Cell Membrane-camouflaged Nanoparticles Research Articles

Greatly isolated heterogeneous circulating tumor cells using hybrid engineered cell membrane-camouflaged magnetic nanoparticles

BackgroundCirculating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation.MethodsTo address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis.ConclusionsThis study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.Graphical abstract

T Cell and Natural Killer Cell Membrane-Camouflaged Nanoparticles for Cancer and Viral Therapies.

Extensive research has been conducted on the application of nanoparticles in the treatment of cancer and infectious diseases. Due to their exceptional characteristics and flexible structure, they are classified as highly efficient drug delivery systems, ensuring both safety and targeted delivery. Nevertheless, nanoparticles still encounter obstacles, such as biological instability, absence of selectivity, recognition as unfamiliar elements, and quick elimination, which restrict their remedial capacity. To surmount these drawbacks, biomimetic nanotechnology has been developed that utilizes T cell and natural killer (NK) cell membrane-encased nanoparticles as sophisticated methods of administering drugs. These nanoparticles can extend the duration of drug circulation and avoid immune system clearance. During the membrane extraction and coating procedure, the surface proteins of immunological cells are transferred to the biomimetic nanoparticles. Such proteins present on the surface of cells confer several benefits to nanoparticles, including prolonged circulation, enhanced targeting, controlled release, specific cellular contact, and reduced in vivo toxicity. This review focuses on biomimetic nanosystems that are derived from the membranes of T cells and NK cells and their comprehensive extraction procedure, manufacture, and applications in cancer treatment and viral infections. Furthermore, potential applications, prospects, and existing challenges in their medical implementation are highlighted.

MRI-guided cell membrane-camouflaged bimetallic coordination nanoplatform for combined tumor phototherapy

Nanotechnology for tumor diagnosis and optical therapy has attracted widespread interest due to its low toxicity and convenience but is severely limited due to uncontrollable tumor targeting. In this work, homologous cancer cell membrane-camouflaged multifunctional hybrid metal coordination nanoparticles (DRu/Gd@CM) were prepared for MRI-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of tumors. Bimetallic coordination nanoparticles are composed of three functional modules: dopamine, Ru(dcbpy)3Cl2 and GdCl3, which are connected through 1,4-Bis[(1H-imidazole-1-yl)methyl]benzene (BIX). Their morphology can be easily controlled by adjusting the ratio of precursors. Optimistically, the intrinsic properties of the precursors, including the photothermal properties of polydopamine (PDA), the magnetic resonance (MR) response of Gd3+, and the singlet oxygen generation of Ru(dcbpy)3Cl2, are well preserved in the hybrid metal nanoparticles. Furthermore, the targeting of homologous cancer cell membranes enables these coordinated nanoparticles to precisely target tumor cells. The MR imaging capabilities and the combination of PDT and PTT were demonstrated in in vitro experiments. In addition, in vivo experiments indicated that the nanoplatform showed excellent tumor accumulation and therapeutic effects on mice with subcutaneous tumors, and could effectively eliminate tumors within 14 days. Therefore, it expanded the new horizon for the preparation of modular nanoplatform and imaging-guided optical therapy of tumors.

Inflammation-Responsive Cell Membrane-Camouflaged Nanoparticles against Liver Fibrosis via Regulating Endoplasmic Reticulum Stress and Oxidative Stress.

Liver fibrosis represents a reversible stage of various chronic liver diseases that progresses to cirrhosis. This condition is characterized by an imbalance between tissue damage and repair, and the production of fibers in the liver exceeds their degradation. Oxidative stress (OS) resulting from tissue injury and endoplasmic reticulum stress (ERS) triggered by the overproduction of proteins are pivotal factors in liver fibrosis. Melatonin demonstrates the capability to neutralize free radicals, shielding cells from oxidative harm. It is also a specific inhibitor of the ERS receptor transcription activating factor 6 (ATF6), indicating its great potential in ameliorating liver fibrosis. However, its limited water solubility and oral bioavailability of under 15% present hurdles in achieving therapeutic blood concentrations for treating liver fibrosis. The PLGA@Melatonin is constructed by loading melatonin with poly (lactic-co-glycolic acid) (PLGA). Platelet membranes (PM) and activated hepatic stellate cell membranes (HSCM) with high expression of the platelet-derived growth factor receptor (PDGFR) are extracted to successfully construct PM@PLGA@Melatonin and HSCM@PLGA@Melatonin, which are subsequently utilized to treat mice with liver fibrosis. The results illustrated the remarkable therapeutic effects of the two nanoparticles on liver fibrosis, along with their excellent targeting and biosafety properties.

Cell Membrane-Camouflaged Nanoparticles Mediated Nucleic Acids Delivery.

Nucleic acids have emerged as promising therapeutic agents for many diseases because of their potential in modulating gene expression. However, the delivery of nucleic acids remains a significant challenge in gene therapy. Although viral vectors have shown high transfection efficiency, concerns regarding teratogenicity or carcinogenicity have been raised. Non-viral vehicles, including cationic polymers, liposomes, and inorganic materials possess advantages in terms of safety, ease of preparation, and low cost. Nevertheless, they also face limitations related to immunogenicity, quick clearance in vivo, and lack of targeting specificity. On the other hand, bioinspired strategies have shown increasing potential in the field of drug delivery, yet there is a lack of comprehensive reviews summarizing the rapid development of bioinspired nanoparticles based on the cell membrane camouflage to construct the nucleic acids vehicles. Herein, we enumerated the current difficulties in nucleic acid delivery with various non-viral vehicles and provided an overview of bioinspired strategies for nucleic acid delivery.

Red blood cell membrane-camouflaged prednisolone acetate-loaded PLGA nanoparticles for kidney-targeted drug delivery

The lack of renal targeting and adverse drug reactions are key issues in the treatment of glomerulonephritis. Here, we present the development of red blood cell membrane-camouflaged nanoparticles (RBC-PA-NPs) as a targeted drug delivery system for delivering prednisolone acetate (PA) to the glomerular mesangium. We successfully coated erythrocyte membranes onto PA-loaded PLGA nanoparticles (PA-NPs), and the resultant RBC-PA-NPs exhibited a well-defined core-shell structure with a favourable particle size of 104.20 ± 0.35 nm and a surface charge of −15.07 ± 2.13 mV. Toxicity was evaluated by cell viability assays using rat glomerular mesangial cells, and the RBC-PA-NPs showed good biocompatibility. RBC-PA-NPs exhibited reduced uptake by RAW 264.7 cells and greater uptake by rat glomerular mesangial cell lines than PA and PA-NPs. Biodistribution studies revealed that RBC-Cy5-NPs displayed the highest fluorescence intensity in renal tissue and effectively accumulated in the kidney, indicating their targeting effect. In summary, RBC-PA-NPs are a potential system for the kidney-targeted delivery of traditional drugs to improve their efficacy.

Cancer cell membrane biomimetic nanosystem for homologous targeted dual-mode imaging and combined therapy

Hypothesis: The use of tumor cell membrane-camouflaged nanoparticles, specifically the multifunctional biomimetic core–shell nanosystem MPCONPs, can enhance the targeting ability and immune escape functionality of traditional chemotherapy, leading to more precise drug delivery and improved treatment outcomes.Experiments: Preparation of MPCONPs: Autologous tumor cell membrane (CM) fragments are collected and used to create a shell for the nanoparticles. A trypsin-sensitive cationic polylysine framework is synthesized and embedded with oxaliplatin (l-OHP) and Ce6-AuNDs (a singlet oxygen generator). The MPCONPs are formed by assembling these components.Findings: MPCONPs, as nanoparticles camouflaged with tumor CM, have enhanced cellular uptake in cancer cells and improved the efficacy of photodynamic therapy (PDT) and chemotherapy (CT). This offers great potential for their use as individualized therapeutic agents for clinical oncology treatment.

Retracted: Red Blood Cell Membrane-Camouflaged Gold Nanoparticles for Treatment of Melanoma.

[This retracts the article DOI: 10.1155/2022/3514984.].

Biomimetic Epigallocatechin Gallate-Cerium Assemblies for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease that is so far incurable with long-term health risks. The high doses and frequent administration for the available RA drug always lead to adverse side effects. Aiming at the obstacles to achieving effective RA treatment, we prepared macrophage cell membrane-camouflaged nanoparticles (M-EC), which were assembled from epigallocatechin gallate (EGCG) and cerium(IV) ions. Due to its geometrical similarity to the active metal sites of a natural antioxidant enzyme, the EC possessed a high scavenge efficiency to various types of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The macrophage cell membrane assisted M-EC in escaping from the immune system, being uptaken by inflammatory cells, and specifically binding IL-1β. After tail vein injection to the collagen-induced arthritis (CIA) mouse model, the M-EC accumulated at inflamed joints and effectively repaired the bone erosion and cartilage damage of rheumatoid arthritis by relieving synovial inflammation and cartilage erosion. It is expected that the M-EC can not only pave a new way for designing metal-phenolic networks with better biological activity but also provide a more biocompatible therapeutic strategy for effective treatment of RA.

Homologous cancer cell membrane-camouflaged nanoparticles target drug delivery and enhance the chemotherapy efficacy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common digestive tract malignancy that seriously threatens human life and health. Early HCC may be treated by intervention, surgery, and internal radiotherapy, while the choice for late HCC is primarily chemotherapy to prolong patient survival. Lenvatinib (LT) is a Food and Drug Administration (FDA)-approved frontline drug for the treatment of advanced liver cancer and has achieved excellent clinical efficacy. However, its poor solubility and severe side effects cannot be ignored. In this study, a bionic nanodrug delivery platform was successfully constructed. The platform consists of a core of Lenvatinib wrapped with a pH-sensitive polymer, namely, poly(β-amino ester)-polyethylene glycol-amine (PAE-PEG-NH2), and a shell formed by a cancer cell membrane (CCM). The prepared nanodrugs have high drug loading capacity, long-term stability, good biocompatibility, and a long retention time. In addition, the targeting effect of tumor cell membranes and the pH-responsive characteristics of the polymer materials enable them to precisely target tumor cells and achieve responsive release in the tumor microenvironment, which makes them suitable for effective drug delivery. In vivo experiments revealed that the nanodrug showed superior tumor accumulation and therapeutic effects in subcutaneous tumor mice model and could effectively eliminate tumors within 21 days. As a result, it opens up a new way to reduce side effects and improve the specific therapeutic effect of first-line clinical medications to treat tumors.

Reshaping hypoxia and silencing CD73 via biomimetic gelatin nanotherapeutics to boost immunotherapy.

The ubiquitous hypoxic microenvironment at the tumor site helps to regulate hypoxic inducible factor (HIF-1α), up-regulate downstream CD73-adenosine (CD73-ADO) pathways, and further result in effector T cell function exhaustion, which is regarded as a crucial adverse factor in the poor clinical efficacy of immune checkpoint blockade therapy (ICB). How to reshape hypoxic microenvironment and silence CD73 remains a huge challenge to improve ICB therapeutic outcomes. In this study, cancer cell membrane-camouflaged gelatin nanoparticles (CSG@B16F10) were designed to co-deliver oxygen-generating agent catalase (CAT) and CD73siRNA, thus enhancing tumor oxygenation and alleviating CD73-ADO pathway-mediated T cell immunosuppression. The fabricated biomimetic nanoparticles could efficiently achieve immune evading and homologous targeting by virtue of the retention of cancer cell membrane protein. Matrix metalloproteinases (MMP)-responsive gelatin nanoparticles were gradually disintegrated to accelerate the release of payloads. Rapidly released CAT was found to relieve tumor hypoxia by generating endogenous oxygen, while CD73siRNA effectively silenced target gene, synergically inhibiting CD73 protein expression and facilitating T-cell-specific immunity. Upon introduction of CSG@B16F10 in melanoma-bearing mice, PD-L1 checkpoint blockade achieved optimal tumor suppression (∼83%). The enhanced immune efficacy was mainly manifested by enhanced cytotoxic T cell (CTL), reduced regulatory T cells (Tregs), and increased anti-tumor cytokine secretion. This work presents a new paradigm for the ideal design of biomimetic nanoplatforms and the synergistic treatment of hypoxia alleviation and CD73 silence, greatly promising for enhancing clinical immune potency of PD-1/PD-L1 immune checkpoint blockade.

Amplifying Dendritic Cell Activation by Bioinspired Nanometal Organic Frameworks for Synergistic Sonoimmunotherapy.

Despite recent advancements of sonodynamic therapy (SDT) in cancer immunotherapy, challenges have yet to be surmounted to further boost its immunotherapeutic efficacy due to the low-level tumor antigens presentation of dendritic cells (DCs). Cell membrane camouflaged-nanoparticles can integrate the neoantigens of the cancer cell membrane with the multifunctionalities of synthetic nanocores. Herein, sono-responsive nanoparticles coated with DC-targeted antibody chimeric cancer cell membrane are investigated for multimodal therapy. The nanometal organic frameworks (MOFs) that respond to ultrasound are loaded successfully inside the vesicles displaying an anti-DEC205 antibody. The anti-DEC205 chimeric vesicles can directly target and activate DCs, promote tumor antigens cross-presentation, and then produce a cascade amplified T-cell immune response. Upon deep tissue-penetrating sonication, AMR-MOF@AuPt generates large amounts of reactive oxygen species that directly kill cancer cells, further initiating an anti-cancer T cell immune response. Such synergistic sono-immunotherapies effectually inhibit tumor growth and induce strong systemic and long-term immune memory against cancer recurrence and distant metastasis. The authors findings provide DCs and tumor cells of a dual active-targeting cell membrane-coated sono-immunotherapeutic nanoplatform for cancer therapy.

Research update on cell membrane camouflaged nanoparticles for cancer therapy.

Cell membrane-camouflaged biomimetic functionalization of nanoparticles has emerged as a promising strategy for cancer theranostics. These cell membranes used for camouflaging are generally isolated from natural or engineered erythrocytes, neutrophils, macrophages, T lymphatic cells, stem cells, and cancer cells. The camouflaging strategy of coating nanoparticles with cell membranes allows for tumor homotypic targeting through self-recognition as source cells, immune evasion, and a prolonged blood circulation time, thereby improving the effective payload delivery and tumor therapy. More so, some engineered cell membranes with functionalized peptides, proteins and moieties on membrane surface can be transferred for therapy in the same time. In this review, we summarize the latest research on various types of cell membrane-camouflaged nanoparticles aimed at anti-cancer therapy, focusing on the biological advantages of different cell membranes, constitutions of nanoparticles, fabrication processes, key findings, potential therapies, and discuss the major challenges and future opportunities.

Platelet-Tumor Cell Hybrid Membrane-Camouflaged Nanoparticles for Enhancing Therapy Efficacy in Glioma.

PurposeCell membrane-camouflaged nanoparticles (NPs) are drawing increasing attention because their surfaces acquire some characteristics of the cell membranes, making them a unique class of biomimetic materials for diverse applications. Modification of cell membrane or combination of different types of membranes can enhance their functionality.MethodsWe prepared platelet and tumor cell membrane camouflaged β-mangostin-loaded NPs, which were synthesized with platelet–C6 hybrid biomimetic coating, poly(lactic-co-glycolic acid), and β-mangostin (β-PCNPs). Then, we evaluated their targeting ability and anticancer activity against glioma in vitro and in vivo.ResultsBiomimetic coating enhanced active drug targeting and immune escape properties of nanocarrier in C6 and THP-1 cells, respectively, which improved their cytotoxicity. β-PCNPs were characterized to study the inherent properties of both source cells. Compared with bare β-NPs, β-PCNPs exhibited high tumor-targeting capability and induced apoptosis of C6 cells in vitro. Similarly, intravenous administration of drug through β-PCNPs resulted in enhanced tumor-targeting and exhibited excellent rate of inhibition of glioma tumor growth in mice. Moreover, the blood circulation time of drug in mice in the β-PCNP group was markedly prolonged and these mice exhibited better outcome than those in the β-NP group.ConclusionThese results provide a new strategy of utilizing PCNPs as carriers for drug delivery, which improves the targeting efficiency and therapeutic efficacy of chemotherapeutic agents for glioma therapy.

Fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage

Unrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide (E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.

Cell Membrane-camouflaged Multi-functional Dendritic Large Pore Mesoporous Silica Nanoparticles for Combined Photothermal Therapy and Radiotherapy of Cancer

Cell Membrane-camouflaged Multi-functional Dendritic Large Pore Mesoporous Silica Nanoparticles for Combined Photothermal Therapy and Radiotherapy of Cancer

Red blood cell membrane-camouflaged nanoparticles loaded with AIEgen and Poly(I : C) for enhanced tumoral photodynamic-immunotherapy.

Red blood cell (RBC)-mimicking nanoparticles (NPs) offer a promising platform for drug delivery because of their prolonged circulation time, reduced immunogenicity and specific targeting ability. Herein, we report the design and preparation of RBC membrane-bound NPs (M@AP), for tumoral photodynamic-immunotherapy. The M@AP is formed by self-assembly of the positively charged aggregation-induced emission luminogen (AIEgen) (named P2-PPh3) and the negatively charged polyinosinic : polycytidylic acid (Poly(I : C)), followed by RBC membrane encapsulation. P2-PPh3 is an AIE-active conjugated polyelectrolyte with additional photosensitizing ability for photodynamic therapy (PDT), while Poly(I : C) serves as an immune-stimulant to stimulate both tumor and immune cells to activate immunity, and thus reduces tumor cell viability. When applied in tumor-bearing mice, the M@AP NPs are enriched in both the tumor region as a result of an enhanced permeability and retention (EPR) effect, and the spleen because of the homing effect of the RBC-mimicking shell. Upon light irradiation, P2-PPh3 promotes strong ROS generation in tumor cells, inducing the release of tumor antigens (TA). The anti-tumor immunity is further enhanced by the presence of Poly(I : C) in M@AP. Thus, this strategy combines the PDT properties of the AIE-active polyelectrolyte and immunotherapy properties of Poly(I : C) to achieve synergistic activation of the immune system for anti-tumor activity, providing a novel strategy for tumor treatment.

Erythrocytes and Nanoparticles: New Therapeutic Systems

Nano-delivery systems represent one of the most studied fields, thanks to the associated improvement in the treatment of human diseases. The functionality of nanostructures is a crucial point, which the effectiveness of nanodrugs depends on. A hybrid approach strategy using synthetic nanoparticles (NPs) and erythrocytes offers an optimal blend of natural and synthetic materials. This, in turn, allows medical practitioners to exploit the combined advantages of erythrocytes and NPs. Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, as well as the long circulation time allowed by specific surface receptors that inhibit immune clearance. In this review, we will discuss several methods—whole erythrocytes as drug carriers, red blood cell membrane-camouflaged nanoparticles and nano-erythrosomes (NERs)—while paying attention to their application and specific preparation methods. The ability to target cells makes erythrocytes excellent drug delivery systems. They can carry a wide range of therapeutic molecules while also acting as bioreactors; thus, they have many applications in therapy and in the diagnosis of many diseases.

Recent advances in cell membrane-camouflaged nanoparticles for inflammation therapy

During inflammation, inflammatory cells are rapidly recruited to sites of infection or injury, where they cross physiological barriers around the infected site and further infiltrate into the tissues. Other cells, such as erythrocytes, endothelial cells and stem cells, also play prominent roles in host defense and tissue repair. In recent years, nanotechnology has been exploited to deliver drugs to sites of inflammation. For example, nanoparticles camouflaged with a cell membrane are a novel drug-delivery platform that can interact with the immune system and that show great potential for treating inflammation. Encapsulating drugs inside plasma membranes derived from various cells involved in inflammatory processes can be effective against inflammation. This review describes the preparation, characterization, and properties of various types of cell membrane-camouflaged biomimetic nanoparticles. It also summarizes preclinical research into their efficacy against inflammation.

Enhanced Isolation of Fetal Nucleated Red Blood Cells by Enythrocyte-Leukocyte Hybrid Membrane-Coated Magnetic Nanoparticles for Noninvasive Pregnant Diagnostics.

Fetal nucleated red blood cells (fNRBCs) in maternal peripheral blood containing the whole genetic information of the fetus may serve for noninvasive pregnant diagnostics (NIPD). However, the fetal cell-based NIPD is seriously limited by the poor purity of the isolated fNRBCs. Recently, the biomimetic cell membrane-camouflaged nanoparticles containing outstanding features have been widely used to detect and isolate rare cells from the peripheral blood samples. In this work, enythrocyte (RBC) and leukocyte (WBC) membranes are fused and coated onto magnet nanoparticles and then modified with anti-CD147 to isolate fNRBCs from the maternal peripheral blood with significant efficiency (∼90%) and purity (∼87%) in simulated spiked blood samples. Further, fNRBCs were isolated and identified from a series of maternal peripheral blood samples coming from pregnant women of 11-13 gestational weeks, and different chromosomal aneuploidies were diagnosed using fNRBCs isolated from maternal blood in early pregnancy. Our strategy may offer additional opportunity to overcome the limitations of current cell-based NIPD platforms.