Cell Membrane-coated Nanoparticles Research Articles

Cell membrane-coated nanoparticles for immunotherapy

Nanoparticle-based disease detection, prevention and therapies have gained increased interests in biomedical applications, owing to their significant advantages in therapeutic efficacy and safety. Nonetheless, suffering from the challenges including fast recognition and clearance of foreign nanoparticles by innate immune system before arriving at diseased regions, clinical applications of nanoparticles are usually intercepted. Among various strategies for reducing non-specific phagocytosis and enhancing disease-targeting efficiency of nanoparticles, membrane coating nanotechnology exhibits great potential in the disease diagnosis and therapeutics due to both the structural and functional preservation of membrane proteins from source cells. Benefiting the inherited immune-regulation capacities, this review mainly summarized the latest development of such biomimetic nanoparticles for immunotherapy in treating immune-related diseases including microbial infections, inflammation, tumor and autoimmune diseases. This review mainly summarized the latest development of cell membrane-coated nanoparticles for immunotherapy in treating immune-related diseases including microbial infections, inflammation, tumor and autoimmune diseases.

Nanoparticle approaches against SARS-CoV-2 infection

Coronavirus disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst pandemic disease of the current millennium. To address this crisis, therapeutic nanoparticles, including inorganic nanoparticles, lipid nanoparticles, polymeric nanoparticles, virus-like nanoparticles, and cell membrane-coated nanoparticles, have all offered compelling antiviral strategies. This article reviews these strategies in three categories: (1) nanoparticle-enabled detection of SARS-CoV-2, (2) nanoparticle-based treatment for COVID-19, and (3) nanoparticle vaccines against SARS-CoV-2. We discuss how nanoparticles are tailor-made to biointerface with the host and the virus in each category. For each nanoparticle design, we highlight its structure–function relationship that enables effective antiviral activity. Overall, nanoparticles bring numerous new opportunities to improve our response to the current COVID-19 pandemic and enhance our preparedness for future viral outbreaks.

Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition.

Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles (“cellular nanosponges”) mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that increasing surface heparin density on the cellular nanosponges can promote their inhibition against SARS-CoV-2. Specifically, cellular nanosponges are made with azido-expressing host cell membranes followed by conjugating heparin to the nanosponge surfaces. Cellular nanosponges with a higher heparin density have a larger binding capacity with viral S proteins and a significantly higher inhibition efficacy against SARS-CoV-2 infectivity. Overall, surface glycan engineering of host-mimicking cellular nanosponges is a facile method to enhance SARS-CoV-2 inhibition. This approach can be readily generalized to promote the inhibition of other glycan-dependent viruses.

Biomimetic immunomodulation by crosstalk with nanoparticulate regulatory T cells

<h2>Summary</h2> Hyperactive immunity mediates the development and progression of various immuno-inflammatory diseases. However, the use of immunosuppressive or anti-inflammatory agents has been largely restricted either by off-target side effects or by individual interaction site. Here, we describe a biomimetic manipulation strategy for immunosuppression by crosstalk with regulatory T (Treg) cell membrane-coated nanoparticles. Due to the reservation of intrinsic membrane proteins and function from Treg cells, coated nanoparticles can directly interact with multifaceted overactive immune cells. By virtue of this unique characteristic, nanoparticulate Treg cells inhibit macrophage-osteoclast differentiation, the maturation of dendritic cells, and the activation of effector T cells. In both murine and canine models of periodontitis, these nanoparticles successfully suppress excessive immune responses, alleviating inflammation and curbing alveolar bone resorption. Our work reveals how dysregulated immune responses can be effectively manipulated by biomimetic immunomodulation and proposes the utilization of nanoparticulate Treg cells as a promising approach to treat immuno-inflammatory diseases.

Surface PEGylated Cancer Cell Membrane-Coated Nanoparticles for Codelivery of Curcumin and Doxorubicin for the Treatment of Multidrug Resistant Esophageal Carcinoma

ObjectiveThe emergence of multi-drug resistance (MDR) in esophageal carcinoma has severely affected the effect of chemotherapy and shortened the survival of patients. To this end, we intend to develop a biomimetic nano-targeting drug modified by cancer cell membrane, and investigate its therapeutic effect.MethodsThe degradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with doxorubicin (DOX) and curcumin (Cur) were prepared by solvent evaporation method. TE10 cell membrane and Distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) were then coated on the PLGA NPs by membrane extrusion to prepare the PEG-TE10@PLGA@DOX-Cur NPs (PMPNs). Size and zeta potential of the PMPNs were analyzed by lazer particle analyzer, and the morphology of PMPNs was observed by transmission electron microscope. The TE10 cell membrane protein on PMPNs was analyzed by gel electrophoresis. The DOX-resistant esophageal cancer cell model TE10/DOX was established through high-dose induction. The In vitro homologous targeting ability of PMPNs was evaluated by cell uptake assay, and the in vitro anti-tumor effect of PMPNs was assessed through CCK-8, clone formation and flow cytometry. A Balb/c mouse model of TE10/DOX xenograft was constructed to evaluate the anti-tumor effect in vivo and the bio-safety of PMPNs.ResultsThe prepared cell membrane coated PMPNs had a regular spherical structure with an average diameter of 177 nm. PMPNs could directly target TE10 and TE10/DOX cells or TE10/DOX xenografted tumor and effectively inhibit the growth of DOX-resistant esophageal carcinoma. Besides, the PMPNs was confirmed to have high biosafety.ConclusionIn this study, a targeted biomimetic nano-drug delivery system PMPNs was successfully prepared, which overcome the MDR of esophageal carcinoma by co-delivering DOX and sensitizer curcumin.

Next Generation Immunotherapies – Emerging Strategies for Immune Modulation against Cancer, Infections, and Beyond

Next Generation Immunotherapies – Emerging Strategies for Immune Modulation against Cancer, Infections, and Beyond

Retraction of "Red Blood Cell Membrane-Coated Silica Nanoparticles Codelivering DOX and ICG for Effective Lung Cancer Therapy".

[This retracts the article DOI: 10.1021/acsomega.0c01541.].

Inside-Out-Oriented Cell Membrane Biomimetic Magnetic Nanoparticles for High-Performance Drug Lead Discovery.

Biomimetic cell membrane-coated nanoparticles have been broadly applied because of their superior biochemical properties. The right-side-out cell membrane coating manner provides nanoparticles with an immune-evasive stealth function in vivo. However, this acts as a drag for drug discovery when the drug targets are the intracellular domain of transmembrane receptors. Herein, inside-out-oriented cell membrane-coated nanoparticles were prepared for screening tyrosine kinase inhibitors, which specifically interacted with the intracellular kinase domain of the epidermal growth factor receptor. Biotinylated human lung adenocarcinoma epithelial cell membranes specifically interacted with streptavidin-immobilized Fe3O4 magnetic nanoparticles and then formed inside-out-oriented cell membrane-coated magnetic nanoparticles (IOCMMNPs). The cell membrane orientation of the IOCMMNPs was successfully confirmed by immunogold electron microscopy, fluorescently labeled confocal microscopy, sialic acid quantification assay, and the adsorption capacity assay. Moreover, IOCMMNPs possessed satisfactory binding capacity, selectivity, and high sensitivity (limit of detection = 0.4 × 10-3 μg mL-1). Ultimately, IOCMMNPs successfully targeted two main compounds from Strychnos nux-vomica whose potential antitumor activities were further validated by pharmacological studies. The application of the inside-out cell membrane coating strategy further enhances the drug screening efficiency and broadens the insight and methodologies for drug lead discovery. This inside-out cell membrane coating concept also provides a method for the future development of engineered cell membrane-coated nanotechnology.

A Polymer Multicellular Nanoengager for Synergistic NIR-II Photothermal Immunotherapy.

Cell-membrane-coated nanoparticles (CCNPs) that integrate the biophysiological advantages of cell membranes with the multifunctionalities of synthetic materials hold great promise in cancer immunotherapy. However, strategies have yet to be revealed to further improve their immunotherapeutic efficacy. Herein, a polymer multicellular nanoengager (SPNE) for synergistic second-near-infrared-window (NIR-II) photothermal immunotherapy is reported. The nanoengager consists of an NIR-II absorbing polymer as the photothermal core, which is camouflaged with fused membranes derived from immunologically engineered tumor cells and dendritic cells (DCs) as the cancer vaccine shell. In association with the high accumulation in lymph nodes and tumors, the multicellular engagement ability of the SPNE enables effective cross-interactions among tumor cells, DCs, and T cells, leading to augmented T cell activation relative to bare or tumor-cell-coated nanoparticles. Upon deep-tissue penetrating NIR-II photoirradiation, SPNE eradicates the tumor and induces immunogenic cell death, further eliciting anti-tumor T cell immunity. Such a synergistic photothermal immunotherapeutic effect eventually inhibits tumor growth, prevents metastasis and procures immunological memory. Thus, this study presents a general cell-membrane-coating approach to develop photo-immunotherapeutic agents for cancer therapy.

Immune Cell Membrane-Coated Biomimetic Nanoparticles for Targeted Cancer Therapy.

Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano-based systems coated with immune cells-derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.

CD4+ T cell-mimicking nanoparticles encapsulating DIABLO/SMAC mimetics broadly neutralize HIV-1 and selectively kill HIV-1-infected cells.

HIV-1 is a major global health challenge. The development of an effective vaccine and a therapeutic cure are top priorities. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 stymies this progress. Therapeutic strategies that provide effective and broad‐spectrum neutralization against HIV-1 infection are highly desirable.Methods: We investigated the potential of nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP) encapsulating the DIABLO/SMAC mimetics LCL-161 or AT-406 (also known as SM-406 or Debio 1143) to both neutralize HIV-1 and selectively kill HIV-1-infected resting CD4+ T cells and macrophages.Results: DIABLO/SMAC mimetic-loaded TNP displayed outstanding neutralizing breadth and potency, and selectively kill HIV-1-infected cells via autophagy-dependent apoptosis while having no drug-induced off-target or cytotoxic effects on bystander cells. Genetic inhibition of early stages of autophagy abolishes this effect.Conclusion: DIABLO/SMAC mimetic loaded TNP have the potential to be used as therapeutic agents to neutralize cell-free HIV-1 and to kill specifically HIV-1-infected cells as part of an HIV-1 cure strategy.

An electroporation strategy to synthesize the membrane-coated nanoparticles for enhanced anti-inflammation therapy in bone infection.

The cell membrane-coated nanoparticles (MNPs) showed great potential in treating infectious disease due to their superior biofunctions in improving biocompatibility of nanoparticles and neutralization of pathogen or toxins. However, bone infection is accompanied with severe inflammation and bone loss, which also requires anti-inflammatory and osteoconductive treatment. The conventional membrane coating method has to undergo ultrasonication and extrusion procedures, which reduces the functionality of cell membrane and limits the choice of nanoparticles. In this study, we proposed an electroporation-based membrane coating strategy to facilitate the synthesis of MNPs to tackle those problems.Methods: Magnetic composite nanoparticles with osteoconductive Ca3(PO4)2 and bactericidal TiO2 were assembled into macrophages through phagocytosis and then collected to expose in electric field for obtaining macrophage membrane-coating nanoparticles. By using molecular dynamics simulation and materials characterizations, the cell membrane coating efficiency was confirmed. The in vitro anti-bacterial and anti-inflammatory abilities were tested by bacteria culturing and immune cells activation. Then drug-resistant bacteria induced bone infection model was established to verify its in vivo therapeutic effects.Results: The coated membrane prepared through electroporation reserved the integrality of membrane structure and right-sidedness, with more functional proteins. Those led to the superior properties of recognition and adsorption with bacteria, toxins and inflammatory cytokines. Owing to the benefits of electroporation, the MNPs exhibited significant better antibacterial and anti-inflammatory abilities for enhancing the tissue repair process.Conclusion: This study provides a novel self-assembly cell membrane coating strategy by electroporation to construct multifunctional membrane-coating nanoparticles for bone infection treatment. This strategy not only improves the functions of coated membrane, but is also proved to be universal for varies nanoparticles or cells, indicating a great potential for future applications in the bioengineering field.

Hybrid-cell membrane-coated nanocomplex-loaded chikusetsusaponin IVa methyl ester for a combinational therapy against breast cancer assisted by Ce6.

Breast cancer is the most common cancer in women and occurs mostly with poor outcomes. Our objective was to endow synthetic lethality to the phytoconstituent chikusetsusaponin IVa methyl ester (CSME, S), a special phytoconstituent from traditional Chinese medicine (TCM), Panax japonicus, with the photodynamic agent chlorin e6 (Ce6, C) and enhance the therapeutic efficacy against breast cancer using cell membrane-coated liposome nanoparticles (liposome, L). The delivery system based on liposomes was camouflaged by a hybrid cell membrane (RBC membrane and cancer cell membrane, M) and RGD (R) surface modifications to improve the solubility, targeting and treatment outcomes of CSME. Our results showed the successful development of nanocomplexes with extended half-life, increased immune evasion and targeted ability at the tumor site and good antitumor activity without side effects to normal tissue. The anti-tumor mechanism of nanocomplexes is related to cell proliferation regulation and apoptosis induction. Overall, this drug-delivery system provides a good alternative for breast cancer therapy using a natural active phytoconstituent.

Doxorubicin and PD-L1 siRNA co-delivery with stem cell membrane-coated polydopamine nanoparticles for the targeted chemoimmunotherapy of PCa bone metastases.

Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA-DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA-DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA-DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.

Orchestration of biomimetic membrane coating and nanotherapeutics in personalized anticancer therapy.

Nanoparticle-based therapeutic and detectable modalities can augment anticancer efficiency, holding potential in capable target and suppressive metastases post administration. However, the individual discrepancies of the current "one-size-fits-all" strategies for anticancer nanotherapeutics have heralded the need for "personalized therapy". Benefiting from the special inherency of various cells, diverse cell membrane-coated nanoparticles (CMCNs) were established on a patient-by-patient basis, which would facilitate the personalized treatment of individual cancer patients. CMCNs in a complex microenvironment can evade the immune system and target homologous tumors with a suppressed immune response, as well as a prolonged circulation time, consequently increasing the drug accumulation at the tumor site and anticancer therapeutic efficacy. This review focuses on the emerging strategies and advances of CMCNs to synergistically integrate the merit of source cells with nanoparticulate delivery systems for the orchestration of personalized anticancer nanotherapeutics, thus discussing their rationalities in facilitating chemotherapy, imaging, immunotherapy, phototherapy, radiotherapy, sonodynamic, magnetocaloric, chemodynamic and gene therapy. Furthermore, the mechanism, challenges and opportunities of CMCNs in personalized anticancer therapy were highlighted to further boost cooperation from different fields, including materials science, chemistry, medicine, pharmacy and biology for the lab-to-clinic translation of CMCNs combined with the individual advantages of source cells and nanotherapeutics.

Recent advances in mesenchymal stem cell membrane-coated nanoparticles for enhanced drug delivery.

Studies of nanomedicine have achieved dramatic progress in recent decades. However, the main challenges that traditional nanomedicine has to overcome include low accumulation at target sites and rapid clearance from the blood circulation. An interesting approach using cell membrane coating technology has emerged as a possible way to overcome these limitations, owing to the enhanced targeted delivery and reduced immunogenicity of cell membrane moieties. Mesenchymal stem cell (MSC) therapy has been investigated for treating various diseases, ranging from inflammatory diseases to tissue damage. Recent studies with engineered modified MSCs or MSC membranes have focused on enhancing cell therapeutic efficacy. Therefore, bioengineering strategies that couple synthetic nanoparticles with MSC membranes have recently received much attention due to their homing ability and tumor tropism. Given the various membrane receptors on their surfaces, MSC membrane-coated nanoparticles are an effective method with selective targeting properties, allowing entry into specific cells. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for biomedical applications, particularly in the two main antitumor and anti-inflammatory fields. The combination of a bioengineered cell membrane and synthesized nanoparticles presents a wide range of possibilities for the further development of targeted drug delivery, showing the potential to enhance the therapeutic efficacy for treating various diseases.

Red Blood Cell Membrane-Coated Silica Nanoparticles Codelivering DOX and ICG for Effective Lung Cancer Therapy.

The effective chemotherapy of cancer is usually hindered by the unsatisfied cell internalization of the drug delivery systems (DDS) as well as drug resistance of cancer cells. In order to solve these dilemmas in one design, red blood cell membrane (RBM)-coated silica nanoparticles (RS) were fabricated to codeliver doxorubicin (Dox) and indocyanine green (ICG) to effectively treat the model lung cancer using photothermal-assisted chemotherapy. Our results demonstrated that the RS/I-D was the nanoparticle at around 100 nm with superior stability and biocompatibility. Especially, the photothermal effects of ICG were well preserved and could be applied to accelerate the drug release from the DDS. More importantly, the RBM modification can mediate enhanced cell internalization of drugs as compared to their free forms, which finally resulted in enhanced anticancer efficacy in Dox-resistant A549 cells (A549/Dox) both in vitro and in vivo with enhanced cell apoptosis and cell arrest.

Polydopamine Nanoparticles Camouflaged by Stem Cell Membranes for Synergistic Chemo-Photothermal Therapy of Malignant Bone Tumors.

PurposeNanoparticle (NP)-based chemo-photothermal therapy (CPT) has been shown to be a promising non-invasive approach for antitumor treatment. However, NPs must overcome the limitations of opsonization, clearance of the reticuloendothelial system, and ineffective targeting of tumor tissue sites. To solve these problems, stem cell membrane (SCM)-camouflaged polydopamine nanoparticles (PDA@SCM NPs) carrying the hydrophobic anticancer drug 7-ethyl-10-hydroxycamptothecin (SN38) were constructed for CPT of malignant bone tumors.MethodsWe developed umbilical-cord mesenchymal stem cell membrane-coated polydopamine nanoparticles encapsulating SN38 (PDA-SN38@SCM NPs) as an efficient tumor-targeting drug-delivery platform for CPT of malignant bone tumors. We characterized PDA@SCM NPs and evaluated the biocompatibility and anti-phagocytosis properties of PDA@SCM NPs. The antitumor activity of PDA-SN38@SCM NPs was evaluated in MG63 lines and an MG63 xenograft model in mice.ResultsSynthesized PDA-SN38@SCM NPs retained an excellent photothermal effect after SN38 loading. The drug release of PDA-SN38@SCM NPs could be triggered by near-infrared irradiation and an acidic stimulus. PDA@SCM NPs exhibited lower nonspecific macrophage uptake, longer retention in blood, and more effective accumulation at tumor sites than that shown by PDA NPs. Confocal laser scanning microscopy (CLSM) and flow cytometry showed that MG63 cells took up more PDA-SN38@SCM NPs than PDA-SN38 NPs. In vitro and in vivo antitumor studies demonstrated the outstanding performance of PDA-SN38@SCM NPs in synergistic CPT for bone tumors.ConclusionPDA-SN38@SCM NPs demonstrated an extraordinary synergistic CPT effect and could be a promising strategy for the treatment of malignant bone tumors.

A Review of Biomimetic Nanoparticle Drug Delivery Systems Based on Cell Membranes.

Cancers have always been an intractable problem because of recurrence and drug resistance. In the past few decades, nanoparticles have been explored intensely to diagnose, prevent and treat malignancy due to their good penetrability and better targeting. However, most nanocarriers have poor biodegradation and can be discharged out of the body quickly or cleared by immune cells while failing to obtain effective drug concentration at the specific sites. The emergence of biological membrane encapsulation technology relieves the fast clearance of antitumor drugs and reduces toxicity in vivo. This review will discuss the advantages and disadvantages of several blood cell membrane-coated nanoparticles and further introduce exosome-carried drugs to evidence the promising prospect of biomimetic nanoparticle drug delivery systems.

Application of Biomimetic Cell-Derived Nanoparticles with Mannose Modification as a Novel Vaccine Delivery Platform against Teleost Fish Viral Disease.

Although cell membrane-coated nanoparticles are widely used as a promising nanodelivery platform, a few studies reported their application in developing the teleost nanovaccine delivery system. Here, we present a biomimetic vaccine delivery platform by encapsulating chitosan-loaded DNA vaccine with teleost erythrocytes membrane modified by mannose. The developed CS-G@M-M nanovaccine delivery platform shows good biocompatibility in vivo and in vitro. With further modification of mannose moiety, the constructed CS-G@M-M showed enhanced uptake by antigen-presenting cells (APCs) and increased accumulation of CS-G@M-M in immune tissues including spleen, kidney, and hindgut. Critically, using a quantitative real-time polymerase chain reaction (qRT-PCR) assay, increased mRNA levels of immune-related genes were detected in spleen and hindgut of vaccinated fish. Moreover, through enzyme-linked immunosorbent assay (ELISA), we found that the levels of CD80/86, TNF-α, IgM, and IgZ in spleen and hindgut were significantly increased. To evaluate the immunoprotection efficacy of the constructed nanovaccine, spring viremia of carp virus (SVCV), a rhabdovirus of worldwide importance that requires notification within 48 h to the International Office of Epizootics once detected, was used as a model for virus challenge. We carried out three challenge tests on 3rd, 21st, and 70th days post vaccination, respectively. Notably, CS-G@M-M nanovaccine showed durability of immunoprotection efficacy that could protect zebrafish from SVCV challenge. This work presents a novel design of smart teleost erythrocytes membrane-coated nanoparticles, which are inherently biocompatible, promising for eliciting robust adaptive immune responses in preventing fish viral diseases.