Nano-sized Vesicles Research Articles

Exosome is a Fancy Mobile Sower of Ferroptosis.

Exosomes, nano-sized small extracellular vesicles, have been shown to serve as mediators between intercellular communications by transferring bioactive molecules, such as non-coding RNA, proteins, and lipids from secretory to recipient cells, modulating a variety of physiological and pathophysiological processes. Recent studies have gradually demonstrated that altered exosome charges may represent a key mechanism driving the pathological process of ferroptosis. This review summarizes the potential mechanisms and signal pathways relevant to ferroptosis and then discusses the roles of exosome in ferroptosis. As well as transporting iron, exosomes may also indirectly convey factors related to ferroptosis. Furthermore, ferroptosis may be transmitted to adjacent cells through exosomes, resulting in cascading effects. It is expected that further research on exosomes will be conducted to explore their potential in ferroptosis and will lead to the creation of new therapeutic avenues for clinical diseases.

A NIR-II quantum dot-assisted dual-color imaging strategy enables simultaneous tracking of two subtypes of extracellular vesicles in vivo

Extracellular vesicles (EVs) are naturally occurring nano-sized membrane-bound vesicles with remarkable heterogeneity. To effectively elucidate their various biological behaviors, it is imperative to label EVs with fluorophores. Traditional EV labeling within the visible spectrum leads to autofluorescence interference and emission wavelength limitations, hindering the study of diverse EVs and necessitating separate analyses in different subjects which affects research accuracy. In this study, we leveraged an innovative near-infrared-Ⅱ (NIR-Ⅱ) QD-assisted dual-color imaging technique to simultaneously monitor the distribution patterns of EVs in single animals, discerning differences based on size, surface proteins, and inter-vesicular interactions. We revealed that EVs smaller than 200 nm (small EVs, sEVs) predominantly localize to the spleen and lymph nodes as opposed to their larger counterparts (large EVs, lEVs, > 200 nm). This preferential positioning in peripheral immune organs for sEVs appears to be intricately linked to their surface composition, exemplified by the presence of biomolecules like programmed death-ligand 1 (PD-L1). Results also revealed that tumor cell-derived sEVs and immunocyte-derived sEVs significantly affect each other's biodistribution in vivo. In summary, present study provides a refined method for the accurate evaluation of the in vivo biological behaviors of heterogeneous EVs. This advancement is expected to deepen our understanding of EV diversity and their complex roles within biological systems.

The role of the size of affinity ligands in the detection and characterization of extracellular vesicles

Surface proteins on the membrane of nano-sized extracellular vesicles (EVs) not only play crucial roles in cell-to-cell communication, but also are specific binding targets for EV detection, isolation and tracking. The low abundance of protein biomarkers on EV surface, the formation of clusters and the complex EV surface network impose significant challenges to the study of EVs. Employing bulky sized affinity ligands, such as antibodies, in the detection and characterization of these vesicles often result in reduced sensitivity of detection or poor quantification of proteins on the EV surface. By virtue of their small size and high specificity, Affibody molecules emerge as a potential alternative to their monoclonal antibody counterparts as robust affinity ligands in EV research. In this study, we present a theoretical framework on the superiority of anti-HER2 Affibodies over anti-HER2 antibodies in labeling and detecting HER2-positive EVs, followed by the demonstration of the advantages of HER2 Affibodies in accessing EV surface and the detection of EVs through multiple types of approaches including fluorescence intensity, colorimetry, and fluorescence polarization. HER2 Affibodies outperformed by 10-fold over three HER2 antibody clones in accessing HER2-positive EVs derived from different human cancer cell lines. Furthermore, HRP-Affibody molecules could detect EVs from cancer cells spiked into human serum with at least a 2-fold higher sensitivity compared with that of their antibody counterparts. In addition, in fluorescence polarization assays in which no separation of free from bound ligand is required, FITC-labeled HER2 Affibodies could sensitively detect HER2-positive EVs with a clinically relevant limit of detection, whilst HER2 antibodies failed to detect EVs in the same conditions. With the demonstrated superiority in accessing and detecting surface targets over bulky-sized antibodies in EVs, Affibodies may become the next-generation of affinity ligands in the precise characterization and quantification of molecular architecture on the surface of EVs.

High-Performance Aluminum Fuels Induced by Monolayer Self-Assembly of Nano-Sized Energetic Fluoride Vesicles on the Surface.

Surface modification is frequently used to solve the problems of low combustion properties and agglomeration for aluminum-based fuels. However, due to the intrinsic incompatibility between the aluminum powder and the organic modifiers, the surface coating is usually uneven and disordered, which significantly deteriorates the uniformity and performances of the Al-based fuels. Herein, a new approach of monolayer nano-vesicular self-assembly is proposed to prepare high-performance Al fuels. Triblock copolymer G-F-G is produced by glycidyl azide polymer (GAP) and 2,2'-(2,2,3,3,4,5,5-Octafluorohexane-1,6-diyl) bis (oxirane) (fluoride) ring-open addition reaction. By utilizing G-F-G vesicular self-assembly in a special solvent, the nano-sized vesicles are firmly adhered to the surface of Al powder through the long-range attraction between the fluorine segments and Al. Meanwhile, the electrostatic repulsion between vesicles ensures an extremely thin coating thickness (≈15nm), maintaining the monolayer coating structure. Nice ignition, combustion, anti-agglomeration, and water-proof properties of Al@G-F-G(DMF) are achieved, which are superior among the existing Al-based fuels. The derived Al-based fuel has excellent comprehensive properties, which can not only inspire the development of new-generation energetic materials but also provide facile but exquisite strategies for exquisite surface nanostructure construction via ordered self-assembly for many other applications.

Exosomes in Atherosclerosis: Role in the Pathogenesis and Targets for Therapy.

Atherosclerotic cardiovascular disease (ASCVD) is an advanced chronic inflammatory disease and the leading cause of death worldwide. The pathological development of ASCVD begins with atherosclerosis, characterised by a pathological remodelling of the arterial wall, lipid accumulation and build-up of atheromatous plaque. As the disease advances, it narrows the vascular lumen and limits the blood, leading to ischaemic necrosis in coronary arteries. Exosomes are nano-sized lipid vesicles of different origins that can carry many bioactive molecules from their parental cells, thus playing an important role in intercellular communication. The roles of exosomes in atherosclerosis have recently been intensively studied, advancing our understanding of the underlying molecular mechanisms. In this review, we briefly introduce exosome biology and then focus on the roles of exosomes of different cellular origins in atherosclerosis development and progression, functional significance of their cargoes and physiological impact on recipient cells. Studies have demonstrated that exosomes originating from endothelial cells, vascular smooth muscle cells, macrophages, dendritic cells, platelets, stem cells, adipose tissue and other sources play an important role in the atherosclerosis development and progression by affecting cholesterol transport, inflammatory, apoptotic and other aspects of the recipient cells' metabolism. MicroRNAs are considered the most significant type of bioactive molecules transported by exosomes and involved in ASCVD development. Finally, we review the current achievements and limitations associated with the use of exosomes for the diagnosis and treatment of ASCVD.

Oxylipin profile of human milk and human milk-derived extracellular vesicles

BackgroundSmall Extracellular Vesicles (sEVs) are nano-sized vesicles that are present in all biofluids including human milk (HM) playing a crucial role in cell-to-cell communication and the stimulation of the neonatal immune system. Oxylipins, which are bioactive lipids formed from polyunsaturated fatty acids, have gained considerable attention due to their potential role in mitigating disease progression and modulating the inflammatory status of breastfed infants. This study aims at an in-depth characterization of the oxylipin profiles of HM and, for the first time, of HM-derived sEVs (HMEVs) employing an ad-hoc developed and validated ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. ResultsThe UPLC-MS/MS method covered a panel of 13 oxylipins for quantitation and 93 oxylipins for semi-quantitation. In 200 μL of HM and HMEV isolates of 15 individuals, 42 out of 106 oxylipins were detected in either HM or HMEVs, with 38 oxylipins being detected in both matrices. Oxylipins presented distinct profiles in HM and HMEVs, suggesting specific mechanisms responsible for the encapsulation of target molecules in HMEVs. Ten and eight oxylipins were quantified with ranges between 0.03 – 73 nM and 0.30 pM–0.07 nM in HM and HMEVs, respectively. The most abundant oxylipins found in HMEVs were docosahexaenoic acid derivatives (17-HDHA and 14-HDHA) with known anti-inflammatory properties, and linoleic acid derivatives (9-10-DiHOME and 12,13-DiHOME) in HM samples. Significance and noveltyThis is the first time a selective, relative enrichment of anti-inflammatory oxylipins in HMEVs has been described. Future studies will focus on the anti-inflammatory and pro-healing capacity of oxylipins encapsulated in HMEVs, with potential clinical applications in the field of preterm infant care, specifically the prevention of severe intestinal complications including necrotizing enterocolitis.

Possible Roles of Extracellular Vesicles in the Pathogenesis and Interventions of Immune-Mediated Central Demyelinating Diseases.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two of the most devastating immune-mediated central demyelinating disorders. NMOSD was once considered as a variant of MS until the discovery of an antibody specific to the condition. Despite both MS and NMOSD being considered central demyelinating disorders, their pathogenesis and clinical manifestations are distinct, however the exact mechanisms associated with each disease remain unclear. Extracellular vesicles (EVs) are nano-sized vesicles originating in various cells which serve as intercellular communicators. There is a large body of evidence to show the possible roles of EVs in the pathogenesis of several diseases, including the immune-mediated central demyelinating disorders. Various types of EVs are found across disease stages and could potentially be used as a surrogate marker, as well as acting by carrying a cargo of biochemical molecules. The possibility for EVs to be used as a next-generation targeted treatment for the immune-mediated central demyelinating disorders has been investigated. The aim of this review was to comprehensively identify, compile and discuss key findings from in vitro, in vivo and clinical studies. A summary of all findings shows that: 1) the EV profiles of MS and NMOSD differ from those of healthy individuals, 2) the use of EV markers as liquid biopsy diagnostic tools appears to be promising biomarkers for both MS and NMOSD, and 3) EVs are being studied as a potential targeted therapy for MS and NMOSD. Any controversial findings are also discussed in this review.

Canine Mesenchymal Stromal Cell Exosomes: State-of-the-Art Characterization, Functional Analysis and Applications in Various Diseases.

Canine mesenchymal stromal cells (MSCs) possess the capacity to differentiate into a variety of cell types and secrete a wide range of bioactive molecules in the form of soluble and membrane-bound exosomes. Extracellular vesicles/exosomes are nano-sized vesicles that carry proteins, lipids, and nucleic acids and can modulate recipient cell response in various ways. The process of exosome formation is a physiological interaction between cells. With a significant increase in basic research over the last two decades, there has been a tremendous expansion in research in MSC exosomes and their potential applications in canine disease models. The characterization of exosomes has demonstrated considerable variations in terms of source, culture conditions of MSCs, and the inclusion of fetal bovine serum or platelet lysate in the cell cultures. Furthermore, the amalgamation of exosomes with various nano-materials has become a novel approach to the fabrication of nano-exosomes. The fabrication of exosomes necessitates the elimination of extrinsic proteins, thus enhancing their potential therapeutic uses in a variety of disease models, including spinal cord injury, osteoarthritis, and inflammatory bowel disease. This review summarizes current knowledge on the characteristics, biological functions, and clinical relevance of canine MSC exosomes and their potential use in human and canine research. As discussed, exosomes have the ability to control lethal vertebrate diseases by administration directly at the injury site or through specific drug delivery mechanisms.

Enhancement of Physical Appearance, Skin Permeation, and Odor Reduction Using Liposome of Hydrolyzed Salmon Collagen for Cosmetic Products.

Hydrolyzed collagen (HC) derived from salmon (Oncorhynchus nerka) skin possesses properties that can nourish the skin, and it is one of the active ingredients used in cosmeceutical products for moisturizing the facial skin. However, HC solution gives off a fishy odor and it is gray in color that makes the product unacceptable for cosmetic purposes. This study aimed to use liposome-encapsulated hydrolyzed salmon collagen to improve its physical appearance, skin permeation, and eliminate the fishy odor. Two percent of HC and vitamin B3 (VitB3) were used as active ingredients to incorporate into liposomes. Phosphatidylcholine, cholesterol, and Tween 80 at a suitable weight ratio of 8 : 2 : 1 produced nano-sized vesicles (170.6 ± 0.70 nm) with the highest percentage of entrapment efficiency (95.72 ± 2.00%) of VitB3 and (49.63 ± 1.74%) of HC. Skin permeation and odor detection of the HC-VitB3 liposome were studied using Franz's diffusion cell and gas chromatography, respectively, and compared with HC-VitB3 solution. Subsequently, facial serums were formulated using HC-VitB3 liposomes and HC-VitB3 solutions, and a product satisfaction test was conducted with 100 volunteers to determine their preferred product. The results of the studies of HC-VitB3 liposome serum showed improved formulation appearance, enhanced skin permeation, and better odor elimination compared to the HC-VitB3 serum. Furthermore, seventy-three volunteers in the product satisfaction test preferred and selected the liposomal serum for its superior scent. From all the experimental results, it could be seen that liposomes can help increase skin penetration, and undesirable odors and colors can be masked by the appropriate lipid bilayer structure of liposomes.

Pegylated-liposomes increase the efficacy of Idelalisib in lymphoma B-cells

New drugs and technologies are continuously developed to improve the efficacy and minimize the critical side effects of cancer treatments. The present investigation focuses on the development of a liposomal formulation for Idelalisib, a small-molecule kinase inhibitor approved for the treatment of lymphoid malignancies. Idelalisib is a potent and selective antitumor agent, but it is not indicated nor recommended for first-line treatment due to fatal and serious toxicities. Herein, liposomes are proposed as a delivery tool to improve the therapeutic profile of Idelalisib. Specifically, PEGylated liposomes were prepared, and their physicochemical and technological features were investigated. Light-scattering spectroscopy and cryo-transmission electron microscopy revealed nanosized unilamellar vesicles, which were proved to be stable in storage and in simulated biological fluids.The cytotoxicity of the liposome formulation was investigated in a human non-Hodgkin's lymphoma B cell line. Idelalisib was able to induce death of tumor cells if delivered by the nanocarrier system at increased efficacy. These findings suggest that combining Idelalisib and nanotechnologies may be a powerful strategy to increase the antitumor efficacy of the drug.

Molecular Mechanisms Responsible for the Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Lung Fibrosis.

Mesenchymal stem cell-derived exosomes (MSC-Exos) are nano-sized extracellular vesicles which contain various MSC-sourced anti-fibrotic, immunoregulatory and angio-modulatory proteins (growth factors, immunoregulatory cytokines, chemokines), lipids, and nucleic acids (messenger RNA and microRNAs). Due to their lipid envelope, MSC-Exos easily by-pass all barriers in the body and deliver their cargo directly in target cells, modulating their viability, proliferation, phenotype and function. The results obtained in recently published experimental studies demonstrated beneficial effects of MSC-Exos in the treatment of lung fibrosis. MSC-Exos reduced activation of fibroblasts and prevented their differentiation in myofibroblasts. By delivering MSC-sourced immunoregulatory factors in lung-infiltrated monocytes and T cells, MSC-Exos modulate their function, alleviating on-going inflammation and fibrosis. MSC-Exos may also serve as vehicles for the target delivery of anti-fibrotic and immunomodulatory agents, enabling enhanced attenuation of lung fibrosis. Although numerous pre-clinical studies have demonstrated the therapeutic potential of MSC-Exos in the treatment of pulmonary fibrosis, there are several challenges that currently hinder their clinical implementation. Therefore, in this review article, we summarized current knowledge and we discussed future perspectives regarding molecular and cellular mechanisms which were responsible for the anti-fibrotic, anti-inflammatory and immunoregulatory properties of MSC-Exos, paving the way for their clinical use in the treatment of lung fibrosis.

Rapid isolation of extracellular vesicles using covalent organic frameworks combined with microfluidic technique

Extracellular vesicles (EVs) are nano-sized lipid-membrane vesicles involved in intercellular communication and reflecting the physiological and pathological processes of their parental cells. Rapid isolation of EVs with low cost is an essential precondition for downstream function exploration and clinical applications. In this work, we designed a novel EVs isolation device based on the boronated organic framework (BOF) coated recyclable microfluidic chip (named EVs-BD) to separate EVs from cell culture media. Using a reactive oxygen species responsive phenylboronic ester compound, the highly porous BOF with a pore size in the range of 10–300 nm was prepared by crosslinking γ-cyclodextrin metal-organic frameworks. A mussel-inspired polydopamine (PDA)/polyethyleneimine (PEI) coating was employed to pattern BOF on the PDMS substrate of microfluidic channels. The EVs-BD was demonstrated to offer distinct advantages over the traditional ultracentrifugation method, such as operation simplicity and safety, reduced time and expense, and low expertize requirements. All things considered, a novel approach of EV acquisition has been successfully developed, which can be customized easily to meet the requirements of various EV-relevant research.

Daptomycin Liposomes Exhibit Enhanced Activity against Staphylococci Biofilms Compared to Free Drug.

The purpose of the present study was to investigate the anti-staphylococcal activity of liposomal daptomycin against four biofilm-producing S. aureus and S. epidermidis clinical strains, three of which are methicillin-resistant. Neutral and negatively charged daptomycin-loaded liposomes were prepared using three methods, namely, thin-film hydration (TFH), a dehydration-rehydration vesicle (DRV) method, and microfluidic mixing (MM); moreover, they were characterized for drug encapsulation (EE%), size distribution, zeta-potential, vesicle stability, drug release, and drug integrity. Interestingly, whilst drug loading in THF and DRV nanosized (by extrusion) vesicles was around 30-35, very low loading (~4%) was possible in MM vesicles, requiring further explanatory investigations. Liposomal encapsulation protected daptomycin from degradation and preserved its bioactivity. Biofilm mass (crystal violet, CV), biofilm viability (MTT), and growth curve (GC) assays evaluated the antimicrobial activity of neutral and negatively charged daptomycin-liposomes towards planktonic bacteria and biofilms. Neutral liposomes exhibited dramatically enhanced inhibition of bacterial growth (compared to the free drug) for all species studied, while negatively charged liposomes were totally inactive. Biofilm prevention and treatment studies revealed high antibiofilm activity of liposomal daptomycin. Neutral liposomes were more active for prevention and negative charge ones for treating established biofilms. Planktonic bacteria as well as the matured biofilms of low daptomycin-susceptible, methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) strains were almost completely eradicated by liposomal-daptomycin, indicating the need for their further exploration as antimicrobial therapeutics.

Engineered Hybrid Vesicles and Cellular Internalization in Mammary Cancer Cells.

Extracellular vesicles play an important role in intercellular communication, with the potential to serve as biomaterials for nanocarriers. Combining such extracellular vesicles and liposomes results in advanced drug delivery carriers. In this study, we attempted to fabricate hybrid vesicles using a membrane fusion method and incorporated an anticancer drug. As a result, we successfully prepared nanosized uniform hybrid vesicles and evaluated their physicochemical characteristics and intracellular uptake mechanisms via endocytosis in various cell lines. Compared to liposomes, the hybrid vesicles showed better physical properties and a relatively higher reduction in cell viability, which was presumably dependent on the specific cell type. These findings suggest that fusion-based hybrid vesicles offer a novel strategy for delivering therapeutic agents and provide insights into the types of extracellular vesicles that are useful in fabricating hybrid vesicles to develop an advanced drug delivery system.

Abstract 540: Identification of therapy resistance mediating extracellular vesicles in single-cell level via a novel microfluidic co-culture device development

Abstract Once cancer has metastasized, it is incurable because tumors evolve resistance to all systemically administered anti-cancer therapies. Resistance to therapy has classically been attributed to the presence of a cancer stem cell or genetic tumor cell heterogeneity. Extracellular vesicles (EVs) are nano-sized (40-1000 nm) vesicles that are released by all cells into the extracellular space. EVs carry diverse cargo dependent on the cell of origin and have been studied as a source of novel cancer-specific liquid biopsy biomarkers and contributors to tumor progression and metastasis. However, the paracrine function of EVs in promoting therapy resistance is under-studied, and the impact of EVs released from therapy-resistant cancer cells on surrounding therapy-sensitive cancer cells is unknown. In this study, we develop an innovative microfluidic device, TREVCo, to enable simultaneous single-cell trap, EV detection, and co-culture modules to evaluate EVs-mediated transfer of cellular information between therapy-resistant cancer cells and adjacent cells, and to characterize EVs released from resistant cells and determine their impact on the resistance phenotype of adjacent therapy-sensitive cancer cells. We utilize resistant cells from multiple prostate (PCa) cell lines that have been selected for therapy resistance by culture with increasing dosages of cancer drugs such as cisplatin, docetaxel. We use the matched untreated therapy-sensitive parental cell lines as the sensitive cells. We hypothesize a novel model of therapy resistance in lethal PCa: EVs released from resistant cells contain pro-resistance factors that are transferred to adjacent sensitive cells upon EV uptake, thus directly enabling therapeutic resistance. We will assess the impact of resistant cell-EVs at a single cell level via a novel device, TREVCo, that enables comprehensive downstream analysis. This single-cell approach enables dissection of critical EV-associated therapy-resistant factors within the large heterogeneity of resistant PCa. Co-culture of a single resistant cell and a hundred adjacent sensitive cells mimicking intra-tumoral interactions is also critical to demonstrate evidence of resistant cell secreting factors inducing a pro-resistance phenotype. These studies will be the first-in-field to assess the impact of resistant PCa cell-derived EVs at single-cell resolution. An understanding of resistant cell-derived EVs and the impact of that EV cargo on adjacent sensitive cells will provide critical insight into the acquisition of therapy resistance in lethal PCa. The novel approach to apply resistant cell-derived EVs in co-culture assay with sensitive cells will enable the screening of transmittable resistance-associated factors and provides critical opportunities for accelerating precision medicine for advanced PCa patients. Citation Format: Chi-Ju Kim, Sarah Amend, Kenneth Pienta. Identification of therapy resistance mediating extracellular vesicles in single-cell level via a novel microfluidic co-culture device development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 540.

Exosomes in tumor-stroma crosstalk: Shaping the immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) is a multifaceted disease characterized by a complex interaction between tumor cells and the surrounding microenvironment. Within this intricate landscape, exosomes have emerged as pivotal players in the tumor-stroma crosstalk, influencing the immune microenvironment of CRC. These nano-sized vesicles, secreted by both tumoral and stromal cells, serve as molecular transporters, delivering a heterogeneous mix of biomolecules such as RNAs, proteins, and lipids. In the CRC context, exosomes exert dual roles: they promote tumor growth, metastasis, and immune escape by altering immune cell functions and activating oncogenic signaling pathways and offer potential as biomarkers for early CRC detection and treatment targets. This review delves into the multifunctional roles of exosomes in the CRC immune microenvironment, highlighting their potential implications for future therapeutic strategies and clinical outcomes.

NIR-II Conjugated Electrolytes as Biomimetics of Lipid Bilayers for In Vivo Liposome Tracking.

Liposomes serve as promising and versatile vehicles for drug delivery. Tracking these nanosized vesicles, particularly in vivo, is crucial for understanding their pharmacokinetics. This study introduces the design and synthesis of three new conjugated electrolyte (CE) molecules, which emit in the second near-infrared window (NIR-II), facilitating deeper tissue penetration. Additionally, these CEs, acting as biomimetics of lipid bilayers, demonstrate superior compatibility with lipid membranes compared to commonly used carbocyanine dyes like DiR. To counteract the aggregation-caused quenching effect, CEs employ a twisted backbone, as such their fluorescence intensities can effectively enhance after a fluorophore multimerization strategy. Notably, a "passive" method was employed to integrate CEs into liposomes during the liposome formation, and membrane incorporation efficiency was significantly promoted to nearly 100%. To validate the in vivo tracking capability, the CE-containing liposomes were functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides, serving as tumor-targeting ligands. Clear fluorescent images visualizing tumor site in living mice were captured by collecting the NIR-II emission. Uniquely, these CEs exhibit additional emission peak in visible region, enabling in vitro subcellular analysis using routine confocal microscopy. These results underscore the potential of CEs as a new-generation of membrane-targeting probes to facilitate the liposome-based medicine research.

NIR‐II Conjugated Electrolytes as Biomimetics of Lipid Bilayers for In Vivo Liposome Tracking

AbstractLiposomes serve as promising and versatile vehicles for drug delivery. Tracking these nanosized vesicles, particularly in vivo, is crucial for understanding their pharmacokinetics. This study introduces the design and synthesis of three new conjugated electrolyte (CE) molecules, which emit in the second near‐infrared window (NIR‐II), facilitating deeper tissue penetration. Additionally, these CEs, acting as biomimetics of lipid bilayers, demonstrate superior compatibility with lipid membranes compared to commonly used carbocyanine dyes like DiR. To counteract the aggregation‐caused quenching effect, CEs employ a twisted backbone, as such their fluorescence intensities can effectively enhance after a fluorophore multimerization strategy. Notably, a “passive” method was employed to integrate CEs into liposomes during the liposome formation, and membrane incorporation efficiency was significantly promoted to nearly 100%. To validate the in vivo tracking capability, the CE‐containing liposomes were functionalized with cyclic arginine‐glycine‐aspartic acid (cRGD) peptides, serving as tumor‐targeting ligands. Clear fluorescent images visualizing tumor site in living mice were captured by collecting the NIR‐II emission. Uniquely, these CEs exhibit additional emission peak in visible region, enabling in vitro subcellular analysis using routine confocal microscopy. These results underscore the potential of CEs as a new‐generation of membrane‐targeting probes to facilitate the liposome‐based medicine research.

Exosomes in Glioma: Unraveling Their Roles in Progression, Diagnosis, and Therapy.

Gliomas, the most prevalent primary malignant brain tumors, present a challenging prognosis even after undergoing surgery, radiation, and chemotherapy. Exosomes, nano-sized extracellular vesicles secreted by various cells, play a pivotal role in glioma progression and contribute to resistance against chemotherapy and radiotherapy by facilitating the transportation of biological molecules and promoting intercellular communication within the tumor microenvironment. Moreover, exosomes exhibit the remarkable ability to traverse the blood-brain barrier, positioning them as potent carriers for therapeutic delivery. These attributes hold promise for enhancing glioma diagnosis, prognosis, and treatment. Recent years have witnessed significant advancements in exosome research within the realm of tumors. In this article, we primarily focus on elucidating the role of exosomes in glioma development, highlighting the latest breakthroughs in therapeutic and diagnostic approaches, and outlining prospective directions for future research.

Convergence of Nanotechnology and Bacteriotherapy for Biomedical Applications.

Bacteria have distinctive properties that make them ideal for biomedical applications. They can self-propel, sense their surroundings, and be externally detected. Using bacteria as medical therapeutic agents or delivery platforms opens new possibilities for advanced diagnosis and therapies. Nano-drug delivery platforms have numerous advantages over traditional ones, such as high loading capacity, controlled drug release, and adaptable functionalities. Combining bacteria and nanotechnologies to create therapeutic agents or delivery platforms has gained increasing attention in recent years and shows promise for improved diagnosis and treatment of diseases. In this review, design principles of integrating nanoparticles with bacteria, bacteria-derived nano-sized vesicles, and their applications and future in advanced diagnosis and therapeutics are summarized.