Antiadhesive nanosome elicits role of glycocalyx of tumor cell-derived exosomes in the organotropic cancer metastasis.

Despite emerging importance of tumor cells-derived exosomes in cancer metastasis, the heterogeneity of exosome populations has largely hampered systemic characterization of their molecular composition, biogenesis, and functions. This study communicates a novel method for predicting and targeting pre-metastatic sites based on an exosome model "fluorescent cancer glyconanosomes" displaying N-glycans of cultured tumor cells. Glycoblotting by antiadhesive quantum dots provides a nice tool to shed light on the pivotal functions of the glycocalyx reconstructed from four cancer cell types without bias due to other compositions of exosomes. In vivo imaging revealed that circulation, clearance, and organotropic biodistribution of cancer glyconanosomes in mice depend strongly on cancer cell-type-specific N-glycosylation patterns, the compositions of key glycotypes, particularly dominant abundances of high mannose-type N-glycans and the position-specific sialylation. Notably, organ biodistribution of cancer glyconanosomes is reproducible artificially by mimicking cancer cell-type-specific N-glycosylation patterns, demonstrating that nanosomal glycoblotting method serves as promising tools for predicting and targeting pre-metastatic sites determined by the glycocalyx of extracellular vesicles disseminated from the primary cancer site.

Natural Oral Anticancer Medication in Small Ethanol Nanosomes Coated with a Natural Alkaline Polysaccharide.

Oral medication is the most acceptable therapy to treat chronic diseases. Natural drugs and excipients have unique advantages, such as low cost and high safety. We first investigated modified ethanol nanosomes for tumor treatment via oral administration. We loaded curcumin (CM) into small ethanol nanosomes coated with the natural alkaline polysaccharide chitosan (CCSET) for increased absorption and bioavailability and enhanced efficacy against small cell lung cancer (SCLC). Compared to CM and noncoated ethanol nanosomes, CCSETs exhibited superior physicochemical, in vitro-in vivo kinetic, and absorptive properties and treatment efficacy at the cellular and animal levels. The interaction of CM and serum albumin (the quantitative binding force) was analyzed. The bioavailability of CCSET increased by 11.84-fold and the tumor growth inhibition rate increased markedly compared to CM. We first confirmed the effect of CM on SCLC stem cells, and CCSET greatly enhanced this action. We first reported that CM had an antitumor effect on SCLC at the animal level and that CCSET enhanced this effect. Natural alkaline polysaccharide-coated small ethanol nanosomes delivering natural medicine may be a potential oral anticancer strategy.

Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis.

BACKGROUND: Honokiol has been reported to possess anti-inflammatory and neuroprotective activities. However, the poor aqueous solubility of honokiol limits its clinical application for systemic administration. PURPOSE: This study aims to develop a novel formulation of nanosome-encapsulated honokiol (NHNK) for intravenous therapy against mouse experimental autoimmune encephalomyelitis (EAE) that mimics human multiple sclerosis. METHODS: Nanosomes and NHNK were prepared by using an ultra-high pressure homogenization (UHPH) method. Mice were treated with NHNK or empty nanosomes during the peak phase of EAE symptoms. Symptoms of EAE were monitored and samples of the spinal cord were obtained for histopathological examinations. RESULTS: The stock of NHNK containing honokiol in the nanosome formulation, which showed the structure of single phospholipid bilayer membranes, was well formulated with the particle size of 48.0 ± 0.1 nm and the encapsulation efficiency 58.1 ± 4.2%. Intravenous administration of NHNK ameliorated the severity of EAE accompanied by a significant reduction of demyelination and inflammation in the spinal cord. Furthermore, NHNK decreased the number of IL-6+, Iba-1+TNF +, Iba-1+IL-12 p40+, and CD3+IFN-γ+ cells infiltrating the spinal cord. CONCLUSION: The UHPH method simplified the preparation of NHNK with uniformly distributed nanosize and high encapsulation efficiency. Intravenous administration of NHNK ameliorated the severity of EAE by suppressing the infiltration of activated microglia and Th1 cells into the spinal cord. Collectively, these results suggest that the formulation of NHNK is a prospective therapeutic approach for inflammatory CNS diseases, such as multiple sclerosis.

Noninvasive visualization of early osteoarthritic cartilage using targeted nanosomes in a destabilization of the medial meniscus mouse model.

BACKGROUND: Early stage osteoarthritis (OA) is clinically asymptomatic due to the avascular and the aneural nature of the cartilage tissue. Nevertheless, early detection of cartilage tissue is critical in order to impede the progression of OA. Hence, in order to develop effective preventive therapy for OA, diagnosis in the early stages is necessary. METHODS: To achieve this goal, we have developed targeted, fluorescent nanosomes conjugated with monoclonal anti-type II collagen antibodies (MabCII) for diagnosis of early OA. The MabCII-coated nanosomes (targeted-nanosomes) bind to the damaged cartilage explants in vitro and in vivo in an OA mouse model that mimics early stage OA. The OA mouse model was induced by destabilization of the medial meniscus (DMM) in 9-10 weeks old C57Bl/6 mice. RESULTS: The targeted-nanosomes enhanced the binding specificity to the cartilage tissue according to the severity of damage. CONCLUSION: We show that MabCII-nanosomes can precisely detect early stage OA in the DMM mouse model. Thus, MabCII-nanosomes have the potential to be used as a non-invasive method for diagnosing the early osteoarthritic lesions.

Novel lipidic and bienzymatic nanosomes for efficient delivery and enhanced bioactivity of catalase.

The purpose of this study was to evaluate the improved characteristics of catalase (CAE) when loaded in lipidic and bienzymatic nanosomes. Lipidic and bienzymatic nanosomes containing CAE and uricase (LSCU) were manufactured in two buffer solutions. Their micromorphologies, sizes, zeta potentials, enzymatic activities, kinetic characteristics, and hydrogen peroxide-lowering effects were compared with those of free CAE and lipidic nanosomes containing only CAE (LSC). The structural change and stability mechanism were investigated using fluorescent probes. Compared with free CAE and LSC, LSCU had better physiochemical characteristics and improved in vitro enzymatic activity under different temperatures and pH conditions. In vivo bioavailability and peroxidase activity were also improved. For example, the bioavailability of LSCU was ∼450% greater than that of free CAE, and the time required for LSCU to lower hydrogen peroxide concentrations to a physiologically normal level was almost one-third the time required for free CAE and one-half the time required for LSC. The increased catalytic activity and hydrogen peroxide-lowering capabilities of CAE loaded in LSCU could be ascribed to the favorable conformational changes of CAE and the protection offered by the lipidic and bienzymatic nanosomal biomembrane. Lipidic and bienzymatic nanosomes might be promising nanocarriers for the parenteral delivery of therapeutic enzymes such as CAE.

Future nanomedicine for the diagnosis and treatment of osteoarthritis.

Current treatments for osteoarthritis (OA) are largely palliative until the joints become totally dysfunctional and prosthetic replacement becomes necessary. Effective methods are needed for diagnosing OA and monitoring its progression during its early stages, when the effects of therapeutic drugs or biological agents are most likely to be effective. Theranostic nanosomes and nanoparticles have the potential to noninvasively detect, track and treat the early stages of OA. As articular cartilage does not regenerate once it is degraded, cell-based treatments aided by superparamagnetic iron oxide nanoparticle tracking are attractive future treatment modalities for the later stages of OA progression, when significant cartilage replacement is needed. This article will describe the current and future translational approaches for the detection and noninvasive treatment of degenerative OA.

Novel nanosome delivery system combined with siRNA targeting the antimicrobial gene DFB4: a new approach for psoriasis management?

In a recently published issue of the journal, Bracke et al. demonstrate an impressive improvement in psoriasiform features in allogeneic human skin grafts transplanted onto immune-deficient mice. This improvement was achieved using a novel nanosome (SECosome) as a vehicle for delivering topically applied siRNA to human epidermis. Targeting the gene DFB4 with this delivery system, they prevented translation of the antimicrobial peptide, human ß defensin-2(hBD2), thus normalizing the psoriasiform epidermal phenotype of siRNA/SECosome-treated human skin grafts. This study encourages the exploration of topical gene silencing strategies in dermatology and refocuses our attention on both, the role of hBD2 in psoriasis pathogenesis and the thorny question which animal model reflects human psoriasis most faithfully.