scholarly journals Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lizhi Liu ◽  
Xuan Bai ◽  
Maria-Viola Martikainen ◽  
Anna Kårlund ◽  
Marjut Roponen ◽  
...  

AbstractCell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (<50%) need to aggregate together before internalization. This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.

2021 ◽  
Vol 7 (25) ◽  
pp. eabf7820
Author(s):  
Joon Ho Park ◽  
Yao Jiang ◽  
Jiarong Zhou ◽  
Hua Gong ◽  
Animesh Mohapatra ◽  
...  

As numerous diseases are associated with increased local inflammation, directing drugs to the inflamed sites can be a powerful therapeutic strategy. One of the common characteristics of inflamed endothelial cells is the up-regulation of vascular cell adhesion molecule–1 (VCAM-1). Here, the specific affinity between very late antigen–4 (VLA-4) and VCAM-1 is exploited to produce a biomimetic nanoparticle formulation capable of targeting inflammation. The plasma membrane from cells genetically modified to constitutively express VLA-4 is coated onto polymeric nanoparticle cores, and the resulting cell membrane–coated nanoparticles exhibit enhanced affinity to target cells that overexpress VCAM-1 in vitro. A model anti-inflammatory drug, dexamethasone, is encapsulated into the nanoformulation, enabling improved delivery of the payload to inflamed lungs and significant therapeutic efficacy in vivo. Overall, this work leverages the unique advantages of biological membrane coatings to engineer additional targeting specificities using naturally occurring target-ligand interactions.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3428
Author(s):  
Chaojie Zhu ◽  
Junkai Ma ◽  
Zhiheng Ji ◽  
Jie Shen ◽  
Qiwen Wang

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, causing approximately 17.9 million deaths annually, an estimated 31% of all deaths, according to the WHO. CVDs are essentially rooted in atherosclerosis and are clinically classified into coronary heart disease, stroke and peripheral vascular disorders. Current clinical interventions include early diagnosis, the insertion of stents, and long-term preventive therapy. However, clinical diagnostic and therapeutic tools are subject to a number of limitations including, but not limited to, potential toxicity induced by contrast agents and unexpected bleeding caused by anti-platelet drugs. Nanomedicine has achieved great advancements in biomedical area. Among them, cell membrane coated nanoparticles, denoted as CMCNPs, have acquired enormous expectations due to their biomimetic properties. Such membrane coating technology not only helps avoid immune clearance, but also endows nanoparticles with diverse cellular and functional mimicry. In this review, we will describe the superiorities of CMCNPs in treating cardiovascular diseases and their potentials in optimizing current clinical managements.


2021 ◽  
Author(s):  
Xuerui Chen ◽  
Bingbing Liu ◽  
Rongliang Tong ◽  
Lin Zhan ◽  
Xuelian Yin ◽  
...  

Benefiting from the special inherency of natural cells, diverse cell membrane-coated nanoparticles can facilitate personalized anticancer treatment.


2021 ◽  
Author(s):  
Lingling Wu ◽  
Qin Li ◽  
Junjie Deng ◽  
Weide Xu ◽  
Bingyu Chen ◽  
...  

Abstract Cell membrane-camouflaged nanoparticles are drawing increasing attention because their surfaces retain the natural functionalities of the cell plasma membranes, making them a unique class of biomimetic materials combining natural and synthetic components. Modifying the cell membranes or combining the functions of different types of membranes enhances their functionality. Herein, we prepared platelet and tumor cell membrane camouflaged antitumor nanoparticles. The effects of β-mangostin-loaded nanoparticles on the target and its anticancer action in glioma were measured in vitro and in vivo. Multifunctional nanoparticles were manufactured with platelet–C6 hybrid biomimetic coating (PCM), lactic-co-glycolic acid (PLGA), and β-mangostin. PCM increased the proportion of active drug targeting in C6 and immune escape characteristics in THP-1 cells, thus enhancing the cytotoxicity of β-PCNPs. The β-PCNPs were comprehensively characterized to study the inherent properties of both source cells. Compared with bare β-NPs, β-PCNPs exhibited high tumor-targeting ability and induced apoptosis of C6 cells in vitro. Mice experiments with intravenous administration of the drug revealed that the β-PCNP platform enhanced the tumor targeting capability and exhibited excellent chemotherapy with high inhibition rate of glioma tumor growth in vivo. The mice in the β-PCNP group had a markedly prolonged circulation lifetime and exhibited better outcome than those in the β-NP group. These 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.


2021 ◽  
Author(s):  
Fangjie Chen ◽  
Lu Wang ◽  
Jinyao Liu

Abstract Despite the activation of T lymphocytes by antigen-presenting cells is responsible for eliciting antigen-specific immune responses, their crosstalking suffers from temporospatial limitations and endogenous influencing factors, which restrict the generation of a strong antitumor immunity. Here, we describe the manipulation of cross-priming of T cells using biomimetic nanoparticles (BNs) enabled by cascade cell membrane coating. BNs are resulted from coating nanoparticulate substrates with cell membranes extracted from dendritic cells (DCs) that are pre-pulsed with cancer cell membrane-coated nanoparticles. With a DC membrane that presents an array of cancer cell membrane antigen epitopes, BNs inherit intrinsic membrane function of DCs. Strikingly, BNs can directly cross-prime T cells and provoke robust yet antigen-specific antitumor responses in multiple mouse models. Combination with clinical anti-programmed death-1 antibodies demonstrates a practical way of BNs to achieve desirable tumor regression and survival rate. This work spotlights the impact of nanoparticles on direct cross-priming of T cells and supports a unique yet modulate platform for boosting an effective adaptive immunity for immunotherapy.


2020 ◽  
Vol 8 (2) ◽  
pp. 552-568 ◽  
Author(s):  
Huaiji Wang ◽  
Ying Liu ◽  
Ruiqing He ◽  
Dailin Xu ◽  
Jie Zang ◽  
...  

Cell membrane coated nanoparticles have been designed for inflammation and cancer therapy. An array of cell membranes from cell library were extracted and leveraged to coat a variety of nanoparticles for different diseases.


Small ◽  
2021 ◽  
pp. 2104402
Author(s):  
Fangjie Chen ◽  
Zhongmin Geng ◽  
Lu Wang ◽  
Yan Zhou ◽  
Jinyao Liu

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 881 ◽  
Author(s):  
Haichun Li ◽  
Kai Jin ◽  
Man Luo ◽  
Xuejun Wang ◽  
Xiaowen Zhu ◽  
...  

Recently, biomimetic nanoparticles, especially cell membrane-cloaked nanoparticles, have attracted increasing attention in biomedical applications, including antitumor therapy, detoxification, and immune modulation, by imitating the structure and the function of biological systems such as long circulation life in the blood. However, the circulation time of cell membrane-cloaked nanoparticles is far less than that of the original cells, greatly limiting their biomedical applications, while the underlying reasons are seldom demonstrated. In this study, the influence of particle size on the circulation and the biodistribution of red blood cell membrane-coated nanoparticles (RBC-NPs) as model biomimetic nanoparticles were investigated. Differently sized RBC-NPs (80, 120, 160, and 200 nm) were prepared by fusing RBC membranes on poly(lactic-co-glycolic acid) nanoparticles. It was shown that the particle size did not change the cellular uptake of these biomimetic nanoparticles by macrophage cells in vitro and their immunogenic responses in vivo. However, their circulation life in vivo decreased with the particle size, while their accumulation in the liver increased with the particle size, which might be related to their size-dependent filtration through hepatic sinusoids. These findings will provide experimental evidence for the design and the optimization of biomimetic nanoparticles.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3136 ◽  
Author(s):  
Ruliang Wang ◽  
Han Yang ◽  
Rongxin Fu ◽  
Ya Su ◽  
Xue Lin ◽  
...  

Multimodal imaging-guided near-infrared (NIR) photothermal therapy (PTT) is an interesting and promising cancer theranostic method. However, most of the multimodal imaging systems provide structural and functional information used for imaging guidance separately by directly combining independent imaging systems with different detectors, and many problems arise when trying to fuse different modal images that are serially taken by inviting extra markers or image fusion algorithms. Further, most imaging and therapeutic agents passively target tumors through the enhanced permeability and retention (EPR) effect, which leads to low utilization efficiency. To address these problems and systematically improve the performance of the imaging-guided PTT methodology, we report a novel simultaneous dual-modal imaging system combined with cancer cell membrane-coated nanoparticles as a platform for PTT-based cancer theranostics. A novel detector with the ability to detect both high-energy X-ray and low-energy visible light at the same time, as well as a dual-modal imaging system based on the detector, was developed for simultaneous dual-modal imaging. Cancer cell membrane-coated upconversion nanoparticles (CC-UCNPs) and gold nanoparticles (CC-AuNPs) with the capacity for immune evasion and active tumor targeting were engineered for highly specific imaging and high-efficiency PTT therapy. In vitro and in vivo evaluation of macrophage escape and active homologous tumor targeting were performed. Cancer cell membrane-coated nanoparticles (CC-NPs) displayed excellent immune evasion ability, longer blood circulation time, and higher tumor targeting specificity compared to normal PEGylated nanoparticles, which led to highly specific upconversion luminescence (UCL) imaging and PTT-based anti-tumor efficacy. The anti-cancer efficacy of the dual-modal imaging-guided PTT was also evaluated both in vitro and in vivo. Dual-modal imaging yielded precise anatomical and functional information for the PTT process, and complete tumor ablation was achieved with CC-AuNPs. Our biomimetic UCNP/AuNP and novel simultaneous dual-modal imaging combination could be a promising platform and methodology for cancer theranostics.


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