation rate of water molecules in the extracellular compartment and, through membrane exchange, the relaxation enhancement is transferred to intracellular molecules. The effect is detected at the MRI-CEST (Magnetic Resonance Imaging - Chemical Exchange Saturation Transfer) signal of intracellular proton exchanging molecules. The magnitude of the change in the CEST response reports on water cycling across the membrane. The method has been tested on Red Blood Cells and on orthotopic murine models of breast cancer with different degree of malignancy (4T1, TS/A and 168FARN). The distribution of voxels reporting on membrane permeability fits well with the cells' aggressiveness and acts as an early reporter to monitor therapeutic treatments.

Fused-Ring Pyrrole-Based Near-Infrared Emissive Organic RTP Material for Persistent Afterglow Bioimaging.

Organic near-infrared room temperature phosphorescence (RTP) materials offer remarkable advantages in bioimaging due to their characteristic time scales and background noise elimination. However, developing near-infrared RTP materials for deep tissue imaging still faces challenges since the small band gap may increase the non-radiative decay, resulting in weak emission and short phosphorescence lifetime. In this study, fused-ring pyrrole-based structures were employed as the guest molecules for the construction of long wavelength emissive RTP materials. Compared to the decrease of the singlet energy level, the triplet energy level showed a more effectively decrease with the increase of the conjugation of the substituent groups. Moreover, the sufficient conjugation of fused ring structures in the guest molecule suppresses the non-radiative decay of triplet excitons. Therefore, a near-infrared RTP material (764 nm) was achieved for deep penetration bioimaging. Tumor cell membrane is used to coat RTP nanoparticles (NPs) to avoid decreasing the RTP performance compared to traditional coating by amphiphilic surfactants. RTP NPs with tumor-targeting properties show favorable phosphorescent properties, superior stability, and excellent biocompatibility. These NPs are applied for time-resolved luminescence imaging to eliminate background interference with excellent tissue penetration. This study provides a practical solution to prepare long-wavelength and long-lifetime organic RTP materials and their applications in bioimaging.

A marine-derived fatty acid targets the cell membrane of Gram-positive bacteria.

IMPORTANCE: With the lack of new antibiotics in the drug discovery pipeline, coupled with accelerated evolution of antibiotic resistance, new sources of antibiotics that target pathogens of clinical importance are paramount. Here, we use bacterial cytological profiling to identify the mechanism of action of the monounsaturated fatty acid (Z)-13-methyltetra-4-decenoic acid isolated from the marine bacterium Olleya marilimosa with antibacterial effects against Gram-positive bacteria. The fatty acid antibiotic was found to rapidly destabilize the cell membrane by pore formation and membrane aggregation in Bacillus subtilis, suggesting that this fatty acid may be a promising adjuvant used in combination to enhance antibiotic sensitivity.

A Survey of Two-Component Systems in Coxiella burnetii Reveals Redundant Regulatory Schemes and a Requirement for an Atypical PhoBR System in Mammalian Cell Infection.

Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of Q fever in humans. C. burnetii transitions between a replicative, metabolically active large-cell variant (LCV) and a spore-like, quiescent small-cell variant (SCV) as a likely mechanism to ensure survival between host cells and mammalian hosts. C. burnetii encodes three canonical two-component systems, four orphan hybrid histidine kinases, five orphan response regulators, and a histidine phosphotransfer protein, which have been speculated to play roles in the signaling required for C. burnetii morphogenesis and virulence. However, very few of these systems have been characterized. By employing a CRISPR interference system for genetic manipulation of C. burnetii, we created single- and multigene transcriptional knockdown strains targeting most of these signaling genes. Through this, we revealed a role for the C. burnetii PhoBR canonical two-component system in virulence, regulation of [Pi] maintenance, and Pi transport. We also outline a novel mechanism by which PhoBR function may be regulated by an atypical PhoU-like protein. We also determined that the GacA.2/GacA.3/GacA.4/GacS orphan response regulators coordinately and disparately regulate expression of SCV-associated genes in C. burnetii LCVs. These foundational results will inform future studies on the role of C. burnetii two-component systems in virulence and morphogenesis. IMPORTANCE C. burnetii is an obligate intracellular bacterium with a spore-like stability allowing it to survive long periods of time in the environment. This stability is likely due to its biphasic developmental cycle, whereby it can transition from an environmentally stable small-cell variant (SCV) to a metabolically active large-cell variant (LCV). Here, we define the role of two-component phosphorelay systems (TCS) in C. burnetii's ability to survive within the harsh environment contained in the phagolysosome of host cells. We show that the canonical PhoBR TCS has an important role in C. burnetii virulence and phosphate sensing. Further examination of the regulons controlled by orphan regulators indicated a role in modulating gene expression of SCV-associated genes, including genes essential for cell wall remodeling.

Biomimetic Nanobomb for Synergistic Therapy with Inhibition of Cancer Stem Cells.

Cancer stem cells (CSCs), a type of cell with self-renewal, unlimited proliferation, and insensitivity to common physical and chemical factors, are the key to cancer metastasis, recurrence, and chemo-resistance. Available CSCs inhibition strategies are mainly based on small molecule drugs, yet are limited by their off-target toxicity. The link between CSCs and non-CSCs interconversion is difficult to sever. In this work, a nanotherapeutic strategy based on MnOx -loaded polydopamine (MnOx /PDA) nanobombs with chemodynamic, photodynamic, photothermal and biodegradation properties to inhibit CSCs and non-CSCs concurrently is reported. The MnOx /PDA nanobombs can directly disrupt the microenvironment and tumorigenic capacity of CSCs by generating hyperthermia, oxidative stress and alleviating hypoxia. The markers of CSCs are subsequently downregulated, leading to the clearance of CSCs. Meanwhile, the synergistic therapy mediated by MnOx /PDA nanobombs can directly ablate the bulk tumor cells, thus cutting off the supply of CSCs transformation. For tumor targeting, MnOx /PDA is coated with macrophage membrane. The final tumor inhibition rate of the synergistic therapy is 70.8% in colorectal cancer (CRC) model. Taken together, the present work may open up the exploration of nanomaterial-based synergistic therapy for the simultaneous elimination of therapeutically resistant CSCs and non-CSCs.

M2 Macrophage Membrane-Mediated Biomimetic-Nanoparticle Carrying COX-siRNA Targeted Delivery for Prevention of Tendon Adhesions by Inhibiting Inflammation.

Tendon adhesion is the most common outcome of tendon or tendon-to-bone healing after injury. Our group developed a hydrogel-nanoparticle sustained-release system previously to inhibit cyclooxygenases (COXs) expression and consequently prevent tendon adhesion and achieved satisfactory results. However, effective treatment of multiple tendon adhesions is always a challenge in research on the prevention of tendon adhesion. In the present study, an M2M@PLGA/COX-siRNA delivery system is successfully constructed using the cell membranes of M2 macrophages and poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Targeting properties and therapeutic effects are observed in mice or rat models of flexor digitorum longus (FDL) tendon injury combined with rotator cuff injury. The results showed that the M2M@PLGA/COX-siRNA delivery system has low toxicity and remarkable targeting properties to the injured areas. Treatment with the M2M@PLGA/COX-siRNA delivery system reduced the inflammatory reaction and significantly improved tendon adhesion in both the FDL tendon and rotator cuff tissues. These findings indicate that the M2M@PLGA delivery system can provide an effective biological strategy for preventing multiple tendon adhesions.

The building blocks of caveolae revealed: caveolins finally take center stage.

The ability of cells to divide, migrate, relay signals, sense mechanical stimuli, and respond to stress all rely on nanoscale invaginations of the plasma membrane known as caveolae. The caveolins, a family of monotopic membrane proteins, form the inner layer of the caveolar coat. Caveolins have long been implicated in the generation of membrane curvature, in addition to serving as scaffolds for signaling proteins. Until recently, however, the molecular architecture of caveolins was unknown, making it impossible to understand how they operate at a mechanistic level. Over the past year, two independent lines of evidence - experimental and computational - have now converged to provide the first-ever glimpse into the structure of the oligomeric caveolin complexes that function as the building blocks of caveolae. Here, we summarize how these discoveries are transforming our understanding of this long-enigmatic protein family and their role in caveolae assembly and function. We present new models inspired by the structure for how caveolins oligomerize, remodel membranes, interact with their binding partners, and reorganize when mutated. Finally, we discuss emerging insights into structural differences among caveolin family members that enable them to support the proper functions of diverse tissues and organisms.

A dual-targeting near-infrared biomimetic drug delivery system for HBV treatment.

Hepatitis B virus (HBV) infection is a serious global public health threat. It remains elusive to achieve a functional HBV cure with currently available antivirals. Herein, a photo-responsive delivery vehicle composed of Nd3+ -sensitized core-shell upconversion nanoparticle (UCNP), mesoporous silica nanoparticle (MSN), antisense oligonucleotides (ASOs), and capsid-binding inhibitor C39 was established, which was named UMAC according to the initials of its components. Subsequently, the as-synthesized delivery vehicle was encapsulated by ß- D-galactopyranoside (Gal) modified red blood cell (RBC) membrane vesicles, which enabled precise targeting of the liver cells (UMAC-M-Gal). Both in vitro and in vivo experiments demonstrated that this biomimetic system could successfully achieve controlled drug release under light conditions at 808 nm, leading to effective suppression of HBV replication in this dual-targeted therapeutic approach. Together, these results substantiate the system has huge prospects for application to achieve functional HBV cure, and provides a promising novel strategy for drug delivery.

Cell membrane biomimetic nanoparticles in drug delivery.

Despite the efficiency of nanoparticle (NP) therapy, in vivo investigations have shown that it does not perform as well as in vitro. In this case, NP confronts many defensive hurdles once they enter the body. The delivery of NP to sick tissue is inhibited by these immune-mediated clearance mechanisms. Hence, using a cell membrane to hide NP for active distribution offers up a new path for focused treatment. These NPs are better able to reach the disease's target location, leading to enhanced therapeutic efficacy. In this emerging class of drug delivery vehicles, the inherent relation between the NPs and the biological components obtained from the human body was utilized, which mimic the properties and activities of native cells. This new technology has shown the viability of using biomimicry to evade immune system-provided biological barriers, with an emphasis on restricting clearance from the body before reaching its intended target. Furthermore, by providing signaling cues and transplanted biological components that favorably change the intrinsic immune response at the disease site, the NPs would be capable interacting with immune cells regarding the biomimetic method. Thus, we aimed to provide a current landscape and future trends of biomimetic NPs in drug delivery.

Research progress on the cellular toxicity caused by microplastics and nanoplastics.

Microplastics (MPs) are plastic particles of a diameter of less than 5 mm and a major carrier of pollution. In accordance with its diameter range, MPs can be divided into microplastics (100-5 mm) and nanoplastics (<100 nm). In recent years, in addition to the impact of MPs on the environment, the ways in which MPs affect the body has also attracted continuous attention. However, relevant studies on the cytotoxicity of MPs are not comprehensive. Based on the current research, this paper summarizes four main cytotoxic mechanisms of MPs, inducing oxidative stress, damaging cell membrane organelles, inducing immune response, and genotoxicity. Generally, MPs cause cytotoxicity such as oxidative stress, damage to cell membranes and organelles, activation of immune responses, and genotoxicity through mechanical damage or induction of cells to produce reactive oxygen species. Understanding these toxic mechanisms is helpful for the evaluation and prevention of human toxicity of MPs. This paper also analyzes the limitations of current research and prospects for future research into cellular MPs, with the aim of providing a scientific basis and reference for further research into the toxic mechanism of MPs.