Cell Membrane-derived Vesicles Research Articles

Stabilized Cell Membrane-Derived Vesicles by Lipid Anchoring for Enhanced Drug Delivery.

A cell membrane-derived vesicle (MV) that has cell-mimicking features with characteristic functionalities holds vast appeal for biomimetic nanomedicine and drug delivery but suffers from a major limitation of innate fragility and poor stability. Herein, we report a lipid-anchoring strategy for stabilizing MV for enhanced drug delivery. An array of amphiphilic mono-acyl phosphatidylcholines (MPCs) with specific hydrophobic moieties are synthesized and readily engineered on MV based on their commendable aqueous solubility and efficient membrane insertability. Incorporation of MPCs containing rigid ring structures in the hydrophobic segment demonstrates the potency of stabilizing MV by the combined ordering and condensing effects. The optimized MPC-stabilized MV exhibits prolonged circulation in the bloodstream, elevated accumulation within a tumor, and enhanced therapeutic effects of chemotherapeutic and photothermal drugs. Moreover, doxorubicin-loaded MV, engineered with mono-all-trans retinoyl phosphatidylcholine as an MV stabilizer and a therapeutic prodrug, potently suppresses growth and metastasis of high-stemness tumors.

Human glioblastoma-derived cell membrane nanovesicles: a novel, cell-specific strategy for boron neutron capture therapy of brain tumors

Glioblastoma (GBM), one of the deadliest brain tumors, accounts for approximately 50% of all primary malignant CNS tumors, therefore novel, highly effective remedies are urgently needed. Boron neutron capture therapy, which has recently repositioned as a promising strategy to treat high-grade gliomas, requires a conspicuous accumulation of boron atoms in the cancer cells. With the aim of selectively deliver sodium borocaptate (BSH, a 12 B atoms-including molecule already employed in the clinics) to GBM cells, we developed novel cell membrane-derived vesicles (CMVs), overcoming the limits of natural extracellular vesicles as drug carriers, while maintaining their inherent homing abilities that make them preferable to fully synthetic nanocarriers. Purified cell membrane fragments, isolated from patient-derived GBM stem-like cell cultures, were used to prepare nanosized CMVs, which retained some membrane proteins specific of the GBM parent cells and were devoid of potentially detrimental genetic material. In vitro tests evidenced the targeting ability of this novel nanosystem and ruled out any cytotoxicity. The CMVs were successfully loaded with BSH, by following two different procedures, i.e. sonication and electroporation, demonstrating their potential applicability in GBM therapy.

Determining native-like membrane protein structures from cell membrane-derived vesicles

Determining native-like membrane protein structures from cell membrane-derived vesicles

Harnessing genetically engineered cell membrane-derived vesicles as biotherapeutics

Cell membrane-derived vesicles (CMVs) are particles generated from living cells, including extracellular vesicles (EVs) and artificial extracellular vesicles (aEVs) prepared from cell membranes. CMVs possess considerable potential in drug delivery, regenerative medicine, immunomodulation, disease diagnosis, etc . owing to their stable lipid bilayer structure, favorable biocompatibility, and low toxicity. Although the majority of CMVs inherit certain attributes from the original cells, it is still difficult to execute distinct therapeutic functions, such as organ targeting, signal regulation, and exogenous biotherapeutic supplementation. Hence, engineering CMVs by genetic engineering, chemical modification, and hybridization is a promising way to endow CMVs with specific functions and open up novel vistas for applications. In particular, there is a growing interest in genetically engineered CMVs harnessed to exhibit biotherapeutics. Herein, we outline the preparation strategies and their characteristics for purifying CMVs. Additionally, we review the advances of genetically engineered CMVs utilized to target organs, regulate signal transduction, and deliver biomacromolecules and chemical drugs. Furthermore, we also summarize the emerging therapeutic applications of genetically engineered CMVs in addressing tumors, diabetes, systemic lupus erythematosus, and cardiovascular diseases.

Cancer Cell Membrane-Biomimetic Nanoparticles Based on Gelatin and Mitoxantrone for Synergetic Chemo-Photothermal Therapy of Metastatic Breast Cancer.

The purpose of this paper is to develop a cancer cell membrane biomimetic nanodrug delivery system (NDDS) to achieve an enhanced chemo-photothermal synergistic antitumor effect. The biomimetic NDDSs are composed of mitoxantrone (MIT)-loaded gelatin nanoparticles and IR820-encapsulated 4T1 cancer cell membrane-derived vesicles. The biomimetic NDDS displayed excellent stability and photothermal conversion efficiency. Compared to naked nanoparticles, the cell membrane-coated nanoparticles improved 4T1 cell uptake through homologous targeting and effectively reduced internalization of macrophages. In vivo photothermal imaging results further showed that the NDDS could be enriched at the tumor site for 48 h and could raise the temperature of the tumor area to 60 °C within 5 min under 808 nm laser irradiation. Finally, NDDS successfully inhibited primary tumor growth (over 89% inhibition) and significantly inhibited lung metastasis. This study may provide a new strategy for personalized chemotherapy-photothermal combination therapy of metastatic breast cancer using tumor cell membranes from cancer patients as drug carriers.

Nanomedicine Redefining Cancer Therapeutics: The Evolution of Precision Drug Delivery Systems

With the advent of nanomedicines including drug delivery carriers such as nanoparticles, liposomes, nanoemulsions, and micelles, there has been a paradigm shift in the sphere of cancer treatment. These nano-biosystems have been the focus of scientific research in recent years due to their biocompatibility, low toxicity, higher retention time, bioavailability and higher targeted efficiency as compared to conventional therapeutics such as chemotherapy, radiotherapy and immunotherapy. These conventional therapies not only target cancerous cells but negatively affect neighboring health cells as well comprising the individuals’ immune health. Therefore, nanomaterials have been considered the foremost strategy to combat different types of cancer. To facilitate delivery and provide a “stealthy character” to nanomaterials, biomimetic (cell-derived) surface coatings and encapsulations have been developed. Red blood cell mimetic nanoparticles have been designed to successfully inhibit the growth and metastasis of breast carcinoma. Similarly, HeLa cell membrane-derived vesicles of GdTPP/ZnTPP porphyrin nanocomposites have been utilized for photodynamic therapy (PDT) for cervical carcinoma [1]. In addition, ferritin-based and vault-protein nanocarriers have been designed using recombinant engineering techniques to overcome the barriers of multidrug resistance and in-vivo drug delivery reducing immune response and increasing the effectiveness of anticancerous drugs. These functionalized nanocarriers have been reported against glioma, melanoma, hepatocarcinoma, adenocarcinoma and lung cancer [2]. A considerable number of nanomedicines have passed clinical trials and been approved for commercial use by various regulatory organizations. The most recent being the NanoTherm, an EMA-approved nanomedicine for glioblastoma, prostate cancer, and pancreatic cancer. It is a superparamagnetic iron oxide nanoparticle covered with aminosilane [3]. With precision, efficacy, and promise for both patients and clinicians, nanomedicine is a sign of a new era in cancer therapies. Harnessing the potential of nanomedicine demands teamwork, innovation, and transforming ground-breaking research into game-changing clinical applications as we navigate this rapidly changing landscape. With the goal of bringing targeted, personalized cancer treatments closer to reality, this editorial seeks to highlight the unmatched potential of nanomedicine in transforming drug delivery paradigms. 

Biomimetic photosynthetic system: Shedding light on the restoration of cell metabolism

Biomimetic photosynthetic system: Shedding light on the restoration of cell metabolism

Profiling and analysis of exosomal miRNAs derived from highly pathogenic avian influenza virus H5N1-infected White Leghorn chickens

Exosomes are small cell membrane-derived vesicles; they play important roles as mediators of cell-to-cell communication via delivery of their contents, such as proteins and microRNAs (miRNAs). In particular, exosomal miRNAs regulate the gene expression of recipient cells by inhibiting the expression of target mRNAs. In this study, we investigated the miRNA expression profiles of highly pathogenic avian influenza virus (HPAIV) H5N1-infected White Leghorn chickens and analyzed the functions of their target genes. After 3 d of infection with A/chicken/Vietnam/NA-01/2019 (H5N1), exosomes were isolated from the blood serum of White Leghorn chickens for small RNA sequencing. We accordingly identified 10 differentially expressed miRNAs (DE miRNAs; 5 upregulated and 5 downregulated) by comparing the exosomes derived from infected and noninfected chickens. The target genes of DE miRNAs were predicted using miRDB and TargetScan for Gene Ontology and KEGG pathway enrichment analyses. A majority of the target genes was found to be associated with the MAPK signaling pathway; several immune-related genes were identified as being regulated by these DE miRNAs. Moreover, we predicted DE miRNA binding sites in HPAIV RNA segments using the RNAhybrid algorithm. The findings of this study provide a theoretical basis for gaining insights into the regulatory mechanisms of exosomal miRNAs in response to HPAIV H5N1 infection and the identification of novel vaccine candidates.

A Variant Allele in Varicella-Zoster Virus Glycoprotein B Selected during Production of the Varicella Vaccine Contributes to Its Attenuation.

Attenuation of the live varicella Oka vaccine (vOka) has been attributed to mutations in the genome acquired during cell culture passage of pOka (parent strain); however, the precise mechanisms of attenuation remain unknown. Comparative sequence analyses of several vaccine batches showed that over 100 single-nucleotide polymorphisms (SNPs) are conserved across all vaccine batches; 6 SNPs are nearly fixed, suggesting that these SNPs are responsible for attenuation. By contrast, prior analysis of chimeric vOka and pOka recombinants indicates that loci other than these six SNPs contribute to attenuation. Here, we report that pOka consists of a heterogenous population of virus sequences with two nearly equally represented bases, guanine (G) or adenine (A), at nucleotide 2096 of the ORF31 coding sequence, which encodes glycoprotein B (gB) resulting in arginine (R) or glutamine (Q), respectively, at amino acid 699 of gB. By contrast, 2096A/699Q is dominant in vOka (>99.98%). gB699Q/gH/gL showed significantly less fusion activity than gB699R/gH/gL in a cell-based fusion assay. Recombinant pOka with gB669Q (rpOka_gB699Q) had a similar growth phenotype as vOka during lytic infection in cell culture including human primary skin cells; however, rpOka_gB699R showed a growth phenotype similar to pOka. rpOka_gB699R entered neurons from axonal terminals more efficiently than rpOka_gB699Q in the presence of cell membrane-derived vesicles containing gB. Strikingly, when a mixture of pOka with both alleles equally represented was used to infect human neurons from axon terminals, pOka with gB699R was dominant for virus entry. These results identify a variant allele in gB that contributes to attenuation of vOka. IMPORTANCE The live-attenuated varicella vaccine has reduced the burden of chickenpox. Despite its development in 1974, the molecular basis for its attenuation is still not well understood. Since the live-attenuated varicella vaccine is the only licensed human herpesvirus vaccine that prevents primary disease, it is important to understand the mechanism for its attenuation. Here we identify that a variant allele in glycoprotein B (gB) selected during generation of the varicella vaccine contributes to its attenuation. This variant is impaired for fusion, virus entry into neurons from nerve terminals, and replication in human skin cells. Identification of a variant allele in gB, one of the essential herpesvirus core genes, that contributes to its attenuation may provide insights that assist in the development of other herpesvirus vaccines.

Cell Membrane-Derived Vesicle: A Novel Vehicle for Cancer Immunotherapy.

As nano-sized materials prepared by isolating, disrupting and extruding cell membranes, cellular vesicles are emerging as a novel vehicle for immunotherapeutic drugs to activate antitumor immunity. Cell membrane-derived vesicles inherit the surface characteristics and functional properties of parental cells, thus having superior biocompatibility, low immunogenicity and long circulation. Moreover, the potent antitumor effect of cellular vesicles can be achieved through surface modification, genetic engineering, hybridization, drug encapsulation, and exogenous stimulation. The capacity of cellular vesicles to combine drugs of different compositions and functions in physical space provides a promising vehicle for combinational immunotherapy of cancer. In this review, the latest advances in cellular vesicles as vehicles for combinational cancer immunotherapy are systematically summarized with focuses on manufacturing processes, cell sources, therapeutic strategies and applications, providing an insight into the potential and existing challenges of using cellular vesicles for cancer immunotherapy.

Nanoparticulate strategies for thedelivery of miRNA mimics and inhibitors in anticancer therapy and its potential utility in oral submucous fibrosis.

MicroRNAs (miRNAs) are naturally occurring noncoding RNAs with multiple functionalities. They are dysregulated in several conditions and can serve as disease biomarkers, therapeutic targets andtherapeutic agents. Translation of miRNA therapeutics to the clinic poses several challenges related to the safe and effective delivery of these agents to the site of action. Nanoparticulate carriers hold promise in this area by enhancing targeting efficiency and reducing off-target effects. This paper reviews recent advances in thedelivery strategies of miRNAs in anticancer therapy, with a focus on lipid-based, polymeric, inorganic platforms, cell membrane-derived vesicles and bacterial minicells. Additionally, this review explores the potentiality of miRNAs in the treatment of oral submucous fibrosis, a potentially premalignant condition of the oral cavity with no definitive treatment to date.

Extracellular Vesicles Physiological Role and the Particular Case of Disease-Spreading Mechanisms in Polyglutamine Diseases.

Recent research demonstrated pathological spreading of the disease-causing proteins from one focal point across other brain regions for some neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. Spreading mediated by extracellular vesicles is one of the proposed disease-spreading mechanisms. Extracellular vesicles are cell membrane-derived vesicles, used by cells for cell-to-cell communication and excretion of toxic components. Importantly, extracellular vesicles carrying pathological molecules, when internalized by “healthy” cells, may trigger pathological pathways and, consequently, promote disease spreading to neighboring cells. Polyglutamine diseases are a group of genetic neurodegenerative disorders characterized by the accumulation of mutant misfolded proteins carrying an expanded tract of glutamines, including Huntington’s and Machado–Joseph disease. The pathological spread of the misfolded proteins or the corresponding mutant mRNA has been explored. The understanding of the disease-spreading mechanism that plays a key role in the pathology progression of these diseases can result in the development of effective therapeutic approaches to stop disease progression, arresting the spread of the toxic components and disease aggravation. Therefore, the present review’s main focus is the disease-spreading mechanisms with emphasis on polyglutamine diseases and the putative role played by extracellular vesicles in this process.

COVID-19 Pandemic: A Case for Phytomedicines.

Coronavirus disease 2019 (COVID-19) is an infection caused by a newly discovered coronavirus which was identified in Wuhan, China. The race is on globally to repurpose drugs for COVID-19 and develop a safe and effective vaccine against the disease. There is an urgent need to search for effective remedies against COVID-19 from the rich and extensive flora of Africa and the world. A literature search was conducted to obtain information on drugs with the potential for effectiveness in the treatment of COVID-19 based mostly on outcomes of preclinical studies and a few clinical investigations. This was considered important to this perspective as some of the identified mechanisms of action may be related to potential anti-COVID-19 actions of phytomedicines. The findings from the literature search were also used to establish the need for exploration of phytomedicines in the fight against COVID-19. This perspective identifies the need to preserve the rich tradition of herbal medicine in Africa, repositioning it by inculcating all aspects of discovery, development, and chemical evaluation of pharmaceuticals from medicinal plants for effective management of prevalent diseases. The identified mechanisms of action of current drugs under consideration for the treatment of COVID-19 include preventing fusion of SARS-CoV-2 with human cells; decrease acidity in endosomes, cell membrane-derived vesicles for transportation of the virus within the host cell and within which the virus can replicate; and blockade of the production of proinflammatory cytokines. Phytomedicines may possibly elicit either one or a combination of these effects. The case for the exploration of phytomedicines against COVID-19 is strengthened by the emergence of a number of conventional drugs from medicinal plants and the emergence of botanicals with proven efficacy for some medical conditions. Caution against indiscriminate use of medicinal plants in the guise of treating COVID-19 has been highlighted and the need for reliable preclinical and clinical studies.

Preparation and evaluation of long circulating erythrocyte membrane-cloaked anti-cancer drug delivery system.

Recently, biomimetic hybrid drug delivery systems, especially erythrocyte membrane-based drug delivery systems, have been utilized to achieve high bioavailability, and biocompatibility, in the meantime, to reduce immunogenicity and effectively evade phagocytosis of the host immune system. Here, we developed a novel drug delivery system of red blood cell membrane-derived vesicles (RDVs) cloaked poly (acrylic acid)-cystamine hydrochloride-D-α-tocopherol succinate (PAAssVES) nanoparticles. The PAAssVES nanoparticles were prepared via emulsification and solvent volatilization method, followed by loading of the model anti-cancer drug, sorafenib (SFN). Then RDVs and SFN-PAAssVES nanoparticles were uniformly mixed and co-extruded through polycarbonate membrane. The prepared RDV-coated nanoparticles (RDV-NPs) had good stability, with a zeta potential of - 10.7mV and particle size of 113.5nm. MTT assay was used to analyze the effects of RDV-NPs on cell viability in two kinds of gastric cancer cell lines BGC-823 and MKN-45. The results showed that RDV-NPs significantly decreased cell viability. In vitro drug release investigation showed that RDV-NPs had good sustained release properties and the cumulative release was 71.5% in 72h. In pharmacokinetic studies, SD male rats' intravenous injection with RDV-NP solution showed a more smooth plasma concentration-time profile. Compared with free SFN treatment and SFN-PAAssVES group, RDV-NPs enhanced the AUC by about 4.1-fold and 2.0-fold. The MRT and t1/2 of RDV-NPs were increased to 23.670 ± 2.347h and 24.450 ± 2.652h. Our study demonstrated the promise of using RDV-NPs as a long circulating anti-cancer drug delivery system. Graphical abstract.

Nanocarriers for Stroke Therapy: Advances and Obstacles in Translating Animal Studies.

The technology of drug delivery systems (DDS) has expanded into many applications, such as for treating neurological disorders. Nanoparticle DDS offer a unique strategy for targeted transport and improved outcomes of therapeutics. Stroke is likely to benefit from the emergence of this technology though clinical breakthroughs are yet to manifest. This review explores the recent advances in this field and provides insight on the trends, prospects and challenges of translating this technology to clinical application. Carriers of diverse material compositions are presented, with special focus on the surface properties and emphasis on the similarities and inconsistencies among in vivo experimental paradigms. Research attention is scattered among various nanoparticle DDS and various routes of drug administration, which expresses the lack of consistency among studies. Analysis of current literature reveals lipid- and polymer-based DDS as forerunners of DDS for stroke; however, cell membrane-derived vesicles (CMVs) possess the competitive edge due to their innate biocompatibility and superior efficacy. Conversely, inorganic and carbon-based DDS offer different functionalities as well as varied capacity for loading but suffer mainly from poor safety and general lack of investigation in this area. This review supports the existing literature by systematizing presently available data and accounting for the differences in drugs of choice, carrier types, animal models, intervention strategies and outcome parameters.

Acute effects of haemodialysis on circulating microparticles.

BackgroundMicroparticles (MPs) are small cell membrane-derived vesicles regarded as both biomarkers and mediators of biological effects. Elevated levels of MPs have previously been associated with endothelial dysfunction and predict cardiovascular death in patients with end-stage renal disease. The objective of this study was to measure change in MP concentrations in contemporary haemodialysis (HD).MethodsBlood was sampled from 20 consecutive HD patients before and 1 h into the HD session. MPs were measured by flow cytometry and phenotyped based on surface markers.ResultsConcentrations of platelet (CD41+) (P = 0.039), endothelial (CD62E+) (P = 0.004) and monocyte-derived MPs (CD14+) (P < 0.001) significantly increased during HD. Similarly, endothelial- (P = 0.007) and monocyte-derived MPs (P = 0.001) expressing tissue factor (TF) significantly increased as well as MPs expressing Klotho (P = 0.003) and receptor for advanced glycation end products (RAGE) (P = 0.009). Furthermore, MPs expressing platelet activation markers P-selectin (P = 0.009) and CD40L (P = 0.045) also significantly increased. The increase of endothelial (P = 0.034), monocyte (P = 0.014) and RAGE+ MPs (P = 0.032) as well as TF+ platelet-derived MPs (P = 0.043) was significantly higher in patients treated with low-flux compared with high-flux dialysers.ConclusionDialysis triggers release of MPs of various origins with marked differences between high-flux and low-flux dialysers. The MPs carry surface molecules that could possibly influence coagulation, inflammation, oxidative stress and endothelial dysfunction. The clinical impact of these findings remains to be established in future studies.

Bioengineered cellular and cell membrane-derived vehicles for actively targeted drug delivery: So near and yet so far.

Cellular carriers for drug delivery are attractive alternatives to synthetic nanoparticles owing to their innate homing/targeting abilities. Here, we review molecular interactions involved in the homing of Mesenchymal stem cells (MSCs) and other cell types to understand the process of designing and engineering highly efficient, actively targeting cellular vehicles. In addition, we comprehensively discuss various genetic and non-genetic strategies and propose futuristic approaches of engineering MSC homing using micro/nanotechnology and high throughput small molecule screening. Most of the targeting abilities of a cell come from its plasma membrane, thus, efforts to harness cell membranes as drug delivery vehicles are gaining importance and are highlighted here. We also recognize and report the lack of detailed characterization of cell membranes in terms of safety, structural integrity, targeting functionality, and drug transport. Finally, we provide insights on future development of bioengineered cellular and cell membrane-derived vesicles for successful clinical translation.

Absolute quantification of microparticles by flow cytometry in ascites of patients with decompensated cirrhosis: a cohort study

BackgroundMicroparticles (MPs) are small (<1 μm) cell membrane-derived vesicles that are formed in response to cellular activation or early stages of apoptosis. Increased plasma MP levels have been associated with liver disease severity. Here we investigated the clinical impact of ascites MPs in patients with decompensated liver cirrhosis.MethodsAscites and blood samples of 163 patients with cirrhosis (ascites n = 163, blood n = 31) were collected between February 2011 and December 2012. MPs were obtained from ascites and from blood by two-step ultracentrifugation and quantified by flow cytometry. Quantitative absolute MP levels were correlated with clinical and laboratory baseline parameters as well as patient outcomes. Ascites microparticles were stained with antibodies against CD66b (neutrophils) and CD3 (lymphocytes) in a subgroup of 60 matched patients.ResultsMPs were detected in all ascites and blood samples. Absolute ascites MP levels correlated with blood levels (r = 0.444, p = 0.011). Low ascites MP levels (<488.4 MP/μL) were associated with a poor 30-day survival probability (<488.4 MP/μL 71.1% vs. >488.4 MP/μL 94.7%, log rank p = 0.001) and such patients had a higher relative amount of ascites microparticles derived from neutrophils and lymphocytes. Low levels of ascites MPs, high MELD score and antibiotic treatment were independent risk factors for death within 30 days.ConclusionsAscites MP levels predict short-term survival along with the liver function in patients with decompensated cirrhosis. Further studies which evaluate ascites MPs as disease specific biomarker with a validation cohort and which investigate its underlying mechanisms are needed. Neutrophils and lymphocytes contributed more frequently to the release of microparticles in patients with low ascites levels, possibly indicating an immune activation in this cohort.

Microfluidic Electroporation-Facilitated Synthesis of Erythrocyte Membrane-Coated Magnetic Nanoparticles for Enhanced Imaging-Guided Cancer Therapy

Biomimetic cell membrane-coated nanoparticles (CM-NPs) with superior biochemical properties have been broadly utilized for various biomedical applications. Currently, researchers primarily focus on using ultrasonic treatment and mechanical extrusion to improve the synthesis of CM-NPs. In this work, we demonstrate that microfluidic electroporation can effectively facilitate the synthesis of CM-NPs. To test it, Fe3O4 magnetic nanoparticles (MNs) and red blood cell membrane-derived vesicles (RBC-vesicles) are infused into a microfluidic device. When the mixture of MNs and RBC-vesicles flow through the electroporation zone, the electric pulses can effectively promote the entry of MNs into RBC-vesicles. After that, the resulting RBC membrane-capped MNs (RBC-MNs) are collected from the chip and injected into experimental animals to test the in vivo performance. Owing to the superior magnetic and photothermal properties of the MN cores and the long blood circulation characteristic of the RBC membrane shells, core-shell RBC-MNs were used for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Due to the completer cell membrane coating, RBC-MNs prepared by microfluidic electroporation strategy exhibit significantly better treatment effect than the one fabricated by conventional extrusion. We believe the combination of microfluidic electroporation and CM-NPs provides an insight into the synthesis of bioinpired nanoparticles to improve cancer diagnosis and therapy.

Synthesis of Nanogels via Cell Membrane-Templated Polymerization.

The synthesis of biomimetic hydrogel nanoparticles coated with a natural cell membrane is described. Compared to the existing strategy of wrapping cell membranes onto pre-formed nanoparticle substrates, this new approach forms the cell membrane-derived vesicles first, followed by growing nanoparticle cores in situ. It adds significant controllability over the nanoparticle properties and opens unique opportunities for a broad range of biomedical applications.