Development of chitosan nanoparticles for anticancer drug delivery systems

Chitosan is a natural polymer that is often used in nanotechnology because it has such useful properties as biodegradability and biocompatibility. Chitosan has many benefits, but they are outweighed by drawbacks such insolubility, aggregation at physiological pH, and insufficient cargo release in the cytosol. In order to obtain chitosan nanoparticles that can be used as drug delivery systems, we optimized the synthesis technology by selecting MES buffer pH 6.3 and using a BSA coating step to reduce nanoparticle aggregation. Deposition of the chemotherapeutic agent etoposide in chitosan nanoparticles has been proven and confirmed by IR spectra, although future experiments are needed to tune conditions for stronger interactions. The chitosan nanoparticles that we have obtained can become suitable nanomaterials for biomedical applications as promising carriers for drug delivery

Molecular Mechanisms Governing the Stem Cell’s Fate in Brain Cancer: Factors of Stemness and Quiescence

Cellular quiescence is a reversible, non-cycling state controlled by epigenetic, transcriptional and niche-associated molecular factors. Quiescence is a condition where molecular signaling pathways maintain the poised cell-cycle state whilst enabling rapid cell cycle re-entry. To achieve therapeutic breakthroughs in oncology it is crucial to decipher these molecular mechanisms employed by the cancerous milieu to control, maintain and gear stem cells towards re-activation. Cancer stem-like cells (CSCs) have been extensively studied in most malignancies, including glioma. Here, the aberrant niche activities skew the quiescence/activation equilibrium, leading to rapid tumor relapse after surgery and/or chemotherapy. Unraveling quiescence mechanisms promises to afford prevention of (often multiple) relapses, a key problem in current glioma treatment. This review article covers the current knowledge regarding normal and aberrant cellular quiescence control whilst also exploring how different molecular mechanisms and properties of the neighboring cells can influence the molecular processes behind glioma stem cell quiescence

A Novel C1q Domain-Containing Protein Isolated from the Mollusk Modiolus kurilensis Recognizing Glycans Enriched with Acidic Galactans and Mannans

C1q domain-containing (C1qDC) proteins are a group of biopolymers involved in immune response as pattern recognition receptors (PRRs) in a lectin-like manner. A new protein MkC1qDC from the hemolymph plasma of Modiolus kurilensis bivalve mollusk widespread in the Northwest Pacific was purified. The isolation procedure included ammonium sulfate precipitation followed by affinity chromatography on pectin-Sepharose. The full-length MkC1qDC sequence was assembled using de novo mass-spectrometry peptide sequencing complemented with N-terminal Edman’s degradation, and included 176 amino acid residues with molecular mass of 19 kDa displaying high homology to bivalve C1qDC proteins. MkC1qDC demonstrated antibacterial properties against Gram-negative and Gram-positive strains. MkC1qDC binds to a number of saccharides in Ca(2+)-dependent manner which characterized by structural meta-similarity in acidic group enrichment of galactose and mannose derivatives incorporated in diversified molecular species of glycans. Alginate, κ-carrageenan, fucoidan, and pectin were found to be highly effective inhibitors of MkC1qDC activity. Yeast mannan, lipopolysaccharide (LPS), peptidoglycan (PGN) and mucin showed an inhibitory effect at concentrations three orders of magnitude greater than for the most effective saccharides. MkC1qDC localized to the mussel hemal system and interstitial compartment. Intriguingly, MkC1qDC was found to suppress proliferation of human adenocarcinoma HeLa cells in a dose-dependent manner, indicating to the biomedical potential of MkC1qDC protein

Invertebrate C1q Domain-Containing Proteins: Molecular Structure, Functional Properties and Biomedical Potential

C1q domain-containing proteins (C1qDC proteins) unexpectedly turned out to be widespread molecules among a variety of invertebrates, despite their lack of an integral complement system. Despite the wide distribution in the genomes of various invertebrates, data on the structure and properties of the isolated and characterized C1qDC proteins, which belong to the C1q/TNF superfamily, are sporadic, although they hold great practical potential for the creation of new biotechnologies. This review not only summarizes the current data on the properties of already-isolated or bioengineered C1qDC proteins but also projects further strategies for their study and biomedical application. It has been shown that further broad study of the carbohydrate specificity of the proteins can provide great opportunities, since for many of them only interactions with pathogen-associated molecular patterns (PAMPs) was evaluated and their antimicrobial, antiviral, and fungicidal activities were studied. However, data on the properties of C1qDC proteins, which researchers originally discovered as lectins and therefore studied their fine carbohydrate specificity and antitumor activity, intriguingly show the great potential of this family of proteins for the creation of targeted drug delivery systems, vaccines, and clinical assays for the differential diagnosis of cancer. The ability of invertebrate C1qDC proteins to recognize patterns of aberrant glycosylation of human cell surfaces and interact with mammalian immunoglobulins indicates the great biomedical potential of these molecules

Development of chitosan nanoparticles for anticancer drug delivery systems

Chitosan is a natural polymer that is often used in nanotechnology because it has such useful properties as biodegradability and biocompatibility. Chitosan has many benefits, but they are outweighed by drawbacks such insolubility, aggregation at physiological pH, and insufficient cargo release in the cytosol. In order to obtain chitosan nanoparticles that can be used as drug delivery systems, we optimized the synthesis technology by selecting MES buffer pH 6.3 and using a BSA coating step to reduce nanoparticle aggregation. Deposition of the chemotherapeutic agent etoposide in chitosan nanoparticles has been proven and confirmed by IR spectra, although future experiments are needed to tune conditions for stronger interactions. The chitosan nanoparticles that we have obtained can become suitable nanomaterials for biomedical applications as promising carriers for drug delivery

Development of chitosan nanoparticles for anticancer drug delivery systems

Chitosan is a natural polymer that is often used in nanotechnology because it has such useful properties as biodegradability and biocompatibility. Chitosan has many benefits, but they are outweighed by drawbacks such insolubility, aggregation at physiological pH, and insufficient cargo release in the cytosol. In order to obtain chitosan nanoparticles that can be used as drug delivery systems, we optimized the synthesis technology by selecting MES buffer pH 6.3 and using a BSA coating step to reduce nanoparticle aggregation. Deposition of the chemotherapeutic agent etoposide in chitosan nanoparticles has been proven and confirmed by IR spectra, although future experiments are needed to tune conditions for stronger interactions. The chitosan nanoparticles that we have obtained can become suitable nanomaterials for biomedical applications as promising carriers for drug delivery

Specification of hemocyte subpopulations based on immune-related activities and the production of the agglutinin MkC1qDC in the bivalve Modiolus kurilensis

Bivalves, such as Modiolus are used as indicator organisms to monitor the state of the marine environment. Even though hemocytes are known to play a key role in the adaptive and protective mechanisms of bivalves, these cells are poorly studied in horse-mussel Modiolus kurilensis. In this paper, we present classification of horse-mussel hemocytes based on their immune functions, including the production of specific immune-related molecules, as well as their morphological composition after isolation by density gradient centrifugation. An effective fractionation protocol was adapted to separate four hemocyte subpopulations with distinct morphofunctional profiles. First subpopulation consisted of small under-differentiated hemoblasts (2.20 ± 0.85%) with a bromodeoxyuridine positive nucleus, and did not show any immune reactivity. Second was represented by agranulocytes (24.11 ± 2.40%), with evenly filled cytoplasm containing a well-developed protein-synthesizing apparatus, polysomes, smooth endoplasmic reticulum and mitochondria, and positively stained for myeloperoxidase, acidic proteins, glycogen and neutral polysaccharides. Third subpopulation consisted of eosinophilic granulocytes (62.64 ± 9.32%) that contained the largest number of lysosomes, peroxisomes and vesicles with contents of different density, and showed the highest phosphatase, reactive oxygen species (ROS) and phagocytic activities. Lastly, fourth group, basophilic granulocytes (14.21 ± 0.34%), are main producers of lectin-like protein MkC1qDC, recently discovered in M. kurilensis and characterized by pronounced antibacterial and anticancer activity. These cells characterized by intracytoplasmic of the MkC1qDC localization, forming granule-like bodies visualized with specific antibody. Both granulocytes and agranulocytes showed phagocytic activity and ROS production, and these reactions were more pronounced for eosinophilic granulocytes, suggesting that this group is the key element of the cell-mediated immune response of M. kurilensis. Our results support a concept of bivalve's hemocyte specification with distinct phenotypes

Tumor Microenvironment Modulation by Cancer-Derived Extracellular Vesicles

The tumor microenvironment (TME) plays an important role in the process of tumorigenesis, regulating the growth, metabolism, proliferation, and invasion of cancer cells, as well as contributing to tumor resistance to the conventional chemoradiotherapies. Several types of cells with relatively stable phenotypes have been identified within the TME, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), neutrophils, and natural killer (NK) cells, which have been shown to modulate cancer cell proliferation, metastasis, and interaction with the immune system, thus promoting tumor heterogeneity. Growing evidence suggests that tumor-cell-derived extracellular vesicles (EVs), via the transfer of various molecules (e.g., RNA, proteins, peptides, and lipids), play a pivotal role in the transformation of normal cells in the TME into their tumor-associated protumorigenic counterparts. This review article focuses on the functions of EVs in the modulation of the TME with a view to how exosomes contribute to the transformation of normal cells, as well as their importance for cancer diagnosis and therapy

Newly Woody Artificial Diet Reveals Antibacterial Activity of Hemolymph in Larvae of <i>Zophobas atratus</i> (Fabricius, 1775) (Coleoptera: Tenebrionidae)

The rearing of saproxylic insects in laboratory conditions is an important task for studying the biology of insects. Through understanding nutritional needs, it is possible to optimize beetle rearing in laboratory conditions. In this study, an artificial fungi-based diet (FD) was developed for the cultivation of the darkling beetle Zophobas atratus (Fabricius, 1775) (Coleoptera: Tenebrionidae) in laboratory conditions as a model object for studying the biology of saproxylophagous beetles. To assess the influence of the diet, a number of physiological parameters were measured, including development time, body size, and weight of all stages of the beetle’s life cycle, as well as its immune status. The immune status of Z. atratus was assessed on the basis of larval hemolymph antibacterial activity against six different bacterial strains assessed using disk-diffusion and photometric tests. Our findings show that the FD reduces development time and boosts the immune status as compared to beetles reared on a standard diet (SD). Samples from FD-reared larvae had pronounced antibacterial activity as compared to samples from SD-reared larvae. This work is of fundamental importance for understanding the correlations between nutrition and development of saproxylic Coleoptera and is the first report on immune status regulation in this group of insects