Peroxide mediated oxygen delivery in cancer therapy.

Hypoxia is a serious obstacle in cancer treatment. The aberrant vascular network as well as the abnormal extracellular matrix arrangement results in formation of a hypoxic regions in tumors which show high resistance to the curing. Hypoxia makes the cancer treatment challengeable via two mechanisms; first and foremost, hypoxia changes the cell metabolism and leads the cells towards an aggressive and metastatic phenotype and second, hypoxia decreases the efficiency of the various cancer treatment modalities. Most of the cancer treatment methods including chemotherapy, radiotherapy, photodynamic therapy, sonodynamic therapy and immunotherapy are negatively affected by the oxygen deprivation. Therefore, the regional oxygenation is requisite to alleviate the negative impacts of the hypoxia on tumor cells and tumor therapy modalities. A great deal of effort has been put forth to resolve the problem of hypoxia in tumors. Peroxides have gained tremendous attention as oxygen generating components in cancer therapy. The concurrent loading of the peroxides and cancer treatment components into a single delivery system can bring about a multipurpose delivery system and substantially encourage the success of the cancer amelioration. In this review, we have tried to after the description of a relation between hypoxia and cancer treatment modalities, discuss the role of peroxides in tumor hyperoxygenation and cancer therapy success. Thereafter, we have summarized a number of vehicles for the delivery of the peroxide alone or in combination with other therapeutic components for cancer treatment.

Development of an oxygen-releasing electroconductive in-situ crosslinkable hydrogel based on oxidized pectin and grafted gelatin for tissue engineering applications.

Injectable hydrogels with conductivity are highly desirable as scaffolds for the engineering of various electrical stimuli-responsive tissues, including nerve, muscle, retina, and bone. However, oxygen deprivation within scaffolds can lead to failure by causing cell necrosis. Therefore, an oxygen release conductive injectable hydrogel can serve as a promising support for the regeneration of such tissues. In the present study, H2O2-loaded polylactic acid microparticles were fabricated. Then, gelatin-graft-polypyrrole with various pyrrole contents and periodate-oxidized pectin were synthesized, and consequently, injectable conductive hydrogel/microparticle scaffolds, inside which catalase was grafted and trapped, were obtained. The results revealed that spherical particles with a mean diameter of 60.39 µm and encapsulation efficiency of 49.64 %, which persistently provided oxygen up to 14 days, were achieved. Investigations on hydrogels revealed that with the increase of pyrrole content of gelatin-graft-polypyrrole from 0 to 15 %, the swelling ratio, pore size, porosity, and conductivity were increased from 6.5 to 11.8, 173.13 µm-295.96 µm, 79.7%-93.8%, and from 0.06 mS/m to 2.14 mS/m, respectively. On the other hand, the crosslinking degree and compressive modulus of hydrogels were shown to decrease from 67.24%-27.35%, and from 214.1 kPa to 64.4 kPa, respectively. Moreover, all formulations supported cell viability and attachment. Overall, the hydrogel/particle scaffold with the merits of electrical conductivity, injectability, compatibility, and sustained oxygen release can be used as a tissue engineering scaffold, promoting the regeneration of electricity responsive tissues. Considering all the aforementioned characteristics and behavior of the fabricated scaffolds, they may be promising candidates for bone tissue engineering applications.

Oxygen-releasing nanofibers for breathable bone tissue engineering application.

Oxygen is a vital molecule for cell and tissue processes. Electrospun fibers have been extensively used as drug loading carriers due to possibility of well control over drug release with modulating fiber properties. However, they have not been used as depots for oxygen release. In the present study, an oxygen-releasing nanofibrous scaffold has been developed by electrospinning of polylactic acid/nano-calcium peroxide suspension with different polylactic acid concentrations (6.5 and 13% w/v). The electrospun fibers with calcium peroxide cargo provided oxygen content of 30-94 mmHg in a period of 14 days which lies well within the oxygen level of osseous tissue. The release profile of 13% polylactic acid fibers was different with that of 6.5% fibers with respects to the initial content of released oxygen and the release rate. Not only did 13% fibers supply oxygen with a slower rate, but also they resulted in a lower burst release of oxygen. Cell culture studies in hypoxia corroborated that 13% polylactic acid fibers better preserve cell viability comparing 6.5% counterparts as perceived by MTT assay. Moreover, they endowed more favored milieu for adherence, arrangement and migration of mesenchymal stem cells as confirmed by microscopy images. The oxygen-releasing fibers equally affected alkaline phosphatase, osteocalcin, and calcium deposition by mesenchymal stem cells most likely due to interplay between topographical and metabolic cues offered by 6.5 and 13% formulations.

Fabrication of amine-decorated nonspherical microparticles with calcium peroxide cargo for controlled release of oxygen.

Oxygen is an important signaling molecule which affects many behaviors of bone progenitor cells. Oxygen releasing biomaterials depend on their material and design are able to provide and modulate the desired oxygen for cells. To date, many oxygen releasing vehicles have been developed by incorporating microsized calcium peroxide (CPO) into polymeric matrixes. However, an oxygen releasing system based on nano CPO is still lacking. Not only can nanosized CPO provide more controllable oxygen release, but also can be loaded in vehicles of different shapes and sizes. Current research was conducted to take the advantages of nanomaterials as oxygen releasing components. To this end, CPO nanoparticles were synthesized using a hydrolysis-precipitation procedure and then loaded into the poly (lactide-co-glycolide) (PLGA) matrix via an electrospray process. The surface of PLGA/CaO2 particles was decorated with amine functionalities to render them more bioactive through a controlled aminolysis reaction. The studies on PLGA/CaO2 microparticles revealed that biconcave disk-like morphology with a mean diameter of 5.3 µm was formed. The particles persistently provide oxygen content of 35-67.5 mmHg up to 14 days which lies within the acceptable range for bone tissue engineering applications. PLGA/CaO2 microparticles induced 208 and 76% increase in number of viable mesenchymal cells on 6th and 14th days of cell seeding comparing PLGA counterparts. Furthermore, the expression of two bone biomarkers, that is, alkaline phosphatase and osteocalcin, at protein level as well as the extent of calcium deposition was increased in the presence of PLGA/CaO2 microparticles compared to PLGA ones.

Hydrogel/fiber conductive scaffold for bone tissue engineering.

Hydrogel/fiber composites have emerged as compelling scaffolds for regeneration purposes. Any biorelated modification or feature may endow more regenerative functionality to these composites. In the present study, a hydrogel/fiber scaffold possessing electrical conductivity in both phases, hydrogel and fiber, has been prepared and evaluated. Fiber component possessed electrical conductivity due to the presence of polyaniline (PANi) and hydrogel fraction thanks to the presence of graphene nanoparticles. PANi based fibers were processed through electrospinning and transformed into a three-dimensional structure through ultrasonication. The hydrogel precursor solution composed of oxidized polysaccharides, gelatin and graphene with predesigned ratio was added to fibers and left to gel. The results of assessments on pristine hydrogel and hydrogel/fiber denoted that inclusion of conducting fibers into hydrogel increased elastic modulus, roughness and electrical conductivity, whereas decreased hydrophilicity. Moreover, the results showed that hydrogel/fiber composite better supported human osteoblast-like cell adhesion, proliferation, and morphology comparing hydrogel alone. In a nutshell, the presence of gel/fiber architecture along with electrical conductivity may lead the scaffold to be very promising for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 718-724, 2018.