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Aptamers are short DNA or RNA sequences that adopt 3D structures and can bind to protein targets with high binding affinity and specificity. Aptamers exhibit excellent tissue penetration, are inexpensive to produce, and can be internalized by cells. Therefore, aptamers are attractive targeting ligands to direct the delivery of theranostic agents to the desired cells. Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen that is aberrantly overexpressed on many epithelial-derived cancers, including on cholangiocarcinoma (CCA) cells. Its expression on treatment-resistant cancer stem cells, along with its abundance in the CCA tumor microenvironment, highlights the need to develop EpCAM-targeted therapies for CCA. Herein, an in silico approach was used to design and screen DNA aptamers capable of binding to the EpCAM monomer and homodimer. Two aptamers, PLD01 and PLD02, met the selection criteria and were validated in vitro. Both aptamers exhibited high affinity for EpCAM+ CCA cells, with negligible binding to EpCAM- leukemia cells. Modified versions of PLD01 and PLD02 were successfully incorporated into the membranes of milk-derived nanovesicles. PLD01-functionalized nanovesicles enabled EpCAM-targeted delivery of the therapeutic cargo to CCA cells. In summary, these EpCAM-targeting aptamers can be utilized to direct the delivery of theranostic agents to EpCAM-expressing cells. [ABSTRACT FROM AUTHOR]

Vesicle, a microscopic unit that encloses a volume with an ultrathin wall, is ubiquitous in biomaterials. However, it remains a huge challenge to create its inorganic metal-based artificial counterparts. Here, inspired by the formation of biological vesicles, we proposed a novel biomimetic strategy of curling the ultrathin nanosheets into nanovesicles, which was driven by the interfacial strain. Trapped by the interfacial strain between the initially formed substrate Rh layer and subsequently formed RhRu overlayer, the nanosheet begins to deform in order to release a certain amount of strain. Density functional theory (DFT) calculations reveal that the Ru atoms make the curling of nanosheets more favorable in thermodynamics applications. Owing to the unique vesicular structure, the RhRu nanovesicles/C displays excellent hydrogen oxidation reaction (HOR) activity and stability, which has been proven by both experiments and DFT calculations. Specifically, the HOR mass activity of RhRu nanovesicles/C are 7.52 A mg(Rh+Ru)−1 at an overpotential of 50 mV at the rotating disk electrode (RDE) level; this is 24.19 times that of commercial Pt/C (0.31 mA mgPt−1). Moreover, the hydroxide exchange membrane fuel cell (HEMFC) with RhRu nanovesicles/C displays a peak power density of 1.62 W cm−2 in the H2-O2 condition, much better than that of commercial Pt/C (1.18 W cm−2). This work creates a new biomimetic strategy to synthesize inorganic nanomaterials, paving a pathway for designing catalytic reactors. [ABSTRACT FROM AUTHOR]

Abstract Imperceptible examination and unideal treatment effect are still intractable difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). At present, despite 5-fluorouracil (5-FU), as a clinical first-line FOLFIRINOX chemo-drug, has achieved significant therapeutic effects. Nevertheless, these unavoidable factors such as low solubility, lack of biological specificity and easy to induce immunosuppressive surroundings formation, severely limit their treatment in PDAC. As an important source of energy for many tumor cells, tryptophan (Trp), is easily degraded to kynurenine (Kyn) by indolamine 2,3- dioxygenase 1 (IDO1), which activates the axis of Kyn-AHR to form special suppressive immune microenvironment that promotes tumor growth and metastasis. However, our research findings that 5-FU can induce effectively immunogenic cell death (ICD) to further treat tumor by activating immune systems, while the secretion of interferon-γ (IFN-γ) re-induce the Kyn-AHR axis activation, leading to poor treatment efficiency. Therefore, a metal matrix protease-2 (MMP-2) and endogenous GSH dual-responsive liposomal-based nanovesicle, co-loading with 5-FU (anti-cancer drug) and NLG919 (IDO1 inhibitor), was constructed (named as ENP919@5-FU). The multifunctional ENP919@5-FU can effectively reshape the tumor immunosuppression microenvironment to enhance the effect of chemoimmunotherapy, thereby effectively inhibiting cancer growth. Mechanistically, PDAC with high expression of MMP-2 will propel the as-prepared nanovesicle to dwell in tumor region via shedding PEG on the nanovesicle surface, effectively enhancing tumor uptake. Subsequently, the S-S bond containing nanovesicle was cut via high endogenous GSH, leading to the continued release of 5-FU and NLG919, thereby enabling circulating chemoimmunotherapy to effectively cause tumor ablation. Moreover, the combination of ENP919@5-FU and PD-L1 antibody (αPD-L1) showed a synergistic anti-tumor effect on the PDAC model with abdominal cavity metastasis. Collectively, ENP919@5-FU nanovesicle, as a PDAC treatment strategy, showed excellent antitumor efficacy by remodeling tumor microenvironment to circulate tumor chemoimmunotherapy amplification, which has promising potential in a precision medicine approach.

Objective: The nanovesicle derived from hum, an umbilical cord mesenchymal stem cells (HUC-MSCs) can be used for drug targeting through a variety of methods. The aim of this study is to construct the CD64 (FcγRI) coated nanovesicle from the HUC-MSCs, and to detect the efficiency of antibodies (IgG1/IgG3) loading and cell entry of the nanovesicle. Methods: HUC-MSCs were isolated by tissue-cutting and cell culture method; A pLV-CD64 lentivirus packaging vector was established and packaged in the lentivirus; The lentivirus was transfected into HUC-MSCs, and the cell line that stably express CD64 was selected; The CD64 expressing HUC-MSCs was denuclearizated using the cytochalasin B co-incubation/centrifugation method; The nanovesicle with a diameter of approximately 200 nm was generated by ultrasound and gradient extrusion methods. The nanovesicle was co-incubated with anti-EGFR IgG1 antibodies for antibody loading, and the entry efficiency of the nanovesicle was investigated in A549 cells. Results: The nanovesicle with the diameter of 195± 82 nm, was obtained using the cytoplast of HUC-MSCs. The nanovesicle was stably expressing CD64 and successfully loaded with EGFR antibody; The modification effectively improved the entry efficiency of the nanovesicle for target cells. Conclusions: A nanovesicle with the capable of loading IgG1 antibodies was constructed, which could efficiently improve its entry efficiency for target cells. [ABSTRACT FROM AUTHOR]

Alveolar echinococcosis (AE) is a zoonotic parasitic disease, resulting from being infected with the metacestode larvae of the tapeworm Echinococcus multilocularis (E. multilocularis). Novel prophylactic and therapeutic interventions are urgently needed since the current chemotherapy displays limited efficiency in AE treatment. Bioengineered nano cellular membrane vesicles are widely used for displaying the native conformational epitope peptides because of their unique structure and biocompatibility. In this study, four T‐cells and four B‐cells dominant epitope peptides of E. multilocularis with high immunogenicity were engineered into the Vero cell surface to construct a membrane vesicle nanovaccine for the treatment of AE. The results showed that the nanovesicle vaccine can efficiently activate dendritic cells, induce specific T/B cells to form a mutually activated circuit, and inhibit E. multilocularis infection. This study presents for the first time a nanovaccine strategy that can completely eliminate the burden of E. multilocularis. [ABSTRACT FROM AUTHOR]

Aptamers are short DNA or RNA sequences that adopt 3D structures and can bind to protein targets with high binding affinity and specificity. Aptamers exhibit excellent tissue penetration, are inexpensive to produce, and can be internalized by cells. Therefore, aptamers are attractive targeting ligands to direct the delivery of theranostic agents to the desired cells. Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen that is aberrantly overexpressed on many epithelial-derived cancers, including on cholangiocarcinoma (CCA) cells. Its expression on treatment-resistant cancer stem cells, along with its abundance in the CCA tumor microenvironment, highlights the need to develop EpCAM-targeted therapies for CCA. Herein, an in silico approach was used to design and screen DNA aptamers capable of binding to the EpCAM monomer and homodimer. Two aptamers, PLD01 and PLD02, met the selection criteria and were validated in vitro. Both aptamers exhibited high affinity for EpCAM+ CCA cells, with negligible binding to EpCAM- leukemia cells. Modified versions of PLD01 and PLD02 were successfully incorporated into the membranes of milk-derived nanovesicles. PLD01-functionalized nanovesicles enabled EpCAM-targeted delivery of the therapeutic cargo to CCA cells. In summary, these EpCAM-targeting aptamers can be utilized to direct the delivery of theranostic agents to EpCAM-expressing cells.

[Display omitted] Engineered T cells expressing chimeric antigen receptor (CAR) exhibit high response rates in B-cell malignancy treatments and possess therapeutic potentials against various diseases. However, the complicated ex vivo production process of CAR-T cells limits their application. Herein, we use virus-mimetic fusogenic nanovesicles (FuNVs) to produce CAR-T cells in vivo via membrane fusion-mediated CAR protein delivery. Briefly, the FuNVs are modified using T-cell fusogen, adapted from measles virus or reovirus fusogens via displaying anti-CD3 single-chain variable fragment. The FuNVs can efficiently fuse with the T-cell membrane in vivo , thereby delivering the loaded anti-CD19 (αCD19) CAR protein onto T-cells to produce αCD19 CAR-T cells. These αCD19 CAR-T cells alone or in combination with anti-OX40 antibodies can treat B-cell lymphoma without inducing cytokine release syndrome. Thus, our strategy provides a novel method for engineering T cells into CAR-T cells in vivo and can further be employed to deliver other therapeutic membrane proteins. [ABSTRACT FROM AUTHOR]

Plant-derived exosome-like nanovesicles carry a variety of bioactive substances and have multiple health benefits. Pomegranate (Punica granatum) is a popular fruit with hepatoprotective effects. However, the effects of pomegranate-derived exosome-like nanovesicles (PENs) on nonalcoholic fatty liver disease (NAFLD) are still unknown. Here, PENs were successfully isolated and characterized, and found to be internalized by HepG2 cells. Interestingly, PENs survived gastrointestinal environment and ameliorated lipid accumulation as well as mitochondrial dysfunction in palmitic acid (PA)-treated HepG2 cells. Importantly, oral administration of PENs accumulated in the liver of mice and effectively alleviated high-fat diet (HFD)-induced NAFLD by improving mitochondrial function, as evidenced by improvements of ATP content, mitochondrial complex I activity and oxidative stress. Moreover, PENs restored SIRT3/SOD2 signaling and improved SOD2 activity in the liver of HFD-fed mice. These findings provide new mechanistic insights into pomegranate’s hepatoprotection and demonstrate the therapeutic potential of PENs for NAFLD.

The CD47/PD‐L1 antibodies combination exhibits durable antitumor immunity but also elicits excessive immune‐related adverse events (IRAEs) caused by the on‐target off‐tumor immunotoxicity, hindering their clinical benefits greatly. Here, a microfluidics‐enabled nanovesicle using ultra‐pH‐sensitive polymer mannose‐poly(carboxybetaine methacrylate)‐poly(hydroxyethyl piperidine methacrylate) (Man‐PCB‐PHEP) is developed to deliver CD47/PD‐L1 antibodies (NCPA) for tumor‐acidity‐activated immunotherapy. The NCPA can specifically release antibodies in acidic environment, thereby stimulating the phagocytosis of bone marrow‐derived macrophages. In mice bearing Lewis lung carcinoma, NCPA shows significantly improved intratumoral CD47/PD‐L1 antibodies accumulation, promoted tumor‐associated macrophages remodeling to antitumoral status, and increased infiltration of dendritic cells and cytotoxic T lymphocytes, resulting in more favorable treatment effect compared to those of free antibodies. Additionally, NCPA also shows less IRAEs, including anemia, pneumonia, hepatitis, and small intestinal inflammation in vivo. Altogether, a potent dual checkpoint blockade immunotherapy utilizing NCPA with enhanced antitumor immunity and reduced IRAEs is demonstrated. [ABSTRACT FROM AUTHOR]

Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics. The newly emerging role of nitric oxide (NO) to conquer drug resistance has been recognized as a potential strategy. However, it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites. Herein, we developed a PEGylated indocyanine green (mPEG-ICG) integrated nanovesicle system (PIDA) to simultaneously load doxorubicin hydrochloride (DOX⋅HCl) and the NO donor L-arginine (L-Arg), which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers. Upon 808 nm irradiation, the NO released from PIDA led to a decrease in mitochondrial membrane potential, an increase in ROS and significant ATP depletion in K562/ADR cells, thus inhibiting cell growth and resolving the problem of drug resistance. Consequently, the in vivo experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8%. Above all, PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment for their unprecedented clinical efficacy. Signal regulatory protein α (SIRPα) is a phagocytic checkpoint expressed on macrophages, dendritic cells, and other myeloid cells. Cancer cells inhibit macrophage phagocytosis through the interaction of the CD47−SIRPα axis. Disrupting the CD47−SIRPα axis has therefore been a promising strategy in restoring the immune attack against cancer. Herein, we engineered cellular membrane nanovesicles (NVs) presenting SIRPα receptors for phagocytosis checkpoint blockade to augment the antitumor immune response. Furthermore, zebularine (Zeb), an inhibitor of DNA methyltransferase, was encapsulated into SIRPα NVs to reprogram the immunosuppressive tumor microenvironment together with blockade of phagocytosis checkpoint. It is demonstrated that SIRPα@Zeb can improve tumor immunogenicity, the polarization of tumor-associated macrophages to the M1 phenotype, and increase the infiltration of CD8+ T lymphocytes in tumors. The robust antitumor immune response induced by SIRPα@Zeb significantly suppressed tumor growth and extended mice-bearing melanoma xenograft survival. [ABSTRACT FROM AUTHOR]

[Display omitted] Endothelial cell (EC) injury plays a key role in the chronic wound process. A long-term hypoxic microenvironment hinders the vascularization of ECs, thus delaying wound healing. In this study, CX3CL1-functionalized apoptotic body nanovesicles (nABs) were constructed. The "Find-eat" strategy was implemented through a receptor-ligand combination to target ECs that highly express CX3CR1 in the hypoxic microenvironment, therefore amplifying the "Find-eat" signal and promoting angiogenesis. Apoptotic bodies (ABs) were obtained by chemically inducing apoptosis of adipose-derived stem cells (ADSCs), and then functionalized nABs containing deferoxamine (DFO-nABs) were obtained through a series of steps, including optimized hypotonic treatment, mild ultrasound, drug mixing and extrusion treatment. In vitro experiments showed that nABs had good biocompatibility and an effective "Find-eat" signal via CX3CL1/CX3CR1 to induce ECs in the hypoxic microenvironment, thereby promoting cell proliferation, cell migration, and tube formation. In vivo experiments showed that nABs could promote the rapid closure of wounds, release the "Find-eat" signal to target ECs and realize the sustained release of angiogenic drugs to promote new blood vessel formation in diabetic wounds. These receptor-functionalized nABs, which can target ECs by releasing dual signals and achieve the sustained release of angiogenic drugs, may provide a novel strategy for chronic diabetic wound healing. [ABSTRACT FROM AUTHOR]

Treatments for lung adenocarcinoma, a type of non-small-cell lung cancer that accounts for about 40% of all lung cancers, are generally administered intravenously, thus causing systemic side effects and poor pulmonary delivery. Inhalation therapy has been investigated to overcome these limitations; however, it shows limited delivery of drugs to the distal lung region, rapid clearance by alveolar macrophages, and immune responses due to synthetic materials. In this study, we developed inhalable nanotherapeutics to treat lung adenocarcinoma using exogenous pulmonary surfactant (PS) that are lipid-based, clinically used, and easy to fuse with the endogenous PS layer in the alveolar space. We prepared PS-based nanovesicles (PSNVs) using the thin-film hydration method followed by extrusion. PSNVs interacted selectively with alveolar type II cell-derived adenocarcinoma cells in vitro and retained long in the alveolar space of mice after inhalation, presumably due to the incorporated PS proteins. Furthermore, inhalation treatments of paclitaxel-loaded PSNVs significantly inhibited the tumor growth in the lungs of the orthotopic lung cancer mouse model established by intratracheally injection of A549 cells into nude mice, compared with free paclitaxel and paclitaxel-loaded synthetic NVs. These results suggest that the use of PSNVs for inhalation delivery of a wide range of therapeutic agents has great potential for the treatment of various lung diseases, including lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

The brain‐targeted delivery of therapeutic oligonucleotides has been investigated as a new treatment modality for various brain diseases, such as brain tumors. However, delivery efficiency into the brain has been limited due to the blood–brain barrier. In this research, brain‐targeted exosome‐mimetic cell membrane nanovesicles (CMNVs) were designed to enhance the delivery of therapeutic oligonucleotides into the brain. First, CMNVs were produced by extrusion with isolated C6 cell membrane fragments. Then, CMNVs were decorated with cholesterol‐linked T7 peptides as a targeting ligand by hydrophobic interaction, producing T7‐CMNV. T7‐CMNV was in aqueous solution maintained its nanoparticle size for over 21 days. The targeting and delivery effects of T7‐CMNVs were evaluated in an orthotopic glioblastoma animal model. 2′‐O‐metyl and cholesterol‐TEG modified anti‐microRNA‐21 oligonucleotides (AMO21c) were loaded into T7‐CMNVs, and biodistribution experiments indicated that T7‐CMNVs delivered AMO21c more efficiently into the brain than CMNVs, scrambled T7‐CMNVs, lipofectamine, and naked AMO21c after systemic administration. In addition, AMO21c down‐regulated miRNA‐21 (miR‐21) levels in glioblastoma tissue most efficiently in the T7‐CMNVs group. This enhanced suppression of miR‐21 resulted in the up‐regulation of PDCD4 and PTEN. Eventually, brain tumor size was reduced in the T7‐CMNVs group more efficiently than in the other control groups. With stability, low toxicity, and targeting efficiency, T7‐CMNVs may be useful to the development of oligonucleotide therapy for brain tumors. [ABSTRACT FROM AUTHOR]

One of the current concerns to human health is antibiotic resistance, which promotes the use of antibiotics that are more harmful, expensive, and ineffective. In this condition, researchers are turning to innovative options to combat this alarming situation. Combining herbal medicine with nanotechnology has created a new strategy to increase the effectiveness of phytochemical compounds in overcoming antimicrobial resistance. Pistacia atlantica is one of the promising herbs with medicinal benefits, but its poor solubility in biological fluids is challenging. In this regard, we seek to evaluate the antibacterial efficacy of Pistacia atlantica extract-loaded nanovesicle. Cholesterol, Span 40, and Pluronic F127 modified nanoformulation was developed using an environmentally friendly improved heating technique, and it was evaluated for size distribution, zeta potential, morphology, entrapment efficiency (EE%), release behavior, stability, and antimicrobial performance. By using DLS, spherical nanovesicles were identified with a size distribution of 50–150 nm and a zeta potential of −43 mV. The extract's encapsulation efficiency was 72.03%. The developed loaded nanovesicles demonstrated controlled extract release in the tested 96 h and storage stability of at least 12 months at 25 °C. Also, Comparing the two samples, the encapsulated extract had greater antibacterial activity against Candida albicans, Staphylococcus aureus, and Pseudomonas plecoglossicida with MIC of 1320, 570, and 1100 µg/mL, respectively. Besides reducing the misuse of antibiotics by allowing for the controlled release of drugs made from natural sources, we expect the findings described here to help provide alternative plant-based formulations with greater stability and antibacterial activity.

Abstract The brain‐targeted delivery of therapeutic oligonucleotides has been investigated as a new treatment modality for various brain diseases, such as brain tumors. However, delivery efficiency into the brain has been limited due to the blood–brain barrier. In this research, brain‐targeted exosome‐mimetic cell membrane nanovesicles (CMNVs) were designed to enhance the delivery of therapeutic oligonucleotides into the brain. First, CMNVs were produced by extrusion with isolated C6 cell membrane fragments. Then, CMNVs were decorated with cholesterol‐linked T7 peptides as a targeting ligand by hydrophobic interaction, producing T7‐CMNV. T7‐CMNV was in aqueous solution maintained its nanoparticle size for over 21 days. The targeting and delivery effects of T7‐CMNVs were evaluated in an orthotopic glioblastoma animal model. 2′‐O‐metyl and cholesterol‐TEG modified anti‐microRNA‐21 oligonucleotides (AMO21c) were loaded into T7‐CMNVs, and biodistribution experiments indicated that T7‐CMNVs delivered AMO21c more efficiently into the brain than CMNVs, scrambled T7‐CMNVs, lipofectamine, and naked AMO21c after systemic administration. In addition, AMO21c down‐regulated miRNA‐21 (miR‐21) levels in glioblastoma tissue most efficiently in the T7‐CMNVs group. This enhanced suppression of miR‐21 resulted in the up‐regulation of PDCD4 and PTEN. Eventually, brain tumor size was reduced in the T7‐CMNVs group more efficiently than in the other control groups. With stability, low toxicity, and targeting efficiency, T7‐CMNVs may be useful to the development of oligonucleotide therapy for brain tumors.

[Display omitted] • Nanovesicle-templated nanogel PCG is built to efficiently co-load Fe3+ and DHA. • PCG-Fe/DHA achieves dual responsive intracellular release of Fe3+ and DHA. • Fe3+ and DHA in PCG cooperatively disrupt iron homeostasis to enhance ferroptosis. • PCG-Fe/DHA significantly inhibits 4T1 breast tumor growth in vivo. • Fe3+ in PCG produces higher MRI signal intensity for in vivo tumor diagnosis. Ferroptosis is an emerging form of cell death resulting from iron-dependent massive accumulation of lipid peroxides (LPOs). Efficient iron delivery and powerful iron homeostasis disruption remain quite challenging. Herein, we designed a nanovesicle-templated nanogel PCG-Fe/DHA facilitated by the self-assembly of amphiphilic polyphosphazene and the in situ coordination of gallic acid-modified chito-oligosaccharide with Fe3+ to co-deliver iron and dihydroartemisinin (DHA) for ferroptosis cancer therapy. PCG-Fe/DHA exhibited excellent capability of dual drug loading as well as pH-responsive Fe3+ release and esterase-responsive DHA release. The concurrent delivery of Fe3+ and DHA synergistically disrupted intracellular iron homeostasis via the supplementation of exogenous Fe3+ and DHA-induced ferritin degradation, resulting in a surge in the intracellular labile iron pool to initiate the Fenton reaction. Meanwhile, the intracellular redox homeostasis was disrupted due to the decline of glutathione peroxidase 4 (GPX4) abundance by Fe3+-depleting glutathione (GSH). As a result, the intracellular ROS and LPOs were distinctly accumulated, which consequently enhanced ferroptosis of tumor cells. After intravenous injection of PCG-Fe/DHA, the tumor inhibition ratio in 4T1 breast tumor-bearing mice achieved 76.8 %. In addition, the PCG-Fe/DHA nanogel could target tumor and produce 2.4 times higher magnetic resonance imaging (MRI) signal intensity than free Fe. These evidences indicated that PCG-Fe/DHA platform could provide a dual-modal strategy for ferroptosis cancer therapy and MRI-guided tumor diagnosis. [ABSTRACT FROM AUTHOR]

Exosomes are nano-sized biological extracellular vesicles transmitting information between cells and constituting a new intercellular communication mode. Exosomes have many advantages as an ideal drug delivery nanocarrier, including good biocompatibility, permeability, low toxicity, and low immunogenicity. Recently, exosomes have been used to deliver chemotherapeutic agents, natural drugs, nucleic acid drugs, and other antitumor drugs to treat many types of tumors. Due to the limited production of exosomes, synthetic exosome-mimics have been developed as an ideal platform for drug delivery. This review summarizes recent advances in the application of exosomes and exosome-mimics delivering therapeutic drugs in treating cancers. [ABSTRACT FROM AUTHOR]

Cancer is increasingly being recognized as a global health issue with considerable unmet medical need. Despite the rapid progression of anticancer pharmaceuticals, there are still significant challenges for the effective management of cancer. In many circumstances, cancer cells are difficult to detect and treat. Combination of nanovesicles (NVs) and magnetic nanoparticles (MNPs), referred as magnetic nanovesicles (MNVs), is now well recognized as a potential theranostic option for improving cancer treatment outcomes and reducing adverse effects. MNVs can be used for monitoring the long-term fate and functional benefits of cancer therapy. Moreover, MNV-mediated hyperthermia mechanism has been explored as a potential technique for triggering cancer cell death, and/or controlled release of laden cargo. In this review, we focus on the unique characteristics of MNVs as a promising avenue for targeted drug delivery, diagnosis, and treatments of cancer or tumor. Moreover, we discuss critical considerations related to the issues raised in this area, which will guide future research toward better anti-cancer therapeutics for clinical applications.

Wound healing is often impaired in patients with diabetes. Mesenchymal stem cells (MSCs) and MSCs-derived nanovesicles (MNVs) hold promise as therapeutic agents for managing diabetic wounds. However, efficient delivery and controlled release of MNVs within these wounds are essential for maximizing therapeutic effectiveness. In this study, we developed a dual-responsive hydrogel designed to respond to elevated levels of glucose and reactive oxygen species. This hydrogel combines polyvinyl alcohol with phenylboronic acid-grafted chitosan, referred to as PBA-CP, while MNVs were produced by shearing MSCs through membranes with varying pore sizes. The composite PBA-CP/MNVs hydrogel significantly accelerated wound healing in a diabetic wound model by promoting epithelialization, dermal reconstruction, hair follicle formation, and angiogenesis. MNVs were readily taken up by keratinocytes, fibroblasts, and endothelial cells, stimulating their proliferation and migration. Altogether, the chitosan-based PBA-CP/MNVs composite hydrogel presents a promising therapeutic strategy for diabetic wound treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The implementation of chemoradiation combinations has gained great momentum in clinical practices. However, the full utility of this paradigm is often restricted by the discordant tempos of action of chemotherapy and radiotherapy. Here, a gold nanoparticle-based radiation-responsive nanovesicle system loaded with cisplatin and veliparib, denoted as CV-Au NVs, is developed to augment the concurrent chemoradiation effect in a spatiotemporally controllable manner of drug release. Upon irradiation, the in situ generation of •OH induces the oxidation of polyphenylene sulfide from being hydrophobic to hydrophilic, resulting in the disintegration of the nanovesicles and the rapid release of the entrapped cisplatin and veliparib (the poly ADP-ribose polymerase (PARP) inhibitor). Cisplatin-induced DNA damage and the impairment of the DNA repair mechanism mediated by veliparib synergistically elicit potent pro-apoptotic effects. In vivo studies suggest that one-dose injection of the CV-Au NVs and one-time X-ray irradiation paradigm effectively inhibit tumor growth in the A549 lung cancer model. This study provides new insight into designing nanomedicine platforms in chemoradiation therapy from a vantage point of synergizing both chemotherapy and radiation therapy in a spatiotemporally concurrent manner., (© 2024 Wiley‐VCH GmbH.)

Photodynamic therapy (PDT)-based cancer vaccines are shown to be more effective modalities for treating cancer in animal models compared to other methods used to generate cancer cell-derived vaccines. The higher efficacy seems to stem from the generation of cell membrane nanovesicles or fragments that carry both cancer cell-specific antigens and high surface content of damage-associated molecular pattern (DAMP) molecules induced by oxidative stress. To develop more effective cancer vaccines in this direction, we explored the generation of cancer vaccines by applying different sources of oxidative stress on cancer cell cultures followed by spontaneous release or filter extrusions to produce cancer cell-derived DAMP-expressing nanovesicles. Through an in-vitro test based on the co-culture of cancer cells and macrophages, it was found that the nanovesicle vaccines generated by H 2 O 2 are as effective as those generated by PDT in diminishing cancer cell culture masses, providing a simpler way to manufacture vaccines. In addition, the nanovesicle vaccines produced by filter extrusion are as potent as those produced by spontaneous release, rendering a more stable way for vaccine production. [ABSTRACT FROM AUTHOR]

The goal of this study was to develop a bilosomal gel formulation to enhance transdermal permeability of dronedarone hyrdrochloride (DRN) which suffers from poor oral absorption and limited bioavailability. To overcome this obstacle, bilosomes were successfully prepared using 23 full-factorial design. Span®40, cholesterol, sodium deoxycholate (bile salt), clove oil (permeability enhancer), and either Tween® 60 or Tween® 80 (edge activator) were used in bilosome preparation by ethanol injection method. In this design, independent variables were X1, edge activator type; X2, edge activator amount (mg); and X3, permeability enhancer concentration (% w/v). Optimal formula (B2) of the highest desirability of (0.776) demonstrated minimum vesicle size (VS) of 312.4 ± 24.42 nm, maximum absolute value of zeta potential (ZP) − 36.17 ± 2.57 mV, maximum entrapment efficiency (EE %) of 80.95 ± 3.01%, maximum deformability Index (DI) of 8.24 ± 1.26 g and maximum drug flux after 12 h (J12) of 21.23 ± 1.54 µg/cm2 h upon ex vivo permeation study. After 12 h, 70.29 ± 6.46% of DRN was released from B2. TEM identification of B2 showed spherical shaped nanosized vesicles which were physically stable for 3 months at different temperatures. B2 was incorporated into carboxymethylcellulose gel base for easiness of dermal application. B2 gel demonstrated good physical properties, non-Newtonian psuedoplastic flow, and enhanced release (57.0 ± 8.68% of DRN compared to only 13.3 ± 1.2% released from drug suspension after 12 h) and enhanced skin permeation. [ABSTRACT FROM AUTHOR]

Extracellular vesicles derived from mammalian cells could be useful carriers for drug delivery systems (DDSs); however, with regard to clinical application, there are several issues to be overcome. Acerola (Malpighia emarginata DC.) is a popular health food. In this study, the feasibility of orally administered nucleic acid drug delivery by acerola exosome-like nanoparticles (AELNs) was examined. AELNs were recovered from acerola juice using an affinity column instead of ultracentrifugation. MicroRNA (miRNA) was sufficiently encapsulated in AELNs by 30-min incubation on ice and was protected against RNase, strong acid, and base treatments. The administration of an AELN/miRNA mixture in cells achieved downregulation of the miRNA’s target gene, and this mixture showed cytoplasmic localization. AELNs orally delivered small RNA to the digestive system in vivo. The target gene-suppressing effect in the small intestine and liver peaked 1 day after administration, indicating potential for use as an oral DDS for nucleic acid in the digestive system.

Platelets play a crucial role in the recruitment of neutrophils, mediated by P-selectin, CCL5, and ICAM-2. In this study, we prepared platelet membrane nanovesicles from activated platelets. Whether activated platelet membrane nanovesicles can recruit neutrophils has not been reported, nor has their role in antitumor immunity. The results of SDS-PAGE showed that the platelet membrane nanovesicles retained almost all the proteins of platelets. Western blotting showed that both the activated platelets and the platelet membrane nanovesicles expressed P-selectin, ICAM-2, and CCL5. In vivo results of a mouse model of breast cancer-transplanted tumor showed that tumor volume reduced significantly, Ki-67-positive tumor cells decreased, and TUNEL-positive tumor cells increased in tumors after treatment with activated platelet membrane nanovesicles (aPNs). After treatment with aPNs, not only the number of neutrophils, CD8+, CD4+ T cells, and B cells increased, but also IL-12, TNF-α, and IFN-γ levels elevated significantly in tumor tissues.

Nanotechnology has enabled the delivery of small molecular drugs packaged in nanosized vesicles to the target tissues. Plant-Derived Nanoparticles (PDNPs) are vesicles with natural origin and unique properties. These nanoparticles have several advantages over synthetic exosomes and liposomes. They provide bioavailability and biodistribution of therapeutic agents when delivered into different tissues. These nanoparticles can be modified according to the specificity of their functions in target tissues. When PDNPs are internalized, they can induce stem cells proliferation, reduce colitis injury, activate intrinsic and extrinsic apoptosis pathways, and inhibit tumor growth and progression. These properties make them potential drug delivery systems in targeting diseased tissues, such as inflammatory regions and different cancers. [ABSTRACT FROM AUTHOR]

Wound dressing with the capacities of antioxidation, antiinflammation, and efficient angiogenesis induction is expected for effectively promoting wound healing. Herein, a novel core‐shell hyaluronic acid (HA) microneedle (MN) patch with ferrum‐mesenchymal stem cell‐derived artificial nanovesicles (Fe‐MSC‐NVs) and polydopamine nanoparticles (PDA NPs) encapsulated in the needle tips is presented for wound healing. Fe‐MSC‐NVs containing multifunctional therapeutic cytokines are encapsulated in the inner HA core of the MN tips for accelerating angiogenesis. The PDA NPs are encapsulated in the outer methacrylated hyaluronic acid (HAMA) shell of the MN tips to overcome the adverse impacts from reactive oxygen species (ROS)‐derived oxidative stress. With the gradual degradation of HAMA patch tips in the skin, the PDA NPs are sustainably released at the lesion to suppress the ROS‐induced inflammation reaction, while the Fe‐MSC‐NVs significantly increase the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVEC). More attractively, the combination of PDA NPs and Fe‐MSC‐NVs further promotes M2 macrophage polarization, thereby suppressing wound inflammation. Through in vivo experiment, the Fe‐MSC‐NVs/PDA MN patch shows an excellent effect for diabetic wound healing. These features of antioxidation, antiinflammation, and pro‐angiogenesis indicate the proposed composite core‐shell MN patch is valuable for clinical wound healing applications. [ABSTRACT FROM AUTHOR]

Abstract Wound dressing with the capacities of antioxidation, antiinflammation, and efficient angiogenesis induction is expected for effectively promoting wound healing. Herein, a novel core‐shell hyaluronic acid (HA) microneedle (MN) patch with ferrum‐mesenchymal stem cell‐derived artificial nanovesicles (Fe‐MSC‐NVs) and polydopamine nanoparticles (PDA NPs) encapsulated in the needle tips is presented for wound healing. Fe‐MSC‐NVs containing multifunctional therapeutic cytokines are encapsulated in the inner HA core of the MN tips for accelerating angiogenesis. The PDA NPs are encapsulated in the outer methacrylated hyaluronic acid (HAMA) shell of the MN tips to overcome the adverse impacts from reactive oxygen species (ROS)‐derived oxidative stress. With the gradual degradation of HAMA patch tips in the skin, the PDA NPs are sustainably released at the lesion to suppress the ROS‐induced inflammation reaction, while the Fe‐MSC‐NVs significantly increase the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVEC). More attractively, the combination of PDA NPs and Fe‐MSC‐NVs further promotes M2 macrophage polarization, thereby suppressing wound inflammation. Through in vivo experiment, the Fe‐MSC‐NVs/PDA MN patch shows an excellent effect for diabetic wound healing. These features of antioxidation, antiinflammation, and pro‐angiogenesis indicate the proposed composite core‐shell MN patch is valuable for clinical wound healing applications.

Extracellular vehicles have a natural targeting ability and immune tolerance of being usually applied in drug delivery systems; however, the purification of EVs is complicated and the production yield was quite low. We developed an artificial cellular mimetic nanovesicle (NV) with melanoma fragment membrane for the transportation with curcumin to achieve the anticancer purpose. B16F10 derived NVs were manufactured by the breakdown of cells using a series of extrusions through cut-off size filters (10 and 5 µm), and the whole procedure was easy and time-saving. To terminate the suspicion of cancer metastatic issue, B16F10 cells were treated by 30-min sonication and 1-min UVB exposure to remove genetic materials before the extrusion. B16F10 derived NV loaded with curcumin was called NV(S30U1/Cur), and the anticancer effect was evaluated by cell-based viability, immune, migration, and invasion. The results showed that NVs were manufactured by passing through 10 and 5 µm filters having an enviable production yield, and the mRNA amounts were declined within NVs produced by B16F10 cells treated with UVB in a comparison to the control group. NV(S30U1/Cur) were effectively decreased B1610 cell viability, and migratory and invasive abilities were also reduced significantly. Besides, CD8+ expression of murine primary lymphocytes was activated with CD4+ reduction by NV(S30U1/Cur) to stimulate the inherent tumor suppressive capacity in the immune system. Taken together, we established bioengineered NVs serving as novel cell mimetic nanocarriers to deliver natural compound for malignant melanoma potential immune chemotherapy. Data Availability Statement: The data used to support the findings of this study are available from the corresponding author upon requests.

Docetaxel (DTX) is a highly lipophilic, BCS class IV drug with poor aqueous solubility (12.7 µg/mL). Presently, only injectable formulation is available in the market which uses a large amount of surfactant (Tween 80) and dehydrated alcohol as a solubilizer. High concentrations of Tween 80 in injectable formulations are associated with severe consequences i.e. nephrotoxicity, fluid retention, and hypersensitivity reactions. The present study aims to eliminate Tween 80, thus novel biocompatible surfactant Vitamin E TPGS based nanovesicle formulation of DTX (20 mg/mL) was developed and evaluated for different quality control parameters. Optimized nanovesicular formulation (NV-TPGS-3) showed nanometric size (102.9 ± 2.9 nm), spherical vesicular shape, high drug encapsulation efficiency (95.2 ± 0.5%), sustained-release profile and high dilution integrity with normal saline. In vitro cytotoxicity assay, showed threefold elevation in the IC50 value of the optimized formulation in comparison to the commercial formulation. Further, no mortality and toxicity were observed during 28 days repeated dose sub-acute toxicity studies in Swiss albino mice up to the dose of 138 mg/kg, whereas, commercial formulation showed toxicity at 40 mg/kg. In addition, in vivo anticancer activity on Ehrlich Ascites Carcinoma induced mice showed a significant tumour growth inhibition of 76.3 ± 5.3% with the NV-TPGS-3 treatment when compared to Ehrlich Ascites Carcinoma control. Results demonstrated that the developed Vitamin E TPGS based nanovesicular formulation of DTX could be a better alternative to increase its clinical uses with improved therapeutic efficacy, reduced toxicity and dosing frequency, and sustained drug release behaviour. [ABSTRACT FROM AUTHOR]

Polymeric vesicles served as the most promising candidates of drug delivery nanocarriers are attracting increasing attention in cancer therapy. Significant advantages have been reported, including hydrophilic molecules with high loading capacity, controllable drug release, rapid and smart responses to stimuli and versatile functionalities. In this study, we have made a systematic review of all aspects of nano-vesicles as drug delivery vectors for cancer treatment, mainly including the following aspect: characteristics of polymeric nanovesicles, polymeric nanovesicle synthesis, and recent progress in applying polymeric nanovesicles in antitumor drug delivery. Polymer nanovesicles have the advantages of synergistic photothermal and imaging in improving the anticancer effect. Therefore, we believe that drug carrier of polymer nanovesicles is a key direction for cancer treatment.

Insufficient antigen self-presentation of tumor cells and ineffective antigen cross-presentation by dendritic cells (DCs) contribute to diminished immune recognition and activation, which cause resistance to immunotherapies. Herein, we present an ultrasound-activatable in situ vaccine by utilizing a hybrid nanovesicle composed of a thylakoid (TK)/platelet (PLT) membrane and a liposome encapsulating DNA methyltransferase inhibitor zebularine (Zeb) and sonosensitizer hematoporphyrin monomethyl ether (HMME). Upon local exposure to ultrasound, reactive oxygen species (ROS) are generated and induce the sequential release of the payloads. Zeb can efficiently inhibit tumor DNA hypermethylation, promoting major histocompatibility complex class I (MHC-I) molecules-mediated antigen self-presentation to improve immune recognition. Meanwhile, the catalase on the TK membrane can decompose the tumoral overexpressed H 2 O 2 into O 2 , which boosts the generation of ROS and the destruction of tumor cells, resulting in the in situ antigen release and cross-presentation of tumor antigens by DCs. This in situ vaccine simultaneously promotes antigen self-presentation and cross-presentation, resulting in heightened antitumor immunity to overcome resistance.

Although biomacromolecules are promising cytosolic drugs which have attracted tremendous attention, the major obstacles were the cellular membrane hindering the entrance and the endosome entrapment inducing biomacromolecule degradation. How to avoid those limitations to realize directly cytosolic delivery was still a challenge. Here, we prepared oligoarginine modified lipid to assemble a nanovesicle for biomacromolecules delivery, including mRNA (mRNA) and proteins which could be directly delivered into the cytoplasm of dendritic cells through subendocytosis-mediated membrane fusion. We named this membrane fusion lipid nanovesicle as MF-LNV. The mRNA loaded MF-LNV as nanovaccines showed efficient antigen expression to elicit robust immuno responses for cancer therapy. What's more, the antigen protein loaded MF-LNV as nanovaccines elicits much stronger CD8 + T cell specific responses than lipid nanoparticles through normal uptake pathways. This MF-LNV represented a refreshing strategy for intracellular delivery of the biomacromolecule.

[Display omitted] • EGCG was encapsulated in phospholipid nanovesicles with emulsion-transfer methods. • The addition of γ-cyclodextrin in nanovesicles had better EGCG encapsulation. • Cyclodextrin could improve EGCG sustained releases in phospholipid nanovesicles. • Nanovesicle could prevent the binding of EGCG with mucin and mask its bitterness. A novel phospholipid-based nanovesicle (PBN) was developed to encapsulate (-)-epigallocatechin gallate (EGCG), a major polyphenol in green tea, to mask its bitter taste and expand its application in food products. The PBN was formed using W/O emulsion-transfer methods and showed a multilayer membrane nanovesicle structure (around 200 nm) observed with TEM. The PBN possessed a high encapsulation efficiency (92.1%) for EGCG. The bitterness of EGCG was significantly reduced to 1/12 after encapsulation. Fourier transform infrared spectroscopy (FTIR) indicated the EGCG mainly interacted with the upper chain/glycerol/head group region of the lipid bilayer in PBN. Quartz crystal microbalance with dissipation (QCM-D) showed the addition of γ-cyclodextrin in PBN enhanced EGCG's adsorption with phospholipids and allowed for its good sustained release. Encapsulating EGCG in PBN inhibited its complexation with mucin, reducing bitterness and astringency. This provides a new method to improve EGCG's flavor, potentially expanding its application in the food industry. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT)-based cancer vaccines are shown to be more effective modalities for treating cancer in animal models compared to other methods used to generate cancer cell-derived vaccines. The higher efficacy seems to stem from the generation of cell membrane nanovesicles or fragments that carry both cancer cell-specific antigens and high surface content of damage-associated molecular pattern (DAMP) molecules induced by oxidative stress. To develop more effective cancer vaccines in this direction, we explored the generation of cancer vaccines by applying different sources of oxidative stress on cancer cell cultures followed by spontaneous release or filter extrusions to produce cancer cell-derived DAMP-expressing nanovesicles. Through an in-vitro test based on the co-culture of cancer cells and macrophages, it was found that the nanovesicle vaccines generated by H2O2 are as effective as those generated by PDT in diminishing cancer cell culture masses, providing a simpler way to manufacture vaccines. In addition, the nanovesicle vaccines produced by filter extrusion are as potent as those produced by spontaneous release, rendering a more stable way for vaccine production.

Plant extract compounds have various industrial applications as well as some limitations. However, the encapsulation of them through different techniques is known as a way for optimizing their physicochemical properties, biological activities, and effectivity to improve the shelf-life of different foods. In this review, the latest food applications of cyclodextrin inclusion complexes, liposomes, and electrospinning as encapsulating methods of plant extract compounds were compared. Moreover, all possible combinations of these methods and their application in food research were deeply discussed. Cyclodextrin inclusion complexes have been used to encapsulate hydrophobic compounds, while liposomes and electrospinning allow encapsulating of both, hydrophilic and/or hydrophobic compounds. Furthermore, cyclodextrin itself is a kind of "ready encapsulating (wall) material" that allows the formation of inclusion complexes, while in liposomes and electrospinning the formation of wall material is required. Most reported applications with cyclodextrin inclusion complexes and electrospinning focus mainly on the development of food packaging materials. In contrast, liposomes have been widely used to produce edible films and food coatings. Moreover, the use of cyclodextrin inclusion complexes and liposomes as ingredients has allowed to obtain functional foods with better physicochemical and sensory properties. On the other hand, the double or triple combination of these methods have also been reported, and the key benefits of them have been the improvement of encapsulation parameters and encapsulated compound properties, as well as the prolongation of the shelf-life of foods where the encapsulated compound (through combining methods) was applied. Image 1 • The three encapsulating methods and their combinations were compared. • Combination of methods have allowed to prolong the food shelf-life. • The combination liposomes and cyclodextrin improve the EE and prolonged release. • Electrospun fibers act as support of inclusion complexes and/or liposomes. • The applications of encapsulating methods in real food matrices were described. [ABSTRACT FROM AUTHOR]

Introduction: Central nervous system (CNS)-related disorders are increasingly being recognized as a global health challenge worldwide. There are significant challenges for effective diagnosis and treatment due to the presence of the CNS barriers which impede the management of neurological diseases. Combination of nanovesicles (NVs) and magnetic nanoparticles (MNPs), referred to as magnetic nanovesicles (MNVs), is now well suggested as a potential theranostic option for improving the management of neurological disorders with increased targeting efficiency and minimized side effects., Areas Covered: This review provides a summary of major CNS disorders and the physical barriers limiting the access of imaging/therapeutic agents to the CNS environment. A special focus on the unique features of MNPs and NV is discussed which make them attractive candidates for neuro-nanomedicine. Furthermore, a deeper understanding of MNVs as a promising combined strategy for diagnostic and/or therapeutic purposes in neurological disorders is provided., Expert Opinion: The multifunctionality of MNVs offers the ability to overcome the CNS barriers and can be used to monitor the effectiveness of treatment. The insights provided will guide future research toward better outcomes and facilitate the development of next-generation, innovative treatments for CNS disorders.

Lipid nanovesicles (NVs) are the first nanoformulation that entered the clinical use in oncology for the treatment of solid tumors. They are indeed versatile systems which can be loaded with either hydrophobic or hydrophilic molecules, for both imaging and drug delivery, and with high biocompatibility, and limited immunogenicity. In the present work, NVs with a lipid composition resembling that of natural vesicles were prepared using the ultrasonication method. The NVs were successfully loaded with fluorophores molecules (DOP-F-DS and a fluorescent protein), inorganic nanoparticles (quantum dots and magnetic nanoparticles), and anti-cancer drugs (SN-38 and doxorubicin). The encapsulation of such different molecules showed the versatility of the developed systems. The size of the vesicles varied from 100 up to 300 nm depending on the type of loaded species, which were accommodated either into the lipid bilayer or into the aqueous core according to their hydrophobic or hydrophilic nature. Viability assays were performed on cellular models of breast cancer (MCF-7 and MDA-MB-231). Results showed that NVs with encapsulated both drugs simultaneously led to a significant reduction of the cellular activity (up to 22%) compared to the free drugs or to the NVs encapsulated with only one drug. Lipidomic analysis suggested that the mechanism of action of the drugs is the same, whether they are free or encapsulated, but administration of the drugs by means of nanovesicles is more efficient in inducing cellular damage, likely because of a quicker internalization and a sustained release. This study confirms the versatility and the potential of lipid NVs for cancer treatment, as well as the validity of the ultrasound preparation method for their preparation.

Abstract Background Cilomilast is a phosphodiesterase 4 (PDE4) inhibitor for treating inflammatory lung diseases. This agent has a narrow therapeutic index with significant adverse effects on the nervous system. This study was conducted to entrap cilomilast into PEGylated phosphatidylcholine-rich niosomes (phosphatiosomes) to improve pulmonary delivery via the strong affinity to pulmonary surfactant film. Neutrophils were used as a cell model to test the anti-inflammatory activity of phosphatiosomes. In an in vivo approach, mice were given lipopolysaccharide to produce acute lung injury. The surface charge in phosphatiosomes that influenced the anti-inflammatory potency is discussed in this study. Results The average diameter of the phosphatiosomes was about 100 nm. The zeta potential of anionic and cationic nanovesicles was − 35 and 32 mV, respectively. Cilomilast in both its free and nanocapsulated forms inhibited superoxide anion production but not elastase release in activated neutrophils. Cationic phosphatiosomes mitigated calcium mobilization far more effectively than the free drug. In vivo biodistribution evaluated by organ imaging demonstrated a 2-fold ameliorated lung uptake after dye encapsulation into the phosphatiosomes. The lung/brain distribution ratio increased from 3 to 11 after nanocarrier loading. The intravenous nanocarriers deactivated the neutrophils in ALI, resulting in the elimination of hemorrhage and alveolar wall damage. Only cationic phosphatiosomes could significantly suppress IL-1β and TNF-α in the inflamed lung tissue. Conclusions These results suggest that phosphatiosomes should further be investigated as a potential nanocarrier for the treatment of pulmonary inflammation.

Cardiovascular disease is a major cause of mortality and morbidity worldwide. Exosome therapies are promising for cardiac repair. Exosomes transfer cargo between cells, have high uptake by native cells and are ideal natural carriers for proteins and nucleic acids. Despite their proreparative potential, exosome production is dependent on parent cell state with typically low yields and cargo variability. Therefore, there is potential value in engineering exosomes to maximize their benefits by delivering customized, potent cargo for cardiovascular disease. Here, we outline several methods of exosome engineering focusing on three important aspects: optimizing cargo, homing to target tissue and minimizing clearance. Finally, we put these methods in context of the cardiac field and discuss the future potential of vesicle design. [ABSTRACT FROM AUTHOR]

Background: It has been reported that during the culture of human placental explants, the syncytiotrophoblast dies between 3 and 24 h and is then replaced within 48 h by a new syncytiotrophoblast layer formed by the fusion of underlying cytotrophoblasts. Most frequently the death of the syncytiotrophoblast is indicated by the uptake of nuclear stains such as propidium iodide (PI). This process is reportedly similar in both early and late gestation placental explants.Methods: We cultured first trimester placental explants for up to 48 h and tested membrane intactness by exposure to PI. Connexin and pannexin mRNAs were quantified by RT-PCR and protein levels determined by immunofluorescence. The syncytiotrophoblast membrane leak was determined by culturing explants in the presence of hemichannel blockers. Extrusion of extracellular vesicles from the syncytiotrophoblast was quantified.Results: Nuclei of the syncytiotrophoblast were stained with PI following approximately 4 h of culture and this was prevented by culturing the explants with pannexin-1 blockers. Expression of pannexin-1 hemichannels increased during explant culture (p = 0.0027). Extracellular vesicles were most abundantly extruded from the explants during the first 3 h of culture and the temporal pattern of extrusion was unaltered by blocking hemichannels.Discussion: We show the mechanism of uptake of nuclear non-viability stains into the syncytiotrophoblast during explant culture is via upregulation of pannexin 1 hemichannels. Contrary to suggestions by some, the production of extracellular vesicles from cultured placental explants is not an in vitro artefact resulting from the apparent death of the syncytiotrophoblast in explant cultures. [ABSTRACT FROM AUTHOR]

Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death. Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges. In the present study, amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine) (mPEG-P(Asp(DBA)-co-Phe)) was synthesized and self-assembled into pH-responsive polymeric vesicle. The vesicle was utilized to co-deliver cancer-associated epidermal growth factor (EGFR) inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride (DOX) for enhanced non-small-cell lung cancer (NSCLC) therapy. As evaluated in vitro, the pH-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis. In addition, in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using pH-sensitive nanovector was a promising strategy for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most malignant breast cancer, with high rates of relapse and metastasis. Because of the nonspecific targeting of chemotherapy and insurmountable aggressiveness, TNBC therapy lacks an effective strategy. Exosomes have been reported as an efficient drug delivery system (DDS). CD82 is a tumor metastasis inhibitory molecule that is enriched in exosomes. Aptamer AS1411 specifically targets TNBC cells due to its high expression of nucleolin. We generated a "triple-punch" cell membrane-derived exosome-mimetic nanovesicle system that integrated with CD82 overexpression, AS1411 conjugation, and doxorubicin (DOX) delivery. CD82 enrichment effectively inhibits the migration of TNBC cells. AS1411 conjugation specifically targets TNBC cells. DOX loading effectively inhibits proliferation and induces apoptosis of TNBC cells. Our results demonstrate a system of exosome-mimetic nanovesicles with "triple-punch" that may facilitate TNBC therapeutics.

In recent years various polymeric vesicles have been reported that show promising results for drug delivery applications, nanomotors and/or nanoreactors. These polymeric vesicles can be assembled from many different materials and various coupling reactions have been applied for functionalization of the vesicles. However, the designs reported are still rather simple, as it is challenging to mimic biological complex systems. In this review we focus on the properties of widely used hydrophobic polymers to better understand polymersome properties for various applications. Examples are shown of how researchers have used and modulated block‐copolymers and their properties to their advantage. Furthermore, an overview of possible end group functionalizations of nanoparticles is reported, giving insight in recent developments of smart nanoparticles for biomedical applications. [ABSTRACT FROM AUTHOR]