Anti-Tumor Immune Response of Doxorubicin-Conjugated Zinc Oxide Nanoparticles Containing Folic Acid in Breast Cancer Model

Gomaa S, Nassef M, Tabl G, Zaki S and Abdel-Ghany A

Published on: 2023-05-15

Abstract

Purpose: Numerous cancers have been targeted with nanoparticles (NP), but zinc oxide nanoparticles (ZnONP) have potent inhibitory effects against tumors. This study evaluates the anti-tumor immune response of doxorubicin (DOX)-conjugated ZnONP (ZnONP/DOX), folic acid-conjugated ZnONP (ZnONP/FA) and DOX and folic acid-conjugated ZnONP (ZnONP/DOX/FA).

Methods: Herein, the anti-tumor immune responses of ZnONP nanocomposites were evaluated by assessing the splenic lymphocytes CD₄⁺-T cells, CD₈⁺-T cells and natural killer cells (NK) profiles in the tumor models of Ehrlich ascites carcinoma (EAC) tumor cell by detecting their phenotypic expression using flow cytometry in addition to assessing the profile of oxidative stress markers catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA).

Results: As a result, the treatment of cancer-bearing mice with ZnONP/DOX/FA led to high induction of anti-tumor immunity that was cleared by increasing the proliferation rate and the phenotypic expression of lymphocytes CD4⁺-T, CD8⁺-T and NK cells. Additionally, cancer-bearing mice treated with ZnONP/DOX/FA recorded a marked increase in WBC counts, neutrophils relative numbers but obvious decrease in the relative number of lymphocytes, eosinophils and monocytes. Further, ZnONP/DOX/FA conjugates markedly increased the serum level of SOD and CAT that were decreased by EAC tumor cells implantation and obviously decreased the serum level of MDA, enhancing the antioxidant activity to be very close to the naïve mice control.

Coclusion: Consequently, this research offers a hopeful combinatorial approach to induce anti-tumor immunity in malignancies, overcoming chemotherapeutics resistance and decreasing their side effects and more studies are required to connect the biomedical application of this regimen to diagnostic and therapeutic approaches.