Designing of Chitosan Derivatives Nanoparticles with Antiangiogenic Effect for Cancer Therapy

Oana-Maria Dragostin,Sangram Keshari Samal,Anca Oancea,Rodica Tatia,Constantin Apetrei,Alexandra Simona Zamfir,Carmen Lăcrămioara Zamfir,Ionuț Dragostin,Elena-Lăcrămioara Lisă

doi:10.3390/nano10040698

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.

Highlights

Angiogenesis is the development of new blood vessels, a process that normally occurs during embryogenesis, wound healing, or uterus function
Several studies have been conducted to investigate the connection between antioxidants and pathological angiogenesis, 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]
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

Summary

Introduction

Angiogenesis is the development of new blood vessels, a process that normally occurs during embryogenesis, wound healing, or uterus function. Several studies have been conducted to investigate the connection between antioxidants and pathological angiogenesis, 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. To have more success in cancer therapy, more studies should be conducted in this direction

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