Zinc Oxide Nanoparticles Can Intervene in Radiation-Induced Senescence and Eradicate Residual Tumor Cells

Abstract

Despite recent advancements in tumor therapy, metastasis and tumor relapse remain major complications hindering the complete recovery of many cancer patients. Dormant tumor cells, which reside in the body, possess the ability to re-enter the cell cycle after therapy. This phenomenon has been attributed to therapy-induced senescence. We show that these cells could be targeted by the use of zinc oxide nanoparticles (ZnO NPs). In the present study, the properties of tumor cells after survival of 16 Gy gamma-irradiation were investigated in detail. Analysis of morphological features, proliferation, cell cycle distribution, and protein expression revealed classical hallmarks of senescent cells among the remnant cell mass after irradiation. The observed radiation-induced senescence was associated with the increased ability to withstand further irradiation. Additionally, tumor cells were able to re-enter the cell cycle and proliferate again after weeks. Treatment with ZnO NPs was evaluated as a therapeutical approach to target senescent cells. ZnO NPs were suitable to induce cell death in senescent, irradiation-resistant tumor cells. Our findings underline the pathophysiological relevance of remnant tumor cells that survived first-line radiotherapy. Additionally, we highlight the therapeutic potential of ZnO NPs for targeting senescent tumor cells.

Cellular senescence: a key therapeutic target in aging and diseases

“…B2M nanoMIPs loaded with dasatinib demonstrated selective killing of SnCs over proliferating cells and improved potency over dasatinib alone, minimizing the off-target toxicity of dasatinib ( 116 ). Other kinds of NPs have also been reported, including molybdenum disulfide nanoparticles ( 117 ), zinc oxide nanoparticles ( 118 ), and quercetin surface-functionalized magnetite Fe 3 O 4 nanoparticles ( 119 ). However, they were not functionalized to preferentially target SnCs.…”

Metallic Nanoparticles as Antimicrobials and Radiosensitizers: A Review

“…Furthermore, the ability of cells to regrow within 10-20 days was seen but was reduced after treatment with Zinc-Oxide nanoparticles assumed to attract more therapeutic options for residual senescent cancer cells or oncogenes. [18] dIscussIon Metallic nanoparticles have wide clinical applications such as antimicrobial agents, drug targeting activity, prevention of hospital acquired infections by use of medical devices, etc. Gold and Silver nanoparticles are also extensively used in cosmetic and textile industries.…”