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Rational: Interstitial brachytherapy (BT) is a promising radiation therapy for cancer; however, the efficacy of BT is limited by tumor radioresistance. Recent advances in materials science and nanotechnology have offered many new opportunities for BT. Methods: In this work, we developed a biomimetic nanotheranostic platform for enhanced BT. Core-shell Au@AuPd nanospheres (CANS) were synthesized and then encapsulated in platelet (PLT)-derived plasma membranes. Results: The resulting PLT/CANS nanoparticles efficiently evaded immune clearance and specifically accumulated in tumor tissues due to the targeting capabilities of the PLT membrane coating. Under endoscopic guidance, a BT needle was manipulated to deliver appropriate radiation doses to orthotopic colon tumors while sparing surrounding organs. Accumulated PLT/CANS enhanced the irradiation dose deposition in tumor tissue while alleviating tumor hypoxia by catalyzing endogenous H2O2 to produce O2. After treatment with PLT/CANS and BT, 100% of mice survived for 30 days. Conclusions: Our work presents a safe, robust, and efficient strategy for enhancing BT outcomes when adapted to treatment of intracavitary and unresectable tumors.

Cancer is a common cause of mortality in the world. For cancer treatment modalities such as chemotherapy, photothermal therapy and immunotherapy, the concentration of therapeutic agents in tumor tissue is the key factor which determines therapeutic efficiency. In view of this, developing targeted drug delivery systems are of great significance in selectively delivering drugs to tumor regions. Various types of nanomaterials have been widely used as drug carriers. However, the low tumor-targeting ability of nanomaterials limits their clinical application. It is difficult for nanomaterials to penetrate the tumor tissue through passive diffusion due to the elevated tumoral interstitial fluid pressure. As a biological carrier, bacteria can specifically colonize and proliferate inside tumors and inhibit tumor growth, making it an ideal candidate as delivery vehicles. In addition, synthetic biology techniques have been applied to enable bacteria to controllably express various functional proteins and achieve targeted delivery of therapeutic agents. Nanobiohybrids constructed by the combination of bacteria and nanomaterials have an abundance of advantages, including tumor targeting ability, genetic modifiability, programmed product synthesis, and multimodal therapy. Nowadays, many different types of bacteria-based nanobiohybrids have been used in multiple targeted tumor therapies. In this review, firstly we summarized the development of nanomaterial-mediated cancer therapy. The mechanism and advantages of the bacteria in tumor therapy are described. Especially, we will focus on introducing different therapeutic strategies of nanobiohybrid systems which combine bacteria with nanomaterials in cancer therapy. It is demonstrated that the bacteria-based nanobiohybrids have the potential to provide a targeted and effective approach for cancer treatment.

Infectious diseases are a leading cause of mortality worldwide, with viruses and bacteria in particular having enormous impacts on global healthcare. One major challenge in combatting such diseases is a lack of effective drugs or specific treatments. In addition, drug resistance to currently available therapeutics and adverse effects caused by long-term overuse are both serious public health issues. A promising treatment strategy is to employ cell-membrane mimics as decoys to trap and to detain the pathogens. In this Perspective, we briefly review the infection mechanisms adopted by different pathogens at the cellular membrane interface and highlight the applications of cell-membrane-mimicking nanodecoys for systemic protection against infectious diseases. We also discuss the implication of nanodecoy-pathogen complexes in the development of vaccines. We anticipate this Perspective will provide new insights on design and development of advanced materials against emerging infectious diseases.

Vaccines hold enormous potential in cancer immunotherapy by stimulating the body's immune response; unfortunately, the clinical response rates of cancer vaccines are less than 30%. Nanovaccines show the potential to enhance the treatment efficacy of conventional vaccines due to their unique properties, such as efficient co-delivery of cocktail to the secondary lymphatic system, high tumor accumulation and penetration, and customizable delivery of antigens and adjuvants. Meanwhile, the non-invasive visualization of vaccines after their delivery can yield information about in vivo distribution and performance, and aid in their subsequent optimization and translational studies. In this review, we summarize the strategies for the spatiotemporal visualization of nanovaccines in lymph nodes, including whole-body in vivo imaging, intravital organ/cell imaging, and ex vivo tissue/cell imaging. The application of imaging modalities in nanovaccine development is discussed. Moreover, strategies to achieve different combinations of imaging modalities are proposed.

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.

Although anti-PD-1 immunotherapy is widely used to treat melanoma, its efficacy still has to be improved. In this work, we present a therapeutic method that combines immunotherapy and starvation therapy to achieve better antitumor efficacy. We designed the CMSN-GOx method, in which mesoporous silica nanoparticles (MSN) are loaded with glucose oxidase (GOx) and then encapsulate the surfaces of cancer cell membranes to realize starvation therapy. By functionalizing the MSN's biomimetic surfaces, we can synthesize nanoparticles that can escape the host immune system and homologous target. These attributes enable the nanoparticles to have improved cancer targeting ability and enrichment in tumor tissues. Our synthetic CMSN-GOx complex can ablate tumors and induce dendritic cell maturity to stimulate an antitumor immune response. We performed an in vivo analysis of these nanoparticles and determined that our combined therapy CMSN-GOx plus PD-1 exhibits a better antitumor therapeutic effect than therapies using CMSN-GOx or PD-1 alone. Additionally, we used the positron emission tomography imaging to measuring the level of glucose metabolism in tumor tissues, for which we investigate the effect with the cancer therapy in vivo.

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., Enabled by recent advances in materials science and nanotechnology, emerging biomaterials hold great potential to provide better solutions for COVID‐19 cytokine storm and other inflammatory diseases. By reviewing the state‐of‐the‐art cytokine neutralization systems and highlighting the promising technology development, this work intends to spark further research and development activity in this critical research area.

The hypoxic tumor microenvironment (TME) and non-specific distribution of sonosensitizers are two major obstacles that limit practical applications of sonodynamic therapy (SDT) in combating tumors. Here we report a hypoxia-responsive nanovesicle (hMVs) as delivery vehicles of a sonosensitizer to enhance the efficacy of SDT via specific payload release and local oxygenation in the tumor. The nanovesicles are composed of densely packed manganese ferrite nanoparticles (MFNs) embedded in hypoxia-responsive amphiphilic polymer membranes. With δ-aminolevulinic acid (ALA) loaded in the hollow cavities, the hMVs could rapidly dissociate into discrete nanoparticles in the hypoxic TME to release the payload and induce the generation of reactive oxygen species (ROS) under ultrasound (US) radiation. Meanwhile, the released MFNs could catalytically generate O2 to overcome the hypoxic TME and thus enhance the efficacy of SDT. After treatment, the dissociated MFNs could be readily excreted from the body via renal clearance to reduce long term toxicity. In vitro and in vivo experiments displayed effective tumor inhibition via hMVs-mediated SDT, indicating the great potential of this unique nanoplatform in effective SDT by generating sufficient ROS in deep-seated hypoxic tumors that are not readily accessible by conventional photodynamic therapy.

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.

Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while anti-inflammatory M2 macrophages such as tumor-associated macrophages (TAMs) promote tumor growth and invasion. Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy. M1 macrophages target cancerous cells and, therefore, can be used as drug carriers for tumor therapy. Herein, the strategies to engineer macrophages for cancer immunotherapy, such as inhibition of macrophage recruitment, depletion of TAMs, reprograming of TAMs, and blocking of the CD47-SIRPα pathway, are discussed. Further, the recent advances in drug delivery using M1 macrophages, macrophage-derived exosomes, and macrophage-membrane-coated nanoparticles are elaborated. Overall, there is still significant room for development in macrophage-mediated immune modulation and macrophage-mediated drug delivery, which will further enhance current tumor therapies against various malignant solid tumors, including drug-resistant tumors and metastatic tumors.

Assays toward single-cell analysis have attracted the attention in biological and biomedical researches to reveal cellular mechanisms as well as heterogeneity. Yet nowadays microfluidic devices for single-cell analysis have several drawbacks: some would cause cell damage due to the hydraulic forces directly acting on cells, while others could not implement biological assays since they could not immobilize cells while manipulating the reagents at the same time. In this work, we presented a two-layer pneumatic valve-based platform to implement cell immobilization and treatment on-chip simultaneously, and cells after treatment could be collected non-destructively for further analysis. Target cells could be encapsulated in sodium alginate droplets which solidified into hydrogel when reacted with Ca2+ . The size of hydrogel beads could be precisely controlled by modulating flow rates of continuous/disperse phases. While regulating fluid resistance between the main channel and passages by the integrated pneumatic valves, on-chip capture and release of hydrogel beads was implemented. As a proof of concept for on-chip single-cell treatments, we showed cellular live/dead staining based on our devices. This method would have potential in single cell manipulation for biochemical cellular assays.

Background: Circulating tumor cells (CTCs) are a burgeoning topic in cancer biomarker discovery research with minimal invasive blood draws. CTCs can be used as potential biomarkers for disease prognosis, early cancer diagnosis and pharmacodynamics. However, the extremely low abundance of CTCs limits their clinical utility because of technical challenges such as the isolation and subsequent detailed molecular and functional characterization of rare CTCs from patient blood samples. Methods: In this study, we present a novel density gradient centrifugation method employing biodegradable gelatin nanoparticles coated on silicon beads for the isolation, release, and downstream analysis of CTCs from colorectal and breast cancer patients. Results: Using clinical patient/spiked samples, we demonstrate that this method has significant CTC-capture efficiency (>80%) and purity (>85%), high CTC release efficiency (94%) and viability (92.5%). We also demonstrate the unparalleled robustness of our method in downstream CTC analyses such as the detection of PIK3CA mutations. Conclusion: The efficiency and versatility of the multifunctional density microbeads approach provides new opportunities for personalized cancer diagnostics and treatments.

Here, we present a platelet-facilitated photothermal tumor therapy (PLT-PTT) strategy, in which PLTs act as carriers for targeted delivery of photothermal agents to tumor tissues and enhance the PTT effect. Gold nanorods (AuNRs) were first loaded into PLTs by electroporation and the resulting AuNR-loaded PLTs (PLT-AuNRs) inherited long blood circulation and cancer targeting characteristics from PLTs and good photothermal property from AuNRs. Using a gene-knockout mouse model, we demonstrate that the administration of PLT-AuNRs and localizing laser irradiation could effectively inhibit the growth of head and neck squamous cell carcinoma (HNSCC). In addition, we found that the PTT treatment augmented PLT-AuNRs targeting to the tumor sites and in turn, improved the PTT effects in a feedback manner, demonstrating the unique self-reinforcing characteristic of PLT-PTT in cancer therapy.

Due to its unique advantages such as monodispersity and high throughput, droplet microfluidics has been widely used to generate diverse droplets/particles that have specific structures. Herein, we implemented Janus droplet parallel arrangements in a flow-focusing microchip through regulating corresponding fluid flow rates. Initially, fluorescence dye and PBS buffer solution kept laminar flow before the flow-focusing orifice and then was sheared into Janus droplets. Droplet diameter and corresponding generation frequency could be effectively manipulated. Subsequently, the generation of different Janus droplet parallel arrangements (e.g. monolayer, double-layer or three-layer arrangement) could be achieved by fluid regulation.

Circulating tumor cells (CTCs) have been believed to hold significant insights for cancer diagnosis and therapy. Here, we developed a simple and effective method to capture and release viable CTCs using core-shell Fe 3 O 4 @MnO 2 nanoparticles. Fe 3 O 4 @MnO 2 nanoparticles bioconjugated with anti-EpCAM antibody have characteristics of specific recognition, magnetic-driven cell isolation and oxalic acid-assisted cell release. The capture and release efficiency of target cancer cells were ∼83% and ∼55%, respectively. And ∼70% of released cells kept good viability, which could facilitate the subsequent cellular analysis.

The recovery of rare single circulating tumor cells (CTCs) from patients has great potential to facilitate the study of cell heterogeneity and cancer metastasis, which may promote the development of individualized cancer immunotherapy. Herein, a versatile single-cell recovery approach that utilizes an acoustic droplet-induced enzyme responsive platform for the capture and on-demand release of single CTCs is proposed. The platform combines a multifunctional enzyme-responsive gelatin nanoparticle (GNP)-decorated substrate (GNP-chip) for specific capture with an acoustic droplet positioning technique to realize on-demand release of single CTCs. The acoustic droplet dispenser is employed to generate oxidized alginate microdroplets containing the MMP-9 enzyme (OA-MMP-9) with controllable size and precise positioning upon the cell-attached GNP-chip, allowing controlled cell-surface biodegradation under enzymatic reactions followed by calcium chloride (CaCl2) solution treatment to form single-cell encapsulated calcium alginate hydrogels. Benefitting from the existence of hydrogels, the released cells could be efficiently recovered by microcapillary. Results demonstrate that the encapsulated cells maintain good cell morphology in the hydrogels, which allow further single-cell nucleic acid analysis. As a proof-of-concept platform, this approach enables reliable and efficient retrieval of single CTCs and holds the potential for versatility in single-cell analysis systems.

Upconversion nanoparticles (UCNPs), with fascinating optical and chemical features, are a promising new generation of fluorescent probes. Although UCNPs have been widely used in diagnosis and therapy, there is an unmet need for a simple and effective surface engineering method that can produce cancer-targeting UCNPs. Here, we show that by coating particles with macrophage membranes, it becomes possible to utilize the adhesion between macrophages and cancer cells for effective cancer targeting. Natural macrophage membranes along with their associated membrane proteins were reconstructed into vesicles and then coated onto synthetic UCNPs. The resulting macrophage membrane-camouflaged particles (MM-UCNPs) exhibited effective cancer targeting capability inherited from the source cells and were further used for enhanced in vivo cancer imaging. Finally, the blood biochemistry, hematology testing and histology analysis results suggested a good in vivo biocompatibility of MM-UCNPs. The combination of synthetic nanoparticles with biomimetic cell membranes embodies a novel design strategy toward developing biocompatible nanoprobes for potential clinical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 521-530, 2017.

In this paper, autofluorescent gelatin nanoparticles were synthesized as matrix metalloproteinase (MMP) responsive probes for cancer cell imaging. A modified two-step desolvation method was employed to generate these nanoparticles whose size was controllable and had stable autofluorescence. As glutaraldehyde was introduced as the crosslinking agent, the generation of Schiff base (CN) and double carbon bond (CC) between glutaraldehyde and gelatin endowed these gelatin nanoparticles distinct autofluorescence. Considering MMPs were usually overexpressed on the surface of cancer cells and they had degradation ability toward gelatin, we utilized these nanoparticles as imaging probes to responsively monitor the MMP metabolism of cancer cells according to the luminance change. As fluorescent probes, these nanoparticles had facile synthesis procedure and good biocompatibility, and provided a smart strategy to monitor cancer cell behaviors. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2854-2860, 2016.

The effort of incorporating therapeutic drugs with imaging agents has been one of the mainstreams of nanomedicine, which holds great promise in cancer treatment in terms of monitoring therapeutic drug activity and evaluating prognostic index. However, it is still technically challenging to develop nanomedicine endowing a spatiotemporally controllable mechanism of drug release and activatable imaging capability. Here, we developed a yolk-shell type of GSH-responsive nanovesicles (NVs) in which therapeutic drug (Doxorubicin, DOX) and magnetic resonance imaging (MRI) contrast agent (ultrasmall paramagnetic iron oxide nanoparticles, USPIO NPs) formed complexes (denoted as USD) and were encapsulated inside the NVs. The formation of USD complexes is mediated by both the electrostatic adsorption between DOX and poly(acrylic acid) (PAA) polymers and the DOX-iron coordination effect on USPIO NPs. The obtained USD NVs showed a unique yolk-shell structure with restrained drug activity and quenched T(1) MRI contrast ability which, on the other hand, can respond to glutathione (GSH) and lead to drug release and T(1) contrast activation in a spatiotemporally concurrent manner. Furthermore, the USD NVs exhibited great potential to kill HCT116 cancer cells in vitro and effectively inhibit the tumor growth in vivo. This study may shed light on the design of sophisticated nanotheranostics in precision nanomedicine.

Nanotechnology possesses the potential to revolutionize the diagnosis and treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy should have long blood circulation times and active cancer targeting. Additionally, they should be harmless and invisible to the immune system. Here, we developed a biomimetic nanoplatform with the above properties for cancer therapy. Macrophage membranes were reconstructed into vesicles and then coated onto magnetic iron oxide nanoparticles (Fe3O4 NPs). Inherited from the Fe3O4 core and the macrophage membrane shell, the resulting Fe3O4@MM NPs exhibited good biocompatibility, immune evasion, cancer targeting and light-to-heat conversion capabilities. Due to the favorable in vitro and in vivo properties, biomimetic Fe3O4@MM NPs were further used for highly effective photothermal therapy of breast cancer in nude mice. Surface modification of synthetic nanomaterials with biomimetic cell membranes exemplifies a novel strategy for designing an ideal nanoplatform for translational medicine.

Upconversion nanoparticles (UCNPs) with superior optical and chemical features have been broadly employed for in vivo cancer imaging. Generally, UCNPs are surface modified with ligands for cancer active targeting. However, nanoparticles in biological fluids are known to form a long-lived "protein corona", which covers the targeting ligands on nanoparticle surface and dramatically reduces the nanoparticle targeting capabilities. Here, for the first time, we demonstrated that by coating UCNPs with red blood cell (RBC) membranes, the resulting cell membrane-capped nanoparticles (RBC-UCNPs) adsorbed virtually no proteins when exposed to human plasma. We further observed in various scenarios that the cancer targeting ability of folic acid (FA)-functionalized nanoparticles (FA-RBC-UCNPs) was rescued by the cell membrane coating. Next, the FA-RBC-UCNPs were successfully utilized for enhanced in vivo tumor imaging. Finally, blood parameters and histology analysis suggested that no significant systematic toxicity was induced by the injection of biomimetic nanoparticles. Our method provides a new angle on the design of targeted nanoparticles for biomedical applications.

Biomimetic cell-membrane-camouflaged particles with desirable features have been widely used for various biomedical applications. However, there are few reports on employing these particles for cancer drug delivery due to the failure of the membrane coatings to be efficiently degraded in the tumor microenvironment which hampers the drug release. In this work, core-shell SiO2 @TiO2 nanoparticles with enhanced photocatalytic activity are used for controlled degradation of surface erythrocyte membrane coatings. The antitumor drug docetaxel is encapsulated into nanocarriers to demonstrate the controlled drug release under ultraviolet irradiation, and the drug-loaded nanoparticles are further used for enhanced cancer cell therapy. Here, a simple but practical method for degradation of cell membrane coatings is presented, and a good feasibility of using cell membrane-coated nanocarriers for controlled drug delivery is demonstrated.

In this work, we developed a shape-controllable nozzle inside a multilayer PDMS microchip. The nozzle was able to control the shape of the fluid channel in three dimensions. All the four walls of the fluid channel were comprised of pneumatic PDMS membrane valves, and their deformation was controlled by air pressure. As both the limitation of the fluid flux and the shape of the fluid channel were adjustable spatially in three dimensions, this valve-based nozzle generated droplets with less response time and in a more effectively controlled manner comparing to conventional droplet devices. It could also function as a microinjector to modulate the compositions of droplets precisely and continuously. In addition, the nozzle was able to form a specific shape to generate core–shell particles.

We report on the feasible fabrication of microfluidic devices for ferroelectric polymers' synthesis in a rapid and stable fashion. Utilizing micro-mixing and flow-focusing in microchannels, poly(vinylidene fluoride-trifluoroethylene) and copper phthalocyanine are uniformly dispersed in one hydrogel particle, which are then demonstrated to immediate and complete on-chip steady polymerization by moderate ultraviolet treatment. The advantage of our droplet-based microfluidic devices is generating versatile particles from simple spheres to disks or rods, and the lengths of particles can be precisely tuned from 30 to 400 μm through adjusting the flow rates of both disperse and oil phases. In addition, this mixed technique allows for the continuous production of dielectric microparticles with controlled dielectric properties between 10 and 160. Such a microfluidic device offers a flexible platform for multiferroic applications.

Non-invasive prenatal diagnostics (NIPD) has been an emerging field for prenatal diagnosis research. Carrying the whole genome coding of the fetus, fetal nucleated red blood cells (FNRBCs) have been pursued as a surrogate biomarker traveling around in maternal blood. Here, by combining a unique microbead-based centrifugal separation and enzymatic release, we demonstrated a novel method for FNRBC isolation from the blood samples. First, the gelatin-coated silica microbeads were modified with FNRBC-specific antibody (anti-CD147) to capture the target cells in the blood samples. Then, the density difference between microbead-bound FNRBCs and normal blood cells enables the purification of FNRBCs via an improved high-density percoll-based separation. The non-invasive release of FNRBCs can then be achieved by enzymatically degrading the gelatin film on the surface of the microbeads, allowing a gentle release of the captured target cells with as high as 84% efficiency and ∼80% purity. We further applied it to isolate fetal cells from maternal peripheral blood. The released cells were analyzed by real-time polymerase chain reaction to verify their fetal origin and fluorescent in situ hybridization to detect fetal chromosome disorders. This straightforward and reliable alternative platform for FNRBC detection may have the potential for realizing facile NIPD.

Isolation and analysis of rare circulating tumor cells (CTCs) is of great interest in cancer diagnosis, prognosis, and treatment efficacy evaluation. Acoustofluidic cell separation becomes an attractive method due to its contactless, noninvasive, simple, and versatile features. However, the indistinctive physical difference between CTCs and normal blood cells limits the purity of CTCs using current acoustic methods. Herein, we demonstrate a size-amplified acoustic separation and release of CTCs with removable microbeads. CTCs selectively bound to size-amplifiers (40 μm-diameter anti-EpCAM/gelatin-coated SiO2 microbeads) have significant physical differences (size and mechanics) compared to normal blood cells, resulting in an amplification of acoustic radiation force approximately a hundredfold over that of bare CTCs or normal blood cells. Therefore, CTCs can be efficiently sorted out with size-amplifiers in a traveling surface acoustic wave microfluidic device and released from size-amplifiers by enzymatic degradation for further purification or downstream analysis. We demonstrate a cell separation from blood samples with a total efficiency (E total) of ~ 77%, purity (P) of ~ 96%, and viability (V) of ~83% after releasing cells from size-amplifiers. Our method substantially improves the emerging application of rare cell purification for translational medicine.

Cancer cell membrane-coated upconversion nanoprobes (CC-UCNPs) with immune escape and homologous targeting capabilities are used for highly specific tumor imaging. The combination of UCNPs with biomimetic cancer cell membranes embodies a novel materials design strategy and presents a compelling class of advanced materials.

Microfluidics-based circulating tumor cell (CTC) isolation is achieved by using gelatin-coated silica microbeads conjugated to CTC-specific antibodies. Bead-binding selectively enlarges target cell size, providing efficient high-purity capture. CTCs captured can be further released non-invasively. This stratagem enables high-performance CTC isolation for subsequent studies.

Nanoparticles possess the potential to revolutionize cancer diagnosis and therapy. The ideal theranostic nanoplatform should own long system circulation and active cancer targeting. Additionally, it should be nontoxic and invisible to the immune system. Here, the authors fabricate an all-in-one nanoplatform possessed with these properties for personalized cancer theranostics. Platelet-derived vesicles (PLT-vesicles) along with their membrane proteins are collected from mice blood and then coated onto Fe3O4 magnetic nanoparticles (MNs). The resulting core–shell PLT-MNs, which inherit the long circulation and cancer targeting capabilities from the PLT membrane shell and the magnetic and optical absorption properties from the MN core, are finally injected back into the donor mice for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Meanwhile, it is found that the PTT treatment impels PLT-MNs targeting to the PTT sites (i.e., tumor sites), and exactly, in turn, the enhanced targeting of PLT-MNs to tumor sites can improve the PTT effects. In addition, since the PLT membrane coating is obtained from the mice and finally injected into the same mice, PLT-MNs exhibit stellar immune compatibility. The work presented here provides a new angle on the design of biomimetic nanoparticles for personalized diagnosis and therapy of various diseases.

Suppression of the reticuloendothelial system (RES) uptake is one of the most challenging tasks in nanomedicine. Coating stratagems using polymers, such as poly(ethylene glycol) (PEG), have led to great success in this respect. Nevertheless, recent observations of immunological response toward these synthetic polymers have triggered a search for better alternatives. In this work, natural red blood cell (RBC) membranes are camouflaged on the surface of Fe3O4 nanoparticles for reducing the RES uptake. In vitro macrophage uptake, in vivo biodistribution and pharmacokinetic studies demonstrate that the RBC membrane is a superior alternative to the current gold standard PEG for nanoparticle 'stealth'. Furthermore, we systematically investigate the in vivo potential toxicity of RBC membrane-coated nanoparticles by blood biochemistry, whole blood panel examination and histology analysis based on animal models. The combination of synthetic nanoparticles and natural cell membranes embodies a novel and biomimetic nanomaterial design strategy and presents a compelling property of functional materials for a broad range of biomedical applications.