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.

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.

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.

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 patientderived 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.

traditional treatment modalities in the clinic. [1,2] Macrophages are a significant constituent of innate immune system and have an indispensable impact in activating body's first-line defense against infection and cancer. [3] Effectively activating macrophage-mediated immunity holds great potential in cancer immunotherapy. [4] However, cancer cells are masters of immunomodulation and express "don't eat me" signal CD47 on the cellular surface, protecting them from the phagocytosis via binding to signal regulatory protein alpha (SIRPα) receptor on macrophages. [5,6] Blockade of CD47-SIRPα signaling pathway has been widely studied and dozens of CD47 antagonists are being actively tested in clinical trials. [7,8] CD47 checkpoint inhibitors have been demonstrated to not only promote macrophages to directly "eat" cancer cells but also trigger potent T-cell immune responses. [9] Although promising, systemic infusion of these CD47 inhibitors can cause significant side effects, such as thrombocytopenia and anemia. [2,10] Meanwhile, similar to other checkpoint inhibitors, the clinical benefit rate and objective response rate of these antagonists need to be further improved. [10] Thus, addressing these concerns are 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.

Zika virus (ZIKV) has emerged as a global health threat due to its unexpected causal link to devastating neurological disorders such as fetal microcephaly; however, to date, no approved vaccine or specific treatment is available for ZIKV infection. Here we develop a biomimetic nanodecoy (ND) that can trap ZIKV, divert ZIKV away from its intended targets, and inhibit ZIKV infection. The ND, which is composed of a gelatin nanoparticle core camouflaged by mosquito medium host cell membranes, effectively adsorbs ZIKV and inhibits ZIKV replication in ZIKV-susceptible cells. Using a mouse model, we demonstrate that NDs significantly attenuate the ZIKV-induced inflammatory responses and degenerative changes and thus improve the survival rate of ZIKV-challenged mice. Moreover, by trapping ZIKV, NDs successfully prevent ZIKV from passing through physiologic barriers into the fetal brain and thereby mitigate ZIKV-induced fetal microcephaly in pregnant mice. We anticipate that this study will provide new insights into the development of safe and effective protection against ZIKV and various other viruses that threaten public health.

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.

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‐P]MN} 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‐P]MNs possess superior characteristics for immune evasion, active cancer targeting, magnetic resonance imaging, and photothermal therapy. Compared with single cell membrane–coated MNs, [CSC‐P]MNs exhibit prolonged circulation times and enhanced targeting abilities. Moreover, the [CSC‐P]MNs 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.