A Guanidinobenzol-Rich Polymer Overcoming Cascade Delivery Barriers for CRISPR-Cas9 Genome Editing.

The efficient cytosolic delivery of the CRISPR-Cas9 machinery remains a challenge for genome editing. Herein, we performed ligand screening and identified a guanidinobenzol-rich polymer to overcome the cascade delivery barriers of CRISPR-Cas9 ribonucleoproteins (RNPs) for genome editing. RNPs were stably loaded into the polymeric nanoparticles (PGBA NPs) by their inherent affinity. The polymer facilitated rapid endosomal escape of RNPs via a dynamic multiple-step cascade process. Importantly, the incorporation of fluorescence in the polymer helps to identify the correlation between cellular uptake and editing efficiency, increasing the efficiency up to 70% from the initial 30% for the enrichment of edited cells. The PGBA NPs efficiently deliver RNPs for in vivo gene editing via both local and systemic injections and dramatically reduce PCSK9 level. These results indicate that PGBA NPs enable the cascade delivery of RNPs for genome editing, showing great promise in broadening the therapeutic potential of the CRISPR-Cas9 technique.

Tea polyphenol-engineered hybrid cellular nanovesicles for cancer immunotherapy and androgen deprivation therapy.

Androgen deprivation therapy (ADT) is a crucial and effective strategy for prostate cancer, while systemic administration may cause profound side effects on normal tissues. More importantly, the ADT can easily lead to resistance by involving the activation of NF-κB signaling pathway and high infiltration of M2 macrophages in tumor microenvironment (TME). Herein, we developed a biomimetic nanotherapeutic platform by deriving cell membrane nanovesicles from cancer cells and probiotics to yield the hybrid cellular nanovesicles (hNVs), loading flutamide (Flu) into the resulting hNVs, and finally modifying the hNVs@Flu with Epigallocatechin-3-gallate (EGCG). In this nanotherapeutic platform, the hNVs significantly improved the accumulation of hNVs@Flu-EGCG in tumor sites and reprogramed immunosuppressive M2 macrophages into antitumorigenic M1 macrophages, the Flu acted on androgen receptors and inhibited tumor proliferation, and the EGCG promoted apoptosis of prostate cancer cells by inhibiting the NF-κB pathway, thus synergistically stimulating the antitumor immunity and reducing the side effects and resistance of ADT. In a prostate cancer mouse model, the hNVs@Flu-EGCG significantly extended the lifespan of mice with tumors and led to an 81.78% reduction in tumor growth compared with the untreated group. Overall, the hNVs@Flu-EGCG are safe, modifiable, and effective, thus offering a promising platform for effective therapeutics of prostate cancer.

Engineered Bio-Based Hydrogels for Cancer Immunotherapy.

Immunotherapy represents a revolutionary paradigm in cancer management, showcasing its potential to impede tumor metastasis and recurrence. Nonetheless, challenges including limited therapeutic efficacy and severe immune-related side effects are frequently encountered, especially in solid tumors. Hydrogels, a class of versatile materials featuring well-hydrated structures widely used in biomedicine, offer a promising platform for encapsulating and releasing small molecule drugs, biomacromolecules, and cells in a controlled manner. Immunomodulatory hydrogels present a unique capability for augmenting immune activation and mitigating systemic toxicity through encapsulation of multiple components and localized administration. Notably, hydrogels based on biopolymers have gained significant interest owing to their biocompatibility, environmental friendliness, and ease of production. This review delves into the recent advances in bio-based hydrogels in cancer immunotherapy and synergistic combinatorial approaches, highlighting their diverse applications. It is anticipated that this review will guide the rational design of hydrogels in the field of cancer immunotherapy, fostering clinical translation and ultimately benefiting patients.

Tumor Microenvironment-Responsive Nanoparticles Amplifying STING Signaling Pathway for Cancer Immunotherapy.

Insufficient activation of the stimulator of interferon genes (STING) signaling pathway and profoundly immunosuppressive microenvironment largely limits the effect of cancer immunotherapy. Herein, tumor microenvironment (TME)-responsive nanoparticles (PMM NPs) are exploited that simultaneously harness STING and Toll-like receptor 4 (TLR4) to augment STING activation via TLR4-mediated nuclear factor-kappa B signaling pathway stimulation, leading to the increased secretion of type I interferons (i.e., 4.0-fold enhancement of IFN-ß) and pro-inflammatory cytokines to promote a specific T cell immune response. Moreover, PMM NPs relieve the immunosuppression of the TME by decreasing the percentage of regulatory T cells, and polarizing M2 macrophages to the M1 type, thus creating an immune-supportive TME to unleash a cascade adaptive immune response. Combined with an anti-PD-1 antibody, synergistic efficacy is achieved in both inflamed colorectal cancer and noninflamed metastatic breast tumor models. Moreover, rechallenging tumor-free animals with homotypic cells induced complete tumor rejection, indicating the generation of systemic antitumor memory. These TME-responsive nanoparticles may open a new avenue to achieve the spatiotemporal orchestration of STING activation, providing a promising clinical candidate for next-generation cancer immunotherapy.

Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates.

Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines. The nanoDEX, made by encapsulating DEX with the iSEND, efficiently promoted the anti-inflammation effect of DEX in an acute pneumonia mouse model and suppressed DEX-induced bone density reduction in an osteoporosis rat model. Relative to an intravenous administration of DEX at 0.1 milligram per kilogram, a 10-fold lower dose of nanoDEX administered by inhalation produced even better effects against lung inflammation and injury in severe acute respiratory syndrome coronavirus 2-challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases.

Biomimetic manganese-based theranostic nanoplatform for cancer multimodal imaging and twofold immunotherapy.

The limited clinical response and serious side effect have been challenging in cancer immunotherapy resulting from immunosuppressive tumor microenvironment (TME) and inferior drug targeting. Herein, an active targeting TME nanoplatform capable of revising the immunosuppressive TME microenvironment is designed. Briefly, gold nanorods (GNRs) are covered with silica dioxide (SiO2) and then coated manganese dioxide (MnO2) to obtain GNRs@SiO2@MnO2 (GSM). Myeloid-derived suppressor cells (MDSCs) membrane is further camouflaged on the surface of GSM to obtain GNRs@SiO2@MnO2@MDSCs (GSMM). In this system, GSMM inherits active targeting TME capacity of MDSCs. The localized surface plasmon resonance of GNRs is developed in near-infrared II window by MnO2 layer coating, realizing NIR-II window photothermal imaging and photoacoustic imaging of GSMM. Based on the release of Mn2+ in acidic TME, GSMM can be also used for magnetic resonance imaging. In cancer cells, Mn2+ catalyzes H2O2 into ·OH for (chemodynamic therapy) CDT leading to activate cGAS-STING, but also directly acts on STING inducing secretion of type I interferons, pro-inflammatory cytokines and chemokines. Additionally, photothermal therapy and CDT-mediated immunogenic cell death of tumor cells can further enhance anti-tumor immunity via exposure of CRT, HMGB1 and ATP. In summary, our nanoplatform realizes multimodal cancer imaging and dual immunotherapy.

Supramolecular engineering of cell membrane vesicles for cancer immunotherapy.

The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles, promoting scientists to search for novel nanocarriers. Although cell membrane-based delivery systems have attracted extensive attention, further functionalizations are urgently desired to augment their theranostic functions. We propose a cell-friendly supramolecular strategy to engineer cell membranes utilizing cyclodextrin-based host-guest molecular recognitions to fix the defects arising from chemical and genetic modifications. In this study, the supramolecular cell membrane vesicles (SCMVs) specifically accumulate in tumors, benefiting from tumor-homing capability and the enhanced permeability and retention effect. SCMVs co-delivering indocyanine green and an indoleamine 2,3-dioxygenase inhibitor effectively ablate tumors combining photodynamic therapy and immunotherapy. Driven by host-guest inclusion complexation, SCMVs successfully encapsulate resiquimod to repolarize tumor-associated macrophages into M1 phenotype, synergizing with immune checkpoint blockade therapy. This supramolecular engineering methodology based on noncovalent interactions presents a generalizable and cell-friendly tactic to develop living cell-originated nanomaterials for precise cancer therapy.

A decoy microrobot that removes SARS-CoV-2 and its variants in wastewater.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can persist in wastewater for several days, has a risk of waterborne-human transmission. The emergence of SARS-CoV-2 variants with increased infection capacity further highlights the need to remove the virus and restrict its spread in wastewater. Here, we report a decoy microrobot created by camouflaging algae with cell membranes displaying angiotensin-converting enzyme 2 (ACE2) for effective elimination of SARS-CoV-2 and its variants. The decoy microrobots show fast self-propulsion (>85 µm/s), allowing for successful "on-the-fly" elimination of SARS-CoV-2 spike proteins and pseudovirus in wastewater. Moreover, relying on the robust binding between ACE2 and SARS-CoV-2 variants, the decoy microrobots exhibit a broad-spectrum elimination of virus with a high efficiency of 95% for the wild-type strain, 92% for the Delta variant, and 93% for the Omicron variant, respectively. Our work presents a simple and safe decoy microrobot aimed toward eliminating viruses and other environmental hazards from wastewater.

Integration and Reanalysis of Four RNA-Seq Datasets Including BALF, Nasopharyngeal Swabs, Lung Biopsy, and Mouse Models Reveals Common Immune Features of COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1ß and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

Microfluidics-Assisted Fluorescence Mapping of DNA Phosphorothioation.

As the key player of a new restriction modification system, DNA phosphorothioate (PT) modification, which swaps oxygen for sulfur on the DNA backbone, protects the bacterial host from foreign DNA invasion. The identification of PT sites helps us understand its physiological defense mechanisms, but accurately quantifying this dynamic modification remains a challenge. Herein, we report a simple quantitative analysis method for optical mapping of PT sites in the single bacterial genome. DNA molecules are fully stretched and immobilized in a microfluidic chip by capillary flow and electrostatic interactions, improving the labeling efficiency by maximizing exposure of PT sites on DNA while avoiding DNA loss and damage. After screening 116 candidates, we identified a bifunctional chemical compound, iodoacetyl-polyethylene glycol-biotin, that can noninvasively and selectively biotinylate PT sites, enabling further labeling with streptavidin fluorescent nanoprobes. With this method, PT sites in PT+ DNA can be easily detected by fluorescence, while almost no detectable ones were found in PT- DNA, achieving real-time visualization of PT sites on a single DNA molecule. Collectively, this facile genome-wide PT site detection method directly characterizes the distribution and frequency of DNA modification, facilitating a better understanding of its modification mechanism that can be potentially extended to label DNAs in different species.

Neutrophil membrane-coated immunomagnetic nanoparticles for efficient isolation and analysis of circulating tumor cells.

The isolation and analysis of scarce circulating tumor cells (CTCs) with immunomagnetic nanoparticles (IMNs) have shown promising outcomes in noninvasive cancer diagnosis. However, the IMNs adsorb nonspecific proteins after entering into biofluids and the formed protein coronas cover surface targeting ligands, limiting the detection efficiency of IMNs. In addition, the interaction between surface targeting ligands and white blood cells (WBCs) significantly limits the purity of CTCs isolated by IMNs. Furthermore, the interfacial collision of nanoparticles and cells has negative effects on the viability of isolated CTCs. All of these limitations synthetically restrict the isolation and analysis of rare CTCs for early diagnosis and precision medicine. Here, we proposed that surface functionalization of IMNs with neutrophil membranes can simultaneously reduce nonspecific protein adsorption, enhance the interaction with CTCs, reduce the distraction from WBCs, and improve the viability of isolated CTCs. In spiked blood samples, our neutrophil membrane-coated IMNs (Neu-IMNs) exhibited a superior separation efficiency from 41.36% to 96.82% and an improved purity from 40.25% to 90.68% when compared to bare IMNs. Additionally, we successfully isolated CTCs in 19 out of total 20 blood samples from breast cancer patients using Neu-IMNs and further confirmed the feasibility of the isolated CTCs for downstream cell sequencing. Our work provides a new perspective on engineered IMNs for efficient isolation and analysis of CTCs, paving the way for early noninvasive diagnosis of cancer.

Genetically Programmable Fusion Cellular Vesicles for Cancer Immunotherapy.

Herein, we report that genetically programmable fusion cellular vesicles (Fus-CVs) displaying high-affinity SIRPα variants and PD-1 can activate potent antitumor immunity through both innate and adaptive immune effectors. Dual-blockade of CD47 and PD-L1 with Fus-CVs significantly increases the phagocytosis of cancer cells by macrophages, promotes antigen presentation, and activates antitumor T-cell immunity. Moreover, the bispecific targeting design of Fus-CVs ensures better targeting on tumor cells, but less on other cells, which reduces systemic side effects and enhances therapeutic efficacies. In malignant melanoma and mammary carcinoma models, we demonstrate that Fus-CVs significantly improve overall survival of model animals by inhibiting post-surgery tumor recurrence and metastasis. The Fus-CVs are suitable for protein display by genetic engineering. These advantages, integrated with other unique properties inherited from source cells, make Fus-CVs an attractive platform for multi-targeting immune checkpoint blockade therapy.

Detecting changes in water level caused by climate, land cover and dam construction in interconnected river-lake systems.

There is a growing recognition of the broader environmental significance of exploring the relative importance of climate change and anthropogenic impacts on hydrologic fluctuations in river-lake systems. In the case of Dongting Lake, the typical river-lake system, we collected the water level from 1990 to 2019, spanning before and after the operation of the Three Gorges Dam (TGD) in 2003. This study was conducted to detect water level fluctuations in Dongting Lake and to quantify the relative influence of climate, land cover and dam construction on water levels. We defined the impact of the dam construction as the three inlets inflow of Yangtze River (In-YR), and four waters inflow of Hunan (In-HN). The Mann-Kendall (M-K) test revealed the trends and change points of water level fluctuations. Structural Equation Model (SEM) was used to detect the direct and indirect effects of these factors on water level and quantify their relative importance. The MIKE21 hydrodynamic model reflected the spatial-temporal variability of water levels under the action of key driver. The results showed that the water level appeared a downward trend during 1990-2019 and the change point appeared in 2003; During 1990-2002, the significant factors were: precipitation (V = 0.469, P = 0.013), evaporation (V = -0.424, P = 0.029), non-agricultural cover (V = -0.334, P = 0.025), and agricultural cover (V = 0.235, P = 0.033); During 2003-2019, the significant factors were: In-YR (V = 0.436, P = 0.007), In-HN (V = 0.431, P = 0.012), and precipitation (V = 0.349, P = 0.045); The In-YR was the key factor affecting the changes of the water level during 1990-2019; Under the influence of In-YR, the most obvious fluctuation of water level was in the flood adjustment period (Jun-Aug) and the impoundment period (Sep-Nov) when the average declined by about 0.50 and 0.67 m, respectively. Our findings provide a new insight into how to better maintain the stability of river-water system water resources under the influence of multiple factors.

Capturing Cytokines with Advanced Materials: A Potential Strategy to Tackle COVID-19 Cytokine Storm.

The COVID-19 pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused great impact on the global economy and people's daily life. In the clinic, most patients with COVID-19 show none or mild symptoms, while approximately 20% of them develop severe pneumonia, multiple organ failure, or septic shock due to infection-induced cytokine release syndrome (the so-called "cytokine storm"). Neutralizing antibodies targeting inflammatory cytokines may potentially curb immunopathology caused by COVID-19; however, the complexity of cytokine interactions and the multiplicity of cytokine targets make attenuating the cytokine storm challenging. Nonspecific in vivo biodistribution and dose-limiting side effects further limit the broad application of those free antibodies. Recent advances in biomaterials and nanotechnology have offered many promising opportunities for infectious and inflammatory diseases. Here, potential mechanisms of COVID-19 cytokine storm are first discussed, and relevant therapeutic strategies and ongoing clinical trials are then reviewed. Furthermore, recent research involving emerging biomaterials for improving antibody-based and broad-spectrum cytokine neutralization is summarized. It is anticipated that this work will provide insights on the development of novel therapeutics toward efficacious management of COVID-19 cytokine storm and other inflammatory diseases.

The influence of hydrological variables, climatic variables and food availability on Anatidae in interconnected river-lake systems, the middle and lower reaches of the Yangtze River floodplain.

Hydrology-climate changes and food availability are expected to be the primary drivers that result in a loss of waterbirds diversity. Non-biological factors are vital to food availability in interconnected river-lake systems, so in addition to identifying the ecological response to drivers, it is also important to analyze and quantify relationships between drivers. In order to explore the impacts of these drivers on the wintering waterbirds, we selected Dongting Lake (DTL) as a study area, which is a typical interconnected river-lake system in the middle and lower reaches of the Yangtze River Floodplain. The Anatidae species, most of which are herbivorous, were chosen as the representative waterfowl. The Pearson correlation coefficient was applied to select variables related to the timing of water recession and food availability, which have significant influences on the Anatidae. Then, the structural equation model (SEM) was carried out to quantify the relationships among the food availability, hydrological variables, and climatic variables. The results showed that unseasonably early or late water recession had a negative impact on the diversity of the Anatidae, and in particular affected population dynamics of the Lesser White-fronted goose Anser erythropus. Significant changes in Anatidae populations in DTL occurred in response to maximum NDVI (r = 0.53, p<0.01) and the interval time of water recession (r = -0.43, p<0.1). Water level, flow, and interval time of water recession explained 71% of maximum NDVI in DTL. In addition, hydraulic interactions between the mainstream and each lake jointly affected the inundation pattern and the vegetation growth stage of the lake after the flood season, thus affecting foraging suitability. Our findings suggest that water compensation should be carried out within an appropriate range of hydraulic gradient to optimize the time of water recession and improve the suitability of the habitat effectively.

Decoy nanoparticles protect against COVID-19 by concurrently adsorbing viruses and inflammatory cytokines.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.

Activating Macrophage-Mediated Cancer Immunotherapy by Genetically Edited Nanoparticles.

Immunomodulation of macrophages against cancer has emerged as an encouraging therapeutic strategy. However, there exist two major challenges in effectively activating macrophages for antitumor immunotherapy. First, ligation of signal regulatory protein alpha (SIRPα) on macrophages to CD47, a "don't eat me" signal on cancer cells, prevents macrophage phagocytosis of cancer cells. Second, colony stimulating factors, secreted by cancer cells, polarize tumor-associated macrophages (TAMs) to a tumorigenic M2 phenotype. Here, it is reported that genetically engineered cell-membrane-coated magnetic nanoparticles (gCM-MNs) can disable both mechanisms. The gCM shell genetically overexpressing SIRPα variants with remarkable affinity efficiently blocks the CD47-SIRPα pathway while the MN core promotes M2 TAM repolarization, synergistically triggering potent macrophage immune responses. Moreover, the gCM shell protects the MNs from immune clearance; and in turn, the MN core delivers the gCMs into tumor tissues under magnetic navigation, effectively promoting their systemic circulation and tumor accumulation. In melanoma and breast cancer models, it is shown that gCM-MNs significantly prolong overall mouse survival by controlling both local tumor growth and distant tumor metastasis. The combination of cell-membrane-coating nanotechnology and genetic editing technique offers a safe and robust strategy in activating the body's immune responses for cancer immunotherapy.

A novel "on-off-on" fluorescence assay for the discriminative detection of Cu(ii) and l-cysteine based on red-emissive Si-CDs and cellular imaging applications.

Copper ions (Cu2+) and l-cysteine (l-Cys) in the human body always play critical roles in various physiological processes, while abnormal Cu2+ and l-Cys concentrations in the biological system lead to many diseases. In this manuscript, Si-doped carbon dots (Si-CDs) with near-infrared fluorescence were designed for the detection of Cu2+ and l-Cys through the fluorescence "on-off-on" mode. The carbon dots exhibited not only excellent optical merits including good stability against photobleaching and high chemical stability, but also superior biological compatibility. Interestingly, due to the abundant amino groups distributed on the surface of Si-CDs, they could bind to copper ions to form cupric amine complexes and then quench the fluorescence of Si-CDs due to an electron transfer process. In addition, upon the addition of l-Cys, the FL intensity of Si-CDs could be effectively recovered accompanied with complexation between Cu2+ and the functional groups in l-Cys, due to which Cu2+ was removed from the surface of Si-CDs. Notably, as far as we know, these are the first red-emitting carbon dots for copper ion and l-Cys assays in water samples and human plasma samples. Furthermore, this strategy was successfully applied to the determination of Cu2+ and l-Cys in living systems, demonstrating great practicability in biomedical applications.

One-step synthesis of green emission carbon dots for selective and sensitive detection of nitrite ions and cellular imaging application.

In recent years, carbon dot (CD)-based fluorescent sensors for selective ions or small biomolecules have drawn great attention. In this work, highly fluorescent CDs (QY = 21%) were prepared from 2,3-diamino pyridine as the precursor through a facile solvothermal process. The CDs showed high stability and a green emission in aqueous, and the optimal emission wavelength of CDs is 508 nm under the excitation wavelength of 438 nm. Interestingly, a CDs-based nanoprobe was developed for a selective and sensitive fluorescence quenching response to NO2 - in water, and the quenching mechanism was investigated in the work. Besides, the recovery rates of NO2 - in the range of 98-103.5% were found to be acceptable, indicating that the proposed CDs could be act as potential candidates for determination of nitrite ions in real samples. Meanwhile, the nanoprobe was also successfully employed in a visualization biosensing platform for determination of NO2 - in living cells due to its eminent biocompatibility.

Biomimetic Immunomagnetic Nanoparticles with Minimal Nonspecific Biomolecule Adsorption for Enhanced Isolation of Circulating Tumor Cells.

Immunomagnetic micro/nanoparticles (IMNs) have been widely used to isolate rare circulating tumor cells (CTCs) from blood samples for early diagnosis of cancers. However, when entering into biofluids, IMNs nonspecifically adsorb biomolecules and the in situ formed biomolecule corona covers IMN surface ligands and weakens the targeting capabilities of IMNs. In this work, we demonstrated that by surface coating of IMNs with red blood cell (RBC)-derived vesicles, the obtained biomimetic particles (RBC-IMNs) basically adsorb no biomolecules and maintain the CTC targeting ability when exposed to plasma. Compared to IMNs, RBC-IMNs exhibited an excellent cell isolation efficiency in spiked blood samples, which was improved to 95.71% from 60.22%. Furthermore, by using RBC-IMNs, we successfully isolated CTCs in 28 out of 30 prostate cancer patient blood samples and further showed the robustness of RBC-IMNs in downstream cell sequencing. The work presented here provides a new insight into developing targeted nanomaterials for biological and medical applications.