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 genetically edited nanoparticle is developed to trigger macrophage‐mediated antitumor immunity through a powerful two‐step strategy: blocking the CD47‐SIRPα pathway in the first step followed by repolarizing tumor‐associated macrophages in the second. This work offers a simple, safe, and effective strategy for activating the body's immune responses for cancer immunotherapy.
Cell membrane coating nanotechnology, which endows nanoparticles with unique properties, displays excellent translational potential in cancer diagnosis and therapy. However, the preparation and ...evaluation of these cell membrane‐coated nanoparticles are based on cell lines and cell‐line‐based xenograft mouse models. The feasibility of cell membrane‐camouflaged nanomaterials is tested in a preclinical setting. Head and neck squamous cell carcinoma (HNSCC) patient‐derived tumor cell (PDTC) membranes are coated onto gelatin nanoparticles (GNPs) and the resulting PDTC@GNPs show efficient targeting to homotypic tumor cells and tissues in patient‐derived xenograft (PDX) models. When the donor‐derived cell membrane of PDTC@GNPs matched those of the host cells, significant targeting capability is observed. In contrast, mismatch between the donor and host results in weak targeting. Furthermore, it is demonstrated that autologous separation and administration of cellular membranes and anticancer cisplatin (Pt)‐loaded PDTC@GNPs, respectively, lead to almost complete tumor ablation in a subcutaneous model and effectively inhibit tumor recurrence in a postsurgery model. The work presented here reinforces the translation of these biomimetic nanoparticles for clinical applications and offers a simple, safe, and effective strategy for personalized cancer treatment.
Cancer cell membrane‐coated nanoparticles, which inherit homologous cancer targeting capability from the source cells, are used for personalized cancer treatment in patient‐derived xenograft models. This represents a simple, safe, and effective strategy for personalized cancer treatment.
Biomimetic cell‐membrane‐camouflaged nanoparticles with desirable features have been widely used for various biomedical applications. However, the current research focuses on single cell membrane ...coating and using multiple cell membranes for nanoparticle functionalization is still challenging. In this work, platelet (PLT) and leukocyte (WBC) membranes are fused, PLT–WBC hybrid membranes are coated onto magnetic beads, and then their surface is modified with specific antibodies. The resulting PLT–WBC hybrid membrane‐coated immunomagnetic beads (HM‐IMBs) inherit enhanced cancer cell binding ability from PLTs and reduce homologous WBC interaction from WBCs, and are further used for highly efficient and highly specific isolation of circulating tumor cells (CTCs). By using spiked blood samples, it is found that, compared with commercial IMBs, the cell separation efficiency of HM‐IMBs is improved to 91.77% from 66.68% and the cell purity is improved to 96.98% from 66.53%. Furthermore, by using the HM‐IMBs, highly pure CTCs are successfully identified in 19 out of 20 clinical blood samples collected from breast cancer patients. Finally, the robustness of HM‐IMBs is verified in downstream CTC analysis such as the detection of PIK3CA gene mutations. It is anticipated that this novel hybrid membrane coating strategy will open new possibilities for overcoming the limitations of current theranostic platforms.
Biomimetic platelet–leukocyte hybrid membrane‐coated immunomagnetic beads with enhanced cancer binding and reduced leukocyte interaction are used for ultrahigh‐efficiency and ‐purity isolation of circulating tumor cells from the blood samples of cancer patient. The combination of biomimetic hybrid cell membrane coating and immunomagnetic beads embodies a novel materials design strategy and presents a compelling class of advanced functional materials.
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.
Genetically programmable fusion cellular vesicles (Fus‐CVs) were developed to elicit potent antitumor immunity by concurrently blocking innate immune checkpoint CD47 and adaptive immune checkpoint PD‐L1. The Fus‐CVs represent a simple, safe and robust alternative to fusion proteins for multi‐targeting immune blockade checkpoint (ICB) therapy.
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.
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‐β) 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.
Tumor microenvironment‐responsive nanoparticles are constructed to achieve spatiotemporal orchestration of innate immune stimulation by harnessing STING and TLR4 pathways. MPLA‐mediated activation of nuclear factor kappa B amplifies STING signaling to promote the secretion of IFN‐β and other inflammatory cytokines, relieving the immunosuppression of tumor microenvironment and thus effectively inhibiting primary tumor growth as well as tumor recurrence and metastasis.
This study considers the largest rural province in China, Henan Province, as an example to analyse government policies aimed at ensuring household energy supply and promoting the clean transformation ...of the rural energy structure. In addition, rural household energy consumption modes and the probability that families will purchase energy-consuming products are investigated. The factors that influence household energy consumption decisions and the energy ladder are examined with a logistic regression. The results show that “gas + electricity” has become the prevailing combined cooking energy pattern in the investigated rural area and that 33% of households use this type of cooking energy. Agricultural income has an obvious positive impact on the rural cooking energy ladder; moreover, increasing households’ agricultural income is important for promoting cleaner cooking energy consumption, as the total income level determines whether energy-consuming products are purchased. The process of urbanization could accelerate the upgrading of rural energy consumption because households with more members who work in or near cities have a greater motivation to use modern cooking energy sources. As economic development and income increase, it is important to implement energy transition policies to improve the supply and consumption of clean energy in rural areas.
•Agricultural income has a more significant impact on the cooking energy ladder.•Households with higher total income are more likely to purchase household products.•Energy consumption modes of the rural area are influenced by urbanization and living habits.•The increasing shares of modern energy presents a cleaner energy consumption tendency.
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.
Cell membrane–based nanosystems with desirable characteristics have been studied extensively for many therapeutic applications. However, current research has focused on single cell membrane, and ...multifunctional fused membrane materials from different membrane types are still rare. Herein, a platelet–cancer stem cell (CSC) hybrid membrane‐coated iron oxide magnetic nanoparticle (MN) {CSC‐PMN} is presented for the first time for the enhanced photothermal therapy of head and neck squamous cell carcinoma (HNSCC). Inherited from the original source cells, the platelet membrane shows immune evading ability due to the surface marker comprising a number of “don't eat me” signals, and the CSC membrane has homotypic targeting capabilities due to the specific surface adhesion molecules. The CSC‐PMNs possess superior characteristics for immune evasion, active cancer targeting, magnetic resonance imaging, and photothermal therapy. Compared with single cell membrane–coated MNs, CSC‐PMNs exhibit prolonged circulation times and enhanced targeting abilities. Moreover, the CSC‐PMNs exhibit a superior photothermal ability that provides excellent HNSCC tumor growth inhibition, particularly in an immunocompetent Tgfbr1/Pten conditional double knockout HNSCC mouse model that contains a more complex tumor microenvironment that is similar to the human HNSCC microenvironment. Collectively, this biomimetic multimembrane‐coated nanoplatform may provide enhanced antitumor efficacy in the complex tumor microenvironment.
A natural cancer stem cell‐platelet hybrid mimic membrane is collected from tumor‐bearing mice and further used for magnetic nanoparticle coating. The obtained biomimetic nanoparticles are then injected into the same mice for magnetic resonance imaging and photothermal therapy. The work presents a novel design strategy for personalized cancer theranostics.
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.
Bio‐based hydrogels have emerged as a focal point in the field of cancer immunotherapy. Specifically, the advancements in bio‐based hydrogels hold significant promise to decrease dosing frequency, enhance treatment efficacy, and mitigate toxicity concurrently. This article provides an overview of hydrogel‐mediated cancer immunotherapy, aiming to guide foundational research and achieve clinical benefits eventually.
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