Reactive oxygen species produced by photodynamic therapy enhance docosahexaenoic acid lipid peroxidation and induce the death of breast cancer cells.

Breast cancer remains a serious threat to women's physical and emotional health. The combination therapies can overcome the deficiency of single therapy, enhance the therapeutic effects and reduce the side effects at the same time. In this study, we synthesize a novel nanomedicine that enhanced the therapeutic effects of breast cancer treatment by combining photodynamic therapy and chemotherapy. The doxorubicin (DOX) and photosensitizer methyl pyropheophorbide-a (MPPa) are loaded into the nano-drug delivery system as DPSPFA/MPPa/DOX. In response to near-infrared (NIR) laser, the drugs were quickly released to the cancer cells. The MPPa produces reactive oxygen species (ROS) under the action of photodynamics. Unsaturated fatty acids with ROS promotes lipid peroxidation and the combination of chemotherapy and photodynamic therapy. The data shows that the DPSPFA/MPPa/DOX has a spherical shape, good dispersibility and stability, and the particle size is roughly 200 nm. The drug loading capability of DOX is about 13 %. Both of MCF7 cell model in vitro and breast cancer model in vivo, DPSPFA/MPPa/DOX showed an excellent anti-tumor effect of 86.9 % and without any obvious side effects. These findings might offer potential for a new approach for breast cancer treatment.

Advancing Neurological Health: Insights into Aging, Immunity, and Vascular Dynamics.

This editorial provides an overview of recent advancements in the understanding and treatment of neurological disorders, focusing on aging, immunity, and blood flow, as featured in this special issue. The first section explores the importance of identifying biomarkers of aging and aging-related diseases, such as Alzheimer's Disease, highlighting the emerging role of saliva-based biomarkers and the gut-brain axis in disease diagnosis and management. In the subsequent section, the dysregulated immune systems associated with aging are discussed, emphasizing the intricate landscape of the immune system during aging and its bidirectional relationship with neuroinflammation. Additionally, insights into the involvement of Myeloid-Derived Suppressor Cells (MDSCs) in Multiple Sclerosis (MS) pathogenesis are presented. The third section examines the role of microglia in neuroinflammation and various neurological diseases, including age-related macular degeneration (AMD) and Tuberculous Meningitis (TBM). Furthermore, the therapeutic potential of stem cell and extracellular vesicle-based therapies for stroke is explored, along with molecular mechanism of how inflammation regulates cerebral and myocardial ischemia. Finally, the importance of blood flow in maintaining vascular health and its impact on neurological disorders are discussed, highlighting the potential of novel assessment methods for optimizing patient care. Overall, this special issue offers valuable insights into the complex mechanisms underlying neurological disorders and identifies potential avenues for therapeutic intervention.

Hemorrhagic stroke-induced subtype of inflammatory reactive astrocytes disrupts blood-brain barrier.

Astrocytes undergo disease-specific transcriptomic changes upon brain injury. However, phenotypic changes of astrocytes and their functions remain unclear after hemorrhagic stroke. Here we reported hemorrhagic stroke induced a group of inflammatory reactive astrocytes with high expression of Gfap and Vimentin, as well as inflammation-related genes lipocalin-2 (Lcn2), Complement component 3 (C3), and Serpina3n. In addition, we demonstrated that depletion of microglia but not macrophages inhibited the expression of inflammation-related genes in inflammatory reactive astrocytes. RNA sequencing showed that blood-brain barrier (BBB) disruption-related gene matrix metalloproteinase-3 (MMP3) was highly upregulated in inflammatory reactive astrocytes. Pharmacological inhibition of MMP3 in astrocytes or specific deletion of astrocytic MMP3 reduced BBB disruption and improved neurological outcomes of hemorrhagic stroke mice. Our study demonstrated that hemorrhagic stroke induced a group of inflammatory reactive astrocytes that were actively involved in disrupting BBB through MMP3, highlighting a specific group of inflammatory reactive astrocytes as a critical driver for BBB disruption in neurological diseases.

Hippocampal-derived extracellular vesicle synergistically deliver active adenosine hippocampus targeting to promote cognitive recovery after stroke.

Ischemic stroke is a neurological disease that leads to brain damage and severe cognitive impairment. In this study, extracellular vesicles(Ev) derived from mouse hippocampal cells (HT22) were used as carriers, and adenosine (Ad) was encapsulated to construct Ev-Ad to target the damaged hippocampus. The results showed that, Ev-Ad had significant antioxidant effect and inhibited apoptosis. In vivo, Ev-Ad reduced cell death and reversed inflammation in hippocampus of ischemic mice, and improved long-term memory and learning impairment by regulating the expression of the A1 receptor and the A2A receptor in the CA1 region. Thus, the developmental approach based on natural carriers that encapsulating Ad not only successfully restored nerves after ischemic stroke, but also improved cognitive impairment in the later stage of ischemic stroke convalescence. The development and design of therapeutic drugs provides a new concept and method for the treatment of cognitive impairment in the convalescent phase after ischemic stroke.

CCL5 mediated astrocyte-T cell interaction disrupts blood-brain barrier in mice after hemorrhagic stroke.

The crosstalk between reactive astrocytes and infiltrated immune cells plays a critical role in maintaining blood-brain barrier (BBB) integrity. However, how astrocytes interact with immune cells and the effect of their interaction on BBB integrity after hemorrhagic stroke are still unclear. By performing RNA sequencing in astrocytes that were activated by interleukin-1α (IL-1α), tumor necrosis factor α (TNFα), and complement component 1q (C1q) treatment, we found CCL5 was among the top upregulated genes. Immunostaining and western blot results demonstrated that CCL5 was increased in mice brain after hemorrhagic stroke. Flow cytometry showed that knockout of astrocytic CCL5 reduced the infiltration of CD8+ but not CD4+ T and myeloid cells into the brain (p < 0.05). In addition, knockout CCL5 in astrocytes increased tight junction-related proteins ZO-1 and Occludin expression; reduced Evans blue leakage, perforin and granzyme B expression; improved neurobehavioral outcomes in hemorrhagic stroke mice (p < 0.05), while transplantation of CD8+ T cells reversed these protective effects. Moreover, co-culture of CD8+ T cells with bEnd.3 cells induced the apoptosis of bEnd.3 cells, which was rescued by inhibiting perforin. In conclusion, our study suggests that CCL5 mediated crosstalk between astrocytes and CD8+ T cells represents an important therapeutic target for protecting BBB in stroke.

Co-occurrence of toxic metals, bacterial communities and metal resistance genes in coastal sediments from Bohai bay.

Sediment heavy metal contamination poses substantial risks to microbial community composition and functional gene distribution. Bohai Bay (BHB), the second-largest bay in the Bohai Sea, is subject to severe anthropogenic pollution. However, to date, there have been no studies conducted to evaluate the distribution of metal resistance genes (MRGs) and bacterial communities in the coastal sediments of BHB. In this study, we employed high-throughput sequencing based on 16S rRNA genes and real-time quantitative PCR (qPCR) to provide a comprehensive view of toxic metals, MRGs, and bacterial communities in BHB's coastal sediment samples across two seasons. We detected high levels of Cd in the summer samples and As in the autumn samples. The metal content in most autumn samples and all summer samples, based on ecological indices, indicated low ecological risk. Proteobacteria dominated all samples, followed by Desulfobacterota, Bacteroidota and Campilobacterota. Bacterial community variability was higher between autumn sampling sites but more stable in summer. We detected 9 MRG subtypes in all samples, with abundances ranging from 4.58 × 10-1 to 2.25 copies/16S rRNA copies. arsB exhibited the highest relative abundance, followed by acr3, czcA and arrA. The efflux mechanism is a common mechanism for sediment resistance to metal stress in Bohai Bay. Procrustes analysis indicated that bacterial community composition may be a determinant of MRGs composition in BHB sediments. Network analysis suggested that eight classes could be potential hosts for six MRGs. However, this type of correlation requires further validation. To summarize, our study offers preliminary insights into bacterial community and MRG distribution patterns in heavy metal-exposed sediments, laying the groundwork for understanding microbial community adaptations in multi-metal polluted environments and supporting ecological restoration efforts.

Dissolved and particulate heavy metal pollution status in seawater and sedimentary heavy metals of the Bohai Bay.

Heavy metal contamination has been the focus of many studies owing to its potential risk on the health of coastal ecosystems. The Bohai Bay (BHB) is the second largest bay of Bohai Sea and subjected to serious anthropogenic perturbations. The aim of this study was to evaluate the distribution and pollution status of toxic heavy metals in seawater with two fractions (dissolved and suspended particulate phases) and surface sediments of this coastal system. Therefore, several hydrochemical parameters and concentration of seawater metals and sediment metals were measured at two cruises of 2020 summer and autumn. The spatial distribution and potential ecological risks were examined and their inter-element relationships were analyzed to identify potential geochemical processes. By comparing historical data since 1978, we find declining trends in contents of most trace metals in seawater and sediments, suggesting that recent pollution control in BHB have an effect on diminishing metal pollution. Dissolved metals showed no significant dependence on their particulate phase. The seawater posed a moderate to high level of ecological risk. The hydrochemical factors mainly had a greater impact on dissolved metals during summer, whereas they influenced suspended metals more significantly during autumn. These results provide fundamental information to support environmental quality management and ecological protection in coastal systems.

Preparation of injectable porcine skin-derived collagen and its application in delaying skin aging by promoting the adhesion and chemotaxis of skin fibroblasts.

Collagen, as the main component of human skin, plays a vital role in maintaining dermal integrity. Its loss will lead to dermis destruction and collapse, resulting in skin aging. At present, injection of exogenous collagen is an important means to delay skin aging. In this study, high-purity collagen was extracted from porcine skin. Our research revealed that it can effectively promote the adhesion and chemotaxis of HSF cells. It can also reduce the expression of ß-galactosidase, decrease ROS levels, and increase the expression of the collagen precursors, p53 and p16 in HSF cells during senescence. After local injection into the aging skin of rats, it was found that the number of cells and type I collagen fibers in the dermis increased significantly, and the arrangement of these fibers became more uniform and orderly. Moreover, the important thing is that it is biocompatible. To sum up, the porcine skin collagen we extracted is an anti-aging biomaterial with application potential.

Strong variation in sedimental antibiotic resistomes among urban rivers, estuaries and coastal oceans: Evidence from a river-connected coastal water ecosystem in northern China.

Sediment is thought to be a vital reservoir to spread antibiotic resistance genes (ARGs) among various natural environments. However, the spatial distribution patterns of the sedimental antibiotic resistomes around the Bohai Bay region, a river-connected coastal water ecosystem, are still poorly understood. The present study conducted a comprehensive investigation of ARGs among urban rivers (UR), estuaries (ES) and Bohai Bay (BHB) by metagenomic sequencing. Overall, a total of 169 unique ARGs conferring resistance to 15 antimicrobial classes were detected across all sediment samples. The Kruskal-Wallis test showed that the diversity and abundance of ARGs in the UR were all significantly higher than those in the ES and BHB (p < 0.05 and p < 0.01), revealing the distance dilution of the sedimental resistomes from the river to the ocean. Multidrug resistance genes contained most of the ARG subtypes, whereas rifamycin resistance genes were the most abundant ARGs in this region. Our study demonstrated that most antimicrobial resistomes were highly accumulated in urban river sediments, whereas beta-lactamase resistance genes (mainly PNGM-1) dramatically increased away from the estuary to the open ocean. The relative abundance of mobile genetic elements (MGEs) also gradually decreased from rivers to the coastal ocean, whereas the difference in pathogenic bacteria was not significant in the three classifications. Among MGEs, plasmids were recognized as the most important carriers to support the horizontal gene transfer of ARGs within and between species. According to co-occurrence networks, pathogenic Proteobacteria, Actinobacteria, and Bacteroidetes were recognized as potential and important hosts of ARGs. Heavy metals, pH and moisture content were all recognized as the vital environmental factors influencing the distribution of ARGs in sediment samples. Overall, the present study may help to understand the distribution patterns of ARGs at a watershed scale, and help to make effective policies to control the emergence, spread and evolution of different ARG subtypes in different habitats.

Roles of Ependymal Cells in the Physiology and Pathology of the Central Nervous System.

Ependymal cells are indispensable components of the central nervous system (CNS). They originate from neuroepithelial cells of the neural plate and show heterogeneity, with at least three types that are localized in different locations of the CNS. As glial cells in the CNS, accumulating evidence demonstrates that ependymal cells play key roles in mammalian CNS development and normal physiological processes by controlling the production and flow of cerebrospinal fluid (CSF), brain metabolism, and waste clearance. Ependymal cells have been attached to great importance by neuroscientists because of their potential to participate in CNS disease progression. Recent studies have demonstrated that ependymal cells participate in the development and progression of various neurological diseases, such as spinal cord injury and hydrocephalus, raising the possibility that they may serve as a potential therapeutic target for the disease. This review focuses on the function of ependymal cells in the developmental CNS as well as in the CNS after injury and discusses the underlying mechanisms of controlling the functions of ependymal cells.

NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes.

Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK'772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK'772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis.

Transitional traits determine the acclimation characteristics of the coccolithophore Chrysotila dentata to ocean warming and acidification.

Ocean warming and acidification interactively affect the coccolithophore physiology and drives major biogeochemical changes. While numerous studies investigated coccolithophore under short-term conditions, knowledge on how different transitional periods over long-exposure could influence the element, macromolecular and metabolic changes for its acclimation are largely unknown. We cultured the coccolithophore Chrysotila dentata, (culture generations of 1st, 10th, and 20th) under present (low-temperature low-carbon-dioxide [LTLC]) and projected (high-temperature high-carbon-dioxide [HTHC]) ocean conditions. We examined elemental and macromolecular component changes and sequenced a transcriptome. We found that with long-exposure, most physiological responses in HTHC cells decreased when compared with those in LTLC, however, HTHC cell physiology showed constant elevation between each generation. Specifically, compared to 1st generation, the 20th generation HTHC cells showed increases in quota carbon (Qc:29%), nitrogen (QN :101%), and subsequent changes in C:N-ratio (68%). We observed higher lipid accumulation than carbohydrates within HTHC cells under long-exposure, suggesting that lipids were used as an alternative energy source for cellular acclimation. Protein biosynthesis pathways increased their efficiency during long-term HTHC condition, indicating that cells produced more proteins than required to initiate acclimation. Our findings suggest that the coccolithophore resilience increased between the 1st-10th generation to initiate the acclimation process under ocean warming and acidifying conditions.

Pathogenic bacteria significantly increased under oxygen depletion in coastal waters: A continuous observation in the central Bohai Sea.

The spread of pathogenic bacteria in coastal waters endangers the health of the local people and jeopardizes the safety of the marine environment. However, their dynamics during seasonal hypoxia in the Bohai Sea (BHS) have not been studied. Here, pathogenic bacteria were detected from the 16S rRNA gene sequencing database and were used to explore their dynamics and driving factors with the progressively deoxygenating in the BHS. Our results showed that pathogenic bacteria were detected in all samples, accounting for 0.13 to 24.65% of the total number of prokaryotic sequences in each sample. Pathogenic Proteobacteria was dominated in all samples, followed by Firmicutes, Actinobacteria, Tenericutes, and Bacteroidetes, etc. ß-diversity analysis showed that pathogenic bacteria are highly temporally heterogeneous and regulated by environmental factors. According to RDA analysis, these variations may be influenced by salinity, ammonia, DO, phosphate, silicate, and Chl a. Additionally, pathogenic bacteria in surface water and hypoxia zone were found to be significantly separated in August. The vertical distribution of pathogenic bacterial communities is influenced by several variables, including DO and nutrition. It is noteworthy that the hypoxia zones increase the abundance of certain pathogenic genera, especially Vibrio and Arcobacter, and the stability of the pathogenic bacterial community increased from May to August. These phenomena indicate that the central Bohai Sea is threatened by an increasingly serious pathogenic community from May to August. And the developing hypoxia zone in the future may intensify this phenomenon and pose a more serious threat to human health. This study provides new insight into the changes of pathogenic bacteria in aquatic ecosystems and may help to make effective policies to control the spread of pathogenic bacteria.

Utilizing Cell Culture Assisted Anodization to Fabricate Aluminium Oxide with a Gradient Microstep and Nanopore Structure.

Anodic aluminum oxide (AAO) with a gradient microstep and nanopore structure (GMNP) is fabricated by inversely using cell culture to control the reaction areas in the electrochemical anodization, which shows a larger porosity than that of typical planar AAO. The figure of the microstep is influenced by the cell dehydration temperature which controls the cell shrinkage degree. A GMNP AAO with a diameter of 2.5 cm is achieved. Polymer with a gradient microstep and nanonipple structure is fabricated using the GMNP AAO as the template, which denotes that GMNP AAO could become a broad platform for the structural preparation of various materials with advanced functions.

Brain Microenvironment Responsive and Pro-Angiogenic Extracellular Vesicle-Hydrogel for Promoting Neurobehavioral Recovery in Type 2 Diabetic Mice After Stroke.

Stroke patients with diabetes have worse neurological outcomes than non-diabetic stroke patients, and treatments beneficial for non-diabetic stroke patients are not necessarily effective for diabetic stroke patients. While stem cell-derived extracellular vesicles (EVs) show potential for treating stroke, the results remain unsatisfactory due to the lack of approaches for retaining and controlling EVs released into the brain. Herein, a glucose/reactive oxygen species dual-responsive hydrogel showing excellent injectability, biocompatibility, and self-healing capability is introduced as an EVs-loading vehicle and an intelligent EVs sustained releasing system in the brain. These EVs-hydrogels are developed via crosslinking of phenylboronic acid-modified hyaluronic acid and Poly vinyl alcohol, and fusion with neural stem cell-derived EVs. The results show EVs are stably incorporated into the hydrogels and can be controllably released in response to the brain microenvironment after stroke in type 2 diabetic mice. The EVs-hydrogels exert an excellent angiogenic effect, increasing the migration and tube formation of human umbilical vein endothelial cells. In addition, injection of EVs-hydrogels into the ischemic mouse brain enhances EVs retention and facilitates sustained release, promotes angiogenesis, and improves neurobehavioral recovery. These results suggest such a microenvironment responsive and sustained release EVs-hydrogel system offers a safe, and efficient therapy for diabetic stroke.

Water quality shifts the dominant phytoplankton group from diatoms to dinoflagellates in the coastal ecosystem of the Bohai Bay.

In this study, we conducted two cruises in the Bohai Bay (China) focusing on phytoplankton community and relation to water quality. The evaluation revealed that most of the open area was non-eutrophic, whereas the river inlet had severe eutrophication. Phytoplankton populations respond differently to different aquatic environments and are controlled by more than two factors, as revealed by aggregated boosted tree analysis. Notably, a shift in the phytoplankton community structure was observed during the seasonal transition, from the dominance of diatoms to the co-dominance of diatoms-dinoflagellates. However, the relative abundance of dinoflagellates increased by 14 % in autumn, when the harmful algae species Akashiwo sanguinea exclusively predominated; this was primarily linked to the nutrient ratios, temperature, and dissolved oxygen. The eutrophication and organic pollution had direct effects on phytoplankton abundance. Overall, our findings may provide further insights into the impacts of eutrophic environments on phytoplankton community structure in coastal systems.

Dl-3-n-Butylphthalide Reduced Neuroinflammation by Inhibiting Inflammasome in Microglia in Mice after Middle Cerebral Artery Occlusion.

The inflammatory response is one of the key events in cerebral ischemia, causing secondary brain injury and neuronal death. Studies have shown that the NLRP3 inflammasome is a key factor in initiating the inflammatory response and that Dl-3-n-butylphthalide (NBP) can attenuate the inflammatory response and improve neuronal repair during ischemic stroke. However, whether NBP attenuates the inflammatory response via inhibition of NLRP3 remains unclear. A 90 min middle cerebral artery occlusion was induced in 62 2-month-old adult male ICR mice, and NBP was administered by gavage zero, one, or two days after ischemia. Brain infarct volume, neurological deficits, NLRP3, microglia, and neuronal death were examined in sacrificed mice to explore the correction between NBP effects and NLRP3 expression. NBP significantly reduced infarct volume and attenuated neurological deficits after ischemic stroke compared to controls (p < 0.05). Moreover, it inhibited ASC+ microglia activation and NLRP3 and CASP1 expression in ischemic mice. In addition, neuronal apoptosis was reduced in NBP-treated microglia cultures (p < 0.05). Our results indicate that NBP attenuates the inflammatory response in ischemic mouse brains, suggesting that NBP protects against microglia activation via the NLRP3 inflammasome.

Species and functional diversity of marine macrobenthic community and benthic habitat quality assessment in semi-enclosed waters upon recovering from eutrophication, Bohai Bay, China.

This study investigated the structure and function of macrobenthic community in Bohai Bay upon improvement of water quality due to pollution abatement. A total of 166 species were collected in the summer and autumn sampling, with an increase in sensitive species recorded as compared to data from previous studies. While historical variations in species richness indicated signs of improvement in community structure, results of functional diversity indices revealed that the macrobenthic community in Bohai Bay was still in an early stage of recovery. From BIO-ENV analysis, habitat instability may hinder how community responded to water quality improvement. Results of the benthic habitat quality assessment also indicated that the ecological status in most areas of Bohai Bay was classified as good, while a few estuarine regions were categorized in a poor status.

Blocking C3d+/GFAP+ A1 Astrocyte Conversion with Semaglutide Attenuates Blood-Brain Barrier Disruption in Mice after Ischemic Stroke.

Astrocytes play an essential role in the modulation of blood-brain barrier function. Neurological diseases induce the transformation of astrocytes into a neurotoxic A1 phenotype, exacerbating brain injury. However, the effect of A1 astrocytes on the BBB dysfunction after stroke is unknown. Adult male ICR mice (n=97) were subjected to 90-minute transient middle cerebral artery occlusion (tMCAO). Immunohistochemical staining of A1 (C3d) and A2 (S100A10) was performed to characterize phenotypic changes in astrocytes over time after tMCAO. The glucagon-like peptide-1 receptor agonist semaglutide was intraperitoneally injected into mice to inhibit A1 astrocytes. Infarct volume, atrophy volume, neurobehavioral outcomes, and BBB permeability were evaluated. RNA-seq was adopted to explore the potential targets and signaling pathways of A1 astrocyte-induced BBB dysfunction. Astrocytic C3d expression was increased, while expression of S100A10 was decreased in the first two weeks after tMCAO, reflecting a shift in the astrocytic phenotype. Semaglutide treatment reduced the expression of CD16/32 in microglia and C3d in astrocytes after ischemic stroke (p<0.05). Ischemia-induced brain infarct volume, atrophy volume and neuroinflammation were reduced in the semaglutide-treated mice, and neurobehavioral outcomes were improved compared to control mice (p<0.05). We further demonstrated that semaglutide treatment reduced the gap formation of tight junction proteins ZO-1, claudin-5 and occludin, as well as IgG leakage three days following tMCAO (p<0.05). In vitro experiments revealed that A1 astrocyte-conditioned medium disrupted BBB integrity. RNA-seq showed that A1 astrocytes were enriched in inflammatory factors and chemokines and significantly modulated the TNF and chemokine signaling pathways, which are closely related to barrier damage. We concluded that astrocytes undergo a phenotypic shift over time after ischemic stroke. C3d+/GFAP+ astrocytes aggravate BBB disruption, suggesting that inhibiting C3d+/GFAP+ astrocyte formation represents a novel strategy for the treatment of ischemic stroke.

Targeted delivery of fat extract by platelet membrane-cloaked nanocarriers for the treatment of ischemic stroke.

BACKGROUND: Our previous studies suggest that human fat extract (FE) contains a variety of angiogenic factors and may provide an alternative treatment option for stroke. However, the therapeutic effect is largely limited due to its short half-life, and inaccurate targeting. RESULTS: Herein, we leverage the targeting abilities of platelets (PLTs) to the lesion area of stroke and Arg-Gly-Asp (RGD) peptides to the angiogenic blood vessels to develop a biomimetic nanocarrier that capable of delivering FE precisely to treat stroke. The biomimetic nanocarriers are comprised of FE-encapsulated PLGA (poly(lactic-co-glycolic acid)) core enclosed by RGD peptides decorated plasma membrane of PLTs, namely RGD-PLT@PLGA-FE. We found that RGD-PLT@PLGA-FE not only targeted damaged and inflamed blood vessels but also achieved rapid accumulation in the lesion area of ischemic brain. In addition, RGD-PLT@PLGA-FE kept a sustained release behavior of FE at the lesion site, effectively increased its half-life and promoted angiogenesis and neurogenesis with delivering neurotrophic factors including BDNF, GDNF and bFGF to the brain, that ultimately resulted in blood flow increase and neurobehavioral recovery. CONCLUSIONS: In conclusion, our study provides a new strategy to design a biomimetic system for FE delivery and it is a promising modality for stroke therapy.