Designing of Chitosan Derivatives Nanoparticles with Antiangiogenic Effect for Cancer Therapy

Abstract

Angiogenesis is a physiological process involving the growth of new blood vessels, which provides oxygen and required nutrients for the development of various pathological conditions. In a tumor microenvironment, this process upregulates the growth and proliferation of tumor cells, thus any stage of angiogenesis can be a potential target for cancer therapies. In the present study, chitosan and his derivatives have been used to design novel polymer-based nanoparticles. The therapeutic potential of these newly designed nanoparticles has been evaluated. The antioxidant and MTT assays were performed to know the antioxidant properties and their biocompatibility. The in vivo antiangiogenic properties of the nanoparticles were evaluated by using a chick Chorioallantoic Membrane (CAM) model. The obtained results demonstrate that chitosan derivatives-based nanostructures strongly enhance the therapeutic effect compared to chitosan alone, which also correlates with antitumor activity, demonstrated by the in vitro MTT assay on human epithelial cervical Hep-2 tumor cells. This study opens up new direction for the use of the chitosan derivatives-based nanoparticles for designing of antiangiogenic nanostructured materials, for future cancer therapy.While stimulation of angiogenesis in cancer leads to metastasis, the anti-angiogenic therapy proved to be an important approach against tumor growth. In this respect, it is a well-known fact that the consumption of antioxidants can be recommended to achieve the inhibition of angiogenesis or reversal of unwanted cell-cell adherence [1]. Several studies have been conducted to investigate the connection between antioxidants and pathological angiogenesis, thus leading to mixed conclusions from studies that have been associated with a lower total cancer incidence with the use of antioxidants [2], to studies that have highlighted the lack of any benefit of using antioxidants on the incidence of cancer [3]. All these results are, for certain ones, closely related with the type of antioxidant included in the study (alpha tocopherol, beta-carotene, ascorbic acid) and the investigated tumor location and not least the investigated pharmaceutical formulation. In this context, the use of antioxidants in the form of nanoparticles could improve the efficiency of this therapy due to specific surface area of nanostructures [4], thereby ensuring better contact with cells that would increase the chances of pathological angiogenesis inhibition. However, to have more success in cancer therapy, more studies should be conducted in this direction.Chitosan is a natural cationic polymer exhibits three chemical reactive sites including a primary amine and two primary or secondary hydroxyl groups for further modification [5][6][7]. Nano/microparticles coated with chitosan, synthesized through different techniques for encapsulation (chemical, physical and mechanical techniques), are in continuous development, aiming at the entrapment of bioactive substances, enzymes, hormones, antimicrobial agents, vitamins, mi...

Microvascular Experimentation in the Chick Chorioallantoic Membrane as a Model for Screening Angiogenic Agents including from Gene-Modified Cells

“…Interestingly, anti-angiogenic treatments are frequently seen in literature involve the use of chemical substances, such as the chemotherapy drug doxorubicin [ 129 , 165 ] as well as thalidomide derivatives [ 59 ]. The application of nanoparticles such as gold [ 60 , 84 ], green [ 166 ], zinc tungstate [ 61 ] and chitosan derived nanoparticles [ 94 ] have high efficacy in the inhibition of blood vessel development, with significant reductions in blood vessel number, length and density reported.…”

Chitosan Containing Nano Zn-Organic Framework: Synthesis, Characterization and Biological Activity

“…When lung and colon cancer cell lines were exposed to Zn-BTC@CS for 24, 48, and 72 h, the number of viable cancer cells was reduced, with the most notable effect appearing against colon cancer cell lines ( Figure 5 ). Previous studies declared that chitosan-derivative-based nanostructures showed markedly increased therapeutic impact compared to chitosan alone [ 45 ]. The MTT test showed the toxic effect of Zn-BTC@CS, as it inhibited the proliferation of A549 and DLD-1 cancer cell lines in a dose-dependent manner with IC 50 values of 13.2 and 19.8 µg/mL for the colon and lung cancer cell lines, respectively ( Figure 5 ).…”

The Effect of Chitosan Capped Copper Nanoparticles on Angiogenesis in Cam Assay

“…As a result of the study, they established that copper increases angiogenesis by increasing HIF-1α / VEGF expression [23]. As a result of our literature review about chitosan, we encountered a manuscript by Dragostin et al They demonstrated the anti-angiogenic effect of chitosan nanoparticles in CAM assay [22]. In another study, Ribeiro and colleagues have shown that insulin-containing chitosan nanoparticles stimulate angiogenesis [24].…”

“…Chitosan has been shown to inhibit angiogenesis in chick embryo chorioallantoic membrane (CAM) models [22].…”