Multifunctional Chitosan-Capped Gold Nanoparticles for enhanced cancer chemo-radiotherapy: An invitro study

Abstract

Over the last decade, chemo-radiotherapy represented a well-established paradigm for cancer treatment. Developing new strategies to promote the therapeutic efficacy while reducing toxic side effects of chemo-radiotherapy is a main research objective in cancer therapy. A promising new oncological strategy for enhancing chemo-radiotherapy against cancer involves the utilization of multifunctional nanoparticles (nanocarriers and radiosensitizers). In this work, Chitosan-Capped Gold Nanoparticles (CS-GNPs) were synthesized and loaded with an anticancer agent, Doxorubicin (CS-GNPs-DOX). The prepared multifunctional nano-formulation acted as nano-radiosensitizer, in addition to being an intrinsic drug delivery system allowing efficient loading and targeting of chemotherapeutics. The therapeutic efficacy of CS-GNPs-DOX was studied by treating breast cancer cells (MCF-7) with CS-GNPs-DOX accompanied by different doses of X-rays (0.5, 1 and 3 Gy) and assessing the cytotoxic effect via neutral red cell viability assay. Further assessment of the therapeutic efficacy was conducted using flowcytometry to measure the induction of apoptosis, while neutral comet assay was carried out to check DNA double strand breaks. Results showed that CS-GNPs-DOX could enhance the chemo-radiotherapeutic effect by significantly decreasing cancer cells viability with increasing DNA double strand breaks and inducing cell necrosis even at a very low radiation dose (0.5 Gy). Interestingly, the developed multifunctional CS-GNPs-DOX provided a synergistic regimen for cancer treatment that effectively delivered DOX to tumor cells and enhanced the radiosensitization activity, thus minimizing conventional radio-therapeutic required doses. Accordingly, CS-GNPs-DOX represents a promising multifunctional nanoparticle for enhancing breast cancer chemo-radiotherapy.

Keywords: Breast cancer; Chemo-radiotherapy; Chitosan; Doxorubicin; Gold nanoparticles; Radiosensitizers.