Search

Abstract The binding of viruses to host-entry factor receptors is an essential step for viral infection. Many studies have shown that macrophages can internalize viruses and degrade them in lysosomes for clearance in vivo. Inspired by these natural behaviors and using SARS-CoV-2 as a testbed, we harvest lysosomes from activated macrophages and anchor the protein-receptor ACE2 as bait, thus constructing a lysosomal “TRAP” (lysoTRAP) that selectively captures, internalizes, and eventually degrades SARS-CoV-2. Through experiments with cells, female mice, female hamsters, and human lung organoids, we demonstrate that lysoTRAP effectively clears SARS-CoV-2. Importantly, unlike therapeutic agents targeting SARS-CoV-2 spike protein, lysoTRAP remains effective against nine pseudotyped variants and the authentic Omicron variant, demonstrating its resistance to SARS-CoV-2 mutations. In addition to the protein-receptor ACE2, we also extend lysoTRAP with the saccharide-receptor sialic acid and verify its excellent antiviral effect against H1N1, highlighting the flexibility of our “TRAP” platform in fighting against various viruses.

Abstract The spread of many infectious diseases relies on aerosol transmission to the respiratory tract. Here we design an intranasal mask comprising a positively-charged thermosensitive hydrogel and cell-derived micro-sized vesicles with a specific viral receptor. We show that the positively charged hydrogel intercepts negatively charged viral aerosols, while the viral receptor on vesicles mediates the entrapment of viruses for inactivation. We demonstrate that when displaying matched viral receptors, the intranasal masks protect the nasal cavity and lung of mice from either severe acute respiratory syndrome coronavirus 2 or influenza A virus. With computerized tomography images of human nasal cavity, we further conduct computational fluid dynamics simulation and three-dimensional printing of an anatomically accurate human nasal cavity, which is connected to human lung organoids to generate a human respiratory tract model. Both simulative and experimental results support the suitability of intranasal masks in humans, as the likelihood of viral respiratory infections induced by different variant strains is dramatically reduced.

Abstract Pulmonary lobe segmentation is an important prerequisite for accurately quantifying pulmonary damage in many pulmonary diseases and planning treatment. However, due to the incomplete lobar structures and morphological changes caused by diseases, the lobe segmentation still encounters great challenges. In this study, a Learnable Interpolation and Extrapolation Network (LIE‐Net) is proposed to form complete and consecutive fissure surfaces by learning to extract information of the fissures from existing fissure points and absent points (unsegmented points belonging to fissures) to predict the z coordinate of the absent fissure points. The completed pulmonary fissures are further used for accurate pulmonary lobe segmentation. Specifically, LIE‐Net takes the coordinate information of existing fissure points (their (x, y, z) coordinates) and absent fissure points (their (x, y) coordinates) as two independent inputs, and predicts the z coordinates of absent points. The proposed LIE‐Net makes voxel‐wise predictions based on the spatial structure characteristics of the lung fissure, and is able to provide a consecutive fissure surface in space. According to the evaluation of radiologists, the lobe segmentation performance was remarkably enhanced in approximately 76% of patients in our additional dataset after the application of LIE‐Net, especially for those cases with large‐scale missing fissures.

Abstract The therapeutic efficacy of whole tumor cell vaccines (TCVs) is modest, which has delayed their translation into personalized immunotherapies in the clinic. Here, we develop a TCV platform based on photothermal nanoparticle-loaded tumor cells, which can be rationally applied to diverse tumor types to achieve on-demand boost of anti-tumor immune responses for inhibiting tumor growth. During the fabrication process, mild photothermal heating by near-infrared (NIR) laser irradiation induces the nanoparticle-bearing tumor cells to express heat shock proteins as endogenous adjuvants. After a single vaccination at the back of tumor-bearing mice, non-invasive NIR laser irradiation further induces mild hyperthermia at vaccination site, which promotes the recruitment, activation, and antigen presentation by dendritic cells. Using an indicator we term fluctuation of tumor growth rate, we determine appropriate irradiation regimens (including optimized irradiation intervals and times). This TCV platform enables on-demand NIR manipulation of immune responses, and we demonstrate potent therapeutic efficacy against six murine models that mimick a range of clinical scenarios, including a model based on humanized mice and patient-derived tumor xenografts.

Messenger RNA (mRNA) has emerged as an innovative therapeutic modality, offering promising avenues for the prevention and treatment of a variety of diseases. The tremendous success of mRNA vaccines in effectively combatting coronavirus disease 2019 (COVID-19) evidences the unlimited medical and therapeutic potential of mRNA technology. Overcoming challenges related to mRNA stability, immunogenicity, and precision targeting has been made possible by recent advancements in lipid nanoparticles (LNPs). This review summarizes state-of-the-art LNP-mRNA-based therapeutics, including their structure, material compositions, design guidelines, and screening principles. Additionally, we highlight current preclinical and clinical trends in LNP-mRNA therapeutics in a broad range of treatments in ophthalmological conditions, cancer immunotherapy, gene editing, and rare-disease medicine. Particular attention is given to the translation and evolution of LNP-mRNA vaccines into a broader spectrum of therapeutics. We explore concerns in the aspects of inadequate extrahepatic targeting efficacy, elevated doses, safety concerns, and challenges of large-scale production procedures. This discussion may offer insights and perspectives on near- and long-term clinical development prospects for LNP-mRNA therapeutics.

Abstract Current methods for intracellular protein analysis mostly require the separation of specific organelles or changes to the intracellular environment. However, the functions of proteins are determined by their native microenvironment as they usually form complexes with ions, nucleic acids, and other proteins. Here, we show a method for in situ cross-linking and analysis of mitochondrial proteins in living cells. By using the poly(lactic-co-glycolic acid) (PLGA) nanoparticles functionalized with dimethyldioctadecylammonium bromide (DDAB) to deliver protein cross-linkers into mitochondria, we subsequently analyze the cross-linked proteins using mass spectrometry. With this method, we identify a total of 74 pairs of protein-protein interactions that do not exist in the STRING database. Interestingly, our data on mitochondrial respiratory chain proteins ( ~ 94%) are also consistent with the experimental or predicted structural analysis of these proteins. Thus, we provide a promising technology platform for in situ defining protein analysis in cellular organelles under their native microenvironment.

Abstract Current attempts in vaccine delivery systems concentrate on replicating the natural dissemination of live pathogens, but neglect that pathogens evolve to evade the immune system rather than to provoke it. In the case of enveloped RNA viruses, it is the natural dissemination of nucleocapsid protein (NP, core antigen) and surface antigen that delays NP exposure to immune surveillance. Here, we report a multi-layered aluminum hydroxide-stabilized emulsion (MASE) to dictate the delivery sequence of the antigens. In this manner, the receptor-binding domain (RBD, surface antigen) of the spike protein was trapped inside the nanocavity, while NP was absorbed on the outside of the droplets, enabling the burst release of NP before RBD. Compared with the natural packaging strategy, the inside-out strategy induced potent type I interferon-mediated innate immune responses and triggered an immune-potentiated environment in advance, which subsequently boosted CD40+ DC activations and the engagement of the lymph nodes. In both H1N1 influenza and SARS-CoV-2 vaccines, rMASE significantly increased antigen-specific antibody secretion, memory T cell engagement, and Th1-biased immune response, which diminished viral loads after lethal challenge. By simply reversing the delivery sequence of the surface antigen and core antigen, the inside-out strategy may offer major implications for enhanced vaccinations against the enveloped RNA virus.

Targeting cancer-associated metabolism is evolving as a promising approach for cancer therapy. Here, the authors generate cancer cell-membrane encapsulated nanoparticles to induce cell cycle arrest and cytotoxicity in lactate-high cancer cells, reducing tumourigensis in glioblastoma cell-line and patient-derived models.

Abstract Background Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. Graphical Abstract

Abstract Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with an extremely low survival rate. New and effective approaches for treatment are therefore urgently needed. Here, we successfully developed M1-like macrophage-derived extracellular vesicles (M1EVs) that overcome multiple challenges via guidance from two macrophage-related observations in clinical specimens from GBM patients: enrichment of M2 macrophages in GBM; and origination of a majority of infiltrating macrophage from peripheral blood. To maximize the synergistic effect, we further functionalized the membranes of M1EVs with two hydrophobic agents (the chemical excitation source CPPO (C) and the photosensitizer Ce6 (C)) and loaded the hydrophilic hypoxia-activated prodrug AQ4N (A) into the inner core of the M1EVs. After intravenous injection, the inherent nature of M1-derived extracellular vesicles CCA-M1EVs allowed for blood-brain barrier penetration, and modulated the immunosuppressive tumor microenvironment via M2-to-M1 polarization, which increased hydrogen peroxide (H2O2) levels. Furthermore, the reaction between H2O2 and CPPO produced chemical energy, which could be used for Ce6 activation to generate large amounts of reactive oxygen species to achieve chemiexcited photodynamic therapy (CDT). As this reaction consumed oxygen, the aggravation of tumor hypoxia also led to the conversion of non-toxic AQ4N into toxic AQ4 for chemotherapy. Therefore, CCA-M1EVs achieved synergistic immunomodulation, CDT, and hypoxia-activated chemotherapy in GBM to exert a potent therapeutic effect. Finally, we demonstrated the excellent effect of CCA-M1EVs against GBM in cell-derived xenograft and patient-derived xenograft models, underscoring the strong potential of our highly flexible M1EVs system to support multi-modal therapies for difficult-to-treat GBM.

Combining the ultra-high user throughput of the light fidelity (LiFi) and the ubiquitous coverage of wireless fidelity (WiFi), the hybrid LiFi and WiFi network (HLWNet) demonstrates unparalleled advantages in indoor wireless data transmission. Due to the line-of-sight propagation nature of the optical signal, the handover decision-making problem in HLWNets, however, becomes more critical and challenging than that in previous heterogeneous networks. In this paper, the handover decision-making problem in the HLWNet is regarded as a binary classification problem, and an artificial neural network (ANN)-based handover scheme is proposed. The complete handover scheme consists of two sets of ANNs that use the information about channel quality, user movement, and device orientation as input features to make handover decisions. After being trained with the labeled datasets that are generated with a novel approach, the ANN-based handover scheme is able to achieve over 95% handover accuracy. The proposed scheme is then compared with benchmarks under an indoor simulation scenario. The simulation results show that the proposed approach can significantly increase user throughput by 20.5 – 46.7% and reduce handover rate by around 59.5 – 78.2% as compared with the benchmarks; in the meanwhile, it maintains a great robustness performance against user mobility and channel variation.

The hybrid light fidelity (LiFi) and wireless fidelity (WiFi) network (HLWNet) is considered to be a potential component of the next generation indoor wireless networks. However, due to the susceptible line-of-sight propagation of optical signal and the ultra-dense deployment of LiFi access points, the handover problem in the HLWNet becomes challenging and it is hard to design a handover scheme that adapts to complex indoor working scenarios. In this paper, we propose a novel handover scheme, in which the handover events in HLWNet are classified into three categories and a particular strategy for each category is applied to calculate the optimal dwell time in the handover procedure. The proposed handover scheme is adaptive to different working situations, since the information about multiple attributes, such as channel quality, user velocity, and arrivals data rate, is gathered to make the handover decision and to calculate the dwell value. The simulation results show that, compared to the benchmarks, the proposed method is able to increase the user throughput by around 65%, decrease the handover rate by up to 80%, and reduce the packet delay by up to 57%. In addition, the proposed method significantly improves the robustness performance of user throughput and handover rate under different scenarios.

Targeting damage to mitochondria has become an effective strategy antitumor therapies. Here, the authors report on nanoagents with upconversion nanoparticles as cores and photoacid-loaded MOFs as shells for NIR triggered Fenton reaction, acidification and calcium overload to provide synergistic mitochondrial damage.

Owing to their autonomous movement characteristics, micromotors can perform various tasks that traditional drug‐delivery carriers fail to perform. The development of adaptable, highly efficient, functional micromotors has become the primary research goal in biomedical field. Micromotors modified with polymers can exhibit strong propulsion ability and unique performance in a complex biological environment, facilitating their application to various complex environments. Herein, different micromotor designs based on natural and synthetic polymers are discussed and the role of polymers in the structure and performance of micromotors is focused on. Overall, the polymer‐modified micromotors can facilitate new developments, particularly in biomedical applications, such as drug delivery and biological detection.

Abstract The rational design of drug delivery systems has led to enhanced targeting, increased efficiency, and a reduction of side effects in chemotherapies and vaccines. As most biological reactions took place at the interface, particle‐stabilized emulsion (Pickering emulsion), may offer major implications for the advanced drug loading, delivery, and controlled release. In fact, it is the aggregating particles that determined the multi‐level structure, multi‐valent cellular interactions, and the multi‐functional physiochemical properties in drug delivery. A deeper understanding on the tunable aggregating patterns and properties, as well as the underlying mechanisms, may pave the way for the efficient drug delivery, and also aided the progressing of “Aggregology” beyond molecules to particles, emulsions, and the biomedical applications. Here, the recent development of Pickering emulsions and their applications in drug delivery were thoroughly reviewed. Strategies to control over the physiochemical properties were illustrated based on particle properties, energy input, and the choices of continuous and dispersion phases. In particular, enough emphasis was attached on the structure‐effect relationship between the tunable physiochemical properties and the delivery process, such as the multi‐level structure for effective loading, flexibility and permeability for enhanced delivery, and the stimuli‐responsiveness for the controlled release. By channeling the unique interfacial properties and the enhanced drug delivery efficiency, this work may shed light on the rational design of Pickering emulsions for the efficient drug delivery.

Oxidation modulators regarding antioxidants and reactive oxygen species (ROS) inducers have been used for the treatment of many diseases. However, a systematic review that refers to delivery system for divergent modulation of oxidative level within the biomedical scope is lacking. To provide a comprehensive summarization and analysis, we review pilot designs for delivering the oxidative modulators and the main applications for inflammatory treatment and tumor therapy. On the one hand, the antioxidants based delivery system can be employed to downregulate ROS levels at inflammatory sites to treat inflammatory diseases (e.g., skin repair, bone-related diseases, organ dysfunction, and neurodegenerative diseases). On the other hand, the ROS inducers based delivery system can be employed to upregulate ROS levels at the tumor site to kill tumor cells (e.g., disrupt the endogenous oxidative balance and induce lethal levels of ROS). Besides the current designs of delivery systems for oxidative modulators and the main application cases, prospects for future research are also provided to identify intelligent strategies and inspire new concepts for delivering oxidative modulators.

Abstract Bio–nano interfaces are integral to all applications of nanomaterials in biomedicine. In addition to peptide‐ligand‐functionalized nanomaterials, passivation on 2D nanomaterials has emerged as a new regulatory factor for integrin activation. However, the mechanisms underlying such ligand‐independent processes are poorly understood. Here, using graphene oxide passivated with polyethylene glycol (GO‐PEG) as a test bed, a ternary simulation model is constructed that also includes a membrane and both subunits of integrin αvβ8 to characterize GO‐PEG‐mediated integrin activation on the cell membrane in a ligand‐independent manner. Combined with the experimental findings, production simulations of the ternary model show a three‐phase mechanotransduction process in the vertical interaction mode. Specifically, GO‐PEG first induces lipid aggregation‐mediated integrin proximity, followed by transmembrane domain rotation and separation, leading to the extension and activation of extracellular domains. Thus, this study presents a complete picture of the interaction between passivated 2D nanomaterials and cell membranes to mediate integrin activation, and provides insights into the potential de novo design and rational use of novel desirable nanomaterials at diverse bio–nano interfaces.

Abstract As membrane‐bound extracellular vesicles, exosomes have targeting ability for specific cell types, and the cellular environment strongly impacts their content and uptake efficiency. Inspired by these natural properties, the impacts of various cellular stress conditions on the uptake efficiency of tumor iterated exosomes are evaluated, and low‐pH treatment caused increased uptake efficiency and retained cell‐type specificity is found. Lipidomics analyses and molecular dynamics simulations reveal a glycerolipid self‐aggregation‐based mechanism for the enhanced homologous uptake. Furthermore, these low‐pH reprogrammed exosomes are developed into a smart drug delivery platform, which is capable of specifically targeting tumor cells and selectively releasing diverse chemodrugs in response to the exosome rupture by the near‐infrared irradiance‐triggered burst of reactive oxygen species. This platform exerts safe and enhanced antitumor effects demonstrated by multiple model mice experiments. These results open a new avenue to reprogram exosomes for smart drug delivery and potentially personalized therapy against their homologous tumor.

In order to investigate the effect of heat treatment on the mechanical properties of the Al-7.0Si-0.3Mg alloy at 20–60 °C under different heat treatment processes, the tensile mechanical properties of Al-7.0Si-0.3Mg at low temperature after heat treatment were explored. The microstructure of Al-7.0Si-0.3Mg was observed by scanning electron microscopy (SEM) and transmission electron microscopy. The results show that the resistance of the dislocation movement in α-Al increased in the low-temperature condition, which is beneficial for the number of Si phase fractures that increase to enhance the tensile strength and weaken the elongation of the Al-7.0Si-0.3Mg alloy. After the solution treatment, the particle size of the Si phase reduced, while the morphology became rounded. In the early stage of aging, a GP region is generated inside the α-Al. With the prolonging of aging time, the acicular β″ phase is formed and then grows into rod-shaped β′. In the overaging stage, β′ eventually grows into flaky β. Due to the different linear expansion coefficients of the α-Al and the Mg2Si phase in the Al-7.0Si-0.3Mg alloy, the α-Al is squeezed by the Mg2Si phase under the effect of low-temperature shrinkage.

Abstract Nanovaccines have attracted booming interests in vaccinology studies, but the profound impacts of their delivery mode on immune response remain unrealized. Herein, immunostimulatory CpG‐modified tumor‐derived nanovesicles (CNVs) are used as a nanovaccine testbed to initially evaluate the impacts of three distinct delivery modes, including mono‐pulse CNVs, staggered‐pulse CNVs, and gel‐confined CNVs. Fundamentally, delivery mode has enormous impacts on the immunomodulatory effects, altering the spatiotemporal distribution of nanovaccine residence and dendritic cell–T cell interaction in lymph nodes, and finally affecting subsequent T cell‐mediated immune performance. As a result, the gel‐confined delivery mode offers the best therapeutic performance in multiple tumor models. When extending evaluation to examine how the various delivery modes impact the performance of liposome‐based nanovaccines, similar trends in intralymph node distribution and antitumor effect are observed. This work provides a strong empirical foundation that nanovaccine researchers should position delivery mode near the top of their considerations for the experimental design, which should speed up nanovaccine development and facilitate efficient selection of appropriate delivery modes in the clinic.

The origin of Fc receptor-based phagocytosis is unknown, although plasma lipid redistribution after solid structure binding induces similar phagocytic signaling. Here, Mu et al. show that PIP2 accumulation from plasma membrane deformation recruits Moesin to trigger receptor-independent phagocytosis.

Malaria is a life-threatening global epidemic disease and has caused more than 400,000 deaths in 2019. To control and prevent malaria, the development of a vaccine is a potential method. An effective malaria vaccine should either combine antigens from all stages of the malaria parasite’s life cycle, or epitopes of multiple key antigens due to the complexity of the Plasmodium parasite. Malaria’s random constructed antigen-1 (M.RCAg-1) is one of the recombinant vaccines, which was selected from a DNA library containing thousands of diverse multi-epitope chimeric antigen genes. Moreover, besides selecting an antigen, using an adjuvant is another important procedure for most vaccine development procedures. Freund’s adjuvant is considered an effective vaccine adjuvant for malaria vaccine, but it cannot be used in clinical settings because of its serious side effects. Traditional adjuvants, such as alum adjuvant, are limited by their unsatisfactory immune effects in malaria vaccines, hence there is an urgent need to develop a novel, safe and efficient adjuvant. In recent years, Pickering emulsions have attracted increasing attention as novel adjuvant. In contrast to classical emulsions, Pickering emulsions are stabilized by solid particles instead of surfactant, having pliability and lateral mobility. In this study, we selected aluminum hydroxide gel (termed as “alum”) as a stabilizer to prepare alum-stabilized Pickering emulsions (ALPE) as a malaria vaccine adjuvant. In addition, monophosphoryl lipid A (MPLA) as an immunostimulant was incorporated into the Pickering emulsion (ALMPE) to further enhance the immune response. In vitro tests showed that, compared with alum, ALPE and ALMPE showed higher antigen load rates and could be effectively endocytosed by J774a.1 cells. In vivo studies indicated that ALMPE could induce as high antibody titers as Freund’s adjuvant. The biocompatibility study also proved ALMPE with excellent biocompatibility. These results suggest that ALMPE is a potential adjuvant for a malaria vaccine.

Polyethylene glycol has been widely utilized to functionalize nanomaterials in order to improve their biocompatibility. Here, the authors demonstrate that PEGylated nano-graphene oxide can elicit an inflammatory response, contradicting current literature.

Traditional barley agroecosystem in the Himalaya region harbour a great diversity of hulless barley landraces. This diversity has been considered largely impacted by agro-ecozone factors as documents by former researches. Five case study sites were selected from Northwest Yunnan to represent five agro-ecozones: Tangman (hot and dry valley), Kena (hot and wet valley), Hongpo (alpine region), Napa (marshy wetland), and Xiangka (mild slopes in high plateau). A participatory rural appraisal was carried out to acquire data for 28 cultural, socio-economic, ecological and agricultural factors in these five sites from 2012 to 2014. Multiple correspondence analysis was conducted to evaluate the weight of the selected factors on the diversity of agroecosystems. Results showed that the diversity and percentage of hulless barley in the area was largely differentiated between the zones, and the differences principally originated from 5 factors, including Religious hulless barley use, Weight of fodder using, Chemical fertilizer, Crop varieties, and Seed exchange consumption. Cultural factors were the most influencing factors, followed by agricultural factors, natural factors and the last social factors. In the cultural factors, religious use hulless barley and seed exchange customs were very important. High elevation and farmers’ distance from cities were the most important factors fostering on-farm hulless barley landrace diversity. The conservation of agricultural biodiversity in traditional Tibetan agriculture ecosystem should be emphasized. Keywords: Hulless barley, NW Yunnan, Agro-ecozones

Therapeutic vaccines that arouse the cytotoxic T cell immune response to reject infected cells have been investigated extensively for treating disease. Due to the large amounts of resident antigen-presenting cells (APCs) and T cells in lymph nodes, great efforts have been made to explore the strategy of targeting lymph nodes directly with nanovaccines to activate T cells. However, these nanovaccines still have several problems, such as a low loading efficiency and compromised activity of antigens and adjuvants derived from traditional complicated preparation. There are also safety concerns about materials synthesized without FDA approval. Herein, we construct an assembled nanoparticle composed of an antigen (ovalbumin, OVA) and adjuvant (CpG) to ensure its safety and high loading efficiency. The activity of both components was well preserved due to the mild self-assembly process. The small size, narrow distribution, negative charge, and good stability of the nanoparticle endow these nanovaccines with superior capacity for lymph node targeting. Correspondingly, the accumulation at lymph nodes can be improved by 10-fold. Subsequently, due to the sufficient APC internalization and maturation in lymph nodes, ~60% of T cells are stimulated to proliferate and over 70% of target cells are specifically killed. Based on the effective and quick cellular immune response, the assembled nanoparticles exhibit great potential as therapeutic vaccines.

Abstract Failure in enhancing antigen immunogenicity has limited the development of cancer vaccine. Inspired by effective immune responses toward microorganisms, demi‐bacteria (DB) from Bacillus are engineered as carriers for cancer vaccines. The explored hydrothermal treatment enables the Bacillus to preserve optimal pathogen morphology with intrinsic mannose receptor agonist. Meanwhile, the treated Bacillus can be further endowed with ideal hollow/porous structure for efficient accommodation of antigen and adjuvant, such as CpG. Therefore, this optimal engineered nanoarchitecture allows multiple immunostimulatory elements integrate in a pattern closely resembling that of bacterial pathogens. Such pathogen mimicry greatly enhances antigen uptake and cross‐presentation, resulting in stronger immune activation suitable for cancer vaccines. Indeed, DB‐based biomimetic vaccination in mice induces synergistic cellular and humoral immune responses, achieving potent therapeutic and preventive effects against cancer. Application of microorganism‐sourced materials thus presents new opportunities for potent cancer therapy.

In this study, a polymeric lipid nanoparticle (NP) (simplified as Lipid NP) was reported as a promising oral vaccine delivery system. The Lipid NPs composed of a hydrophobic polymeric poly(d,l-lactide-co-glycolide) (PLGA) core and a surface coating of lipid monolayer. Membrane emulsification technique was used to obtain uniform-sized Lipid NPs. Ovalbumin (OVA) was used as a model vaccine. Compared with the pure PLGA NPs, the Lipid NPs achieved higher loading capacity (LC) and entrapment efficiency (EE) for the encapsulated OVA. An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal (GI) environment for a long time. In addition, a human microfold cell (M-cell) transcytotic assay demonstrated that due to a lipid layer structure on the particle surface, the Lipid NPs showed higher affinity to the M-cells. Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells, the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.