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Oncolytic viruses (OVs) are emerging as promising and potential anti-cancer therapeutic agents, not only able to kill cancer cells directly by selective intracellular viral replication, but also to promote an immune response against tumor. Unfortunately, the bioavailability under systemic administration of OVs is limited because of undesired inactivation caused by host immune system and neutralizing antibodies in the bloodstream. To address this issue, a novel hyaluronic acid based redox responsive nanohydrogel was developed in this study as delivery system for OVs, with the aim to protect the OVs following systemic administration. The nanohydrogel was formulated by water in oil (W/O) nanoemulsion method and cross-linked by disulfide bonds derived from the thiol groups of synthesized thiolated hyaluronic acid. One DNA OV Ad[I/PPT-E1A] and one RNA OV Rigvir(R) ECHO-7 were encapsulated into the developed nanohydrogel, respectively, in view of their potential of immunovirotherapy to treat cancers. The nanohydrogels showed particle size of approximately 300-400 nm and negative zeta potential of around -13 mV by dynamic light scattering (DLS). A uniform spherical shape of the nanohydrogel was observed under the scanning electron microscope (SEM) and transmission electron microscope (TEM), especially, the successfully loading of OV into nanohydrogel was revealed by TEM. The crosslinking between the hyaluronic acid chains was confirmed by the appearance of new peak assigned to disulfide bond in Raman spectrum. Furthermore, the redox responsive ability of the nanohydrogel was determined by incubating the nanohydrogel into phosphate buffered saline (PBS) pH 7.4 with 10 mu M or 10 mM glutathione at 37 degrees C which stimulate the normal physiological environment (extracellular) or reductive environment (intracellular or tumoral). The relative turbidity of the sample was real time monitored by DLS which indicated that the nanohydrogel could rapidly degrade within 10 h in the

A redox-responsive nanocarrier is a promising strategy for the intracellular drug release be-cause it protects the payload, prevents its undesirable leakage during extracellular transport, and favors site-specific drug delivery. In this study, we developed a novel redox responsive core-shell structure nanohydrogel prepared by a water in oil nanoemulsion method using two biocompatible synthetic polymers: vinyl sulfonated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-polyethylene glycol-poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) triblock copolymer, and thiolated hyaluronic acid. The influence on the nanohydrogel particle size and distribution of formulation parameters was investigated by a three-level full factorial design to optimize the preparation condi-tions. The surface and core-shell morphology of the nanohydrogel were observed by scanning electron microscope, transmission electron microscopy, and further confirmed by Fourier transform infrared spectroscopy and Raman spectroscopy from the standpoint of chemical composition. The redox-responsive biodegradability of the nanohydrogel in reducing environments was determined using glutathione as reducing agent. A nanohydrogel with particle size around 250 nm and polydispersity index around 0.1 is characterized by a thermosensitive shell which jellifies at body temperature and crosslinks at the interface of a redox-responsive hyaluronic acid core via the Michael addition reaction. The nanohydrogel showed good encapsulation efficiency for model macromolecules of different molecular weight (93% for cytochrome C, 47% for horseradish peroxidase, and 90% for bovine serum albumin), capacity to retain the peroxidase-like enzymatic activity (around 90%) of cytochrome C and horseradish peroxidase, and specific redox-responsive release behavior. Additionally, the nanohydrogel exhibited excellent cytocompatibility and internalization efficiency into macrophages. Therefore, the developed core-shell struc

Tumor-associated macrophages (TAMs) promote cancer growth and metastasis, but their role in tumor development needs to be fully understood due to the dynamic changes of tumor microenvironment (TME). Here, we report an approach to visualize TAMs by optical imaging and by Fluorine-19 (19F) magnetic resonance imaging (MRI) that is largely applied to track immune cells in vivo. TAMs are targeted with PLGA-PEG-mannose nanoparticles (NPs) encapsulating perfluoro-15-crown-5-ether (PFCE) as MRI contrast agent. These particles are preferentially recognized and phagocytized by TAMs that overexpress the mannose receptor (MRC1/CD206). The PLGA-PEG-mannose NPs are not toxic and they were up-taken by macrophages as confirmed by in vitro confocal microscopy. At 48 h after intravenous injection of PLGA-PEG-mannose NPs, 4T1 xenograft mice were imaged and fluorine-19 nuclear magnetic resonance confirmed nanoparticle retention at the tumor site. Because of the lack of 19F background in the body, observed 19F signals are robust and exhibit an excellent degree of specificity. In vivo imaging of TAMs in the TME by 19F MRI opens the possibility for detection of cancer at earlier stage and for prompt therapeutic interventions in solid tumors.

Huge amounts of chitin and chitosans can be found in the biosphere as important constituents of the exoskeleton of many organisms and as waste by worldwide seafood companies. Presently, politicians, environmentalists, and industrialists encourage the use of these marine polysaccharides as a renewable source developed by alternative eco-friendly processes, especially in the production of regular cosmetics. The aim of this review is to outline the physicochemical and biological properties and the different bioextraction methods of chitin and chitosan sources, focusing on enzymatic deproteinization, bacteria fermentation, and enzymatic deacetylation methods. Thanks to their biodegradability, non-toxicity, biocompatibility, and bioactivity, the applications of these marine polymers are widely used in the contemporary manufacturing of biomedical and pharmaceutical products. In the end, advanced cosmetics based on chitin and chitosans are presented, analyzing different therapeutic aspects regarding skin, hair, nail, and oral care. The innovative formulations described can be considered excellent candidates for the prevention and treatment of several diseases associated with different body anatomical sectors.