AUTHOR=Afereydoon Saeid , Haghiralsadat Fateme , Hamzian Nima , Shams Ali , Hemati Mahdie , Naghib Seyed Morteza , Shabani Masoud , Zandieh-doulabi Behrouz , Tofighi Davood TITLE=Multifunctional PEGylated Niosomal Nanoparticle-Loaded Herbal Drugs as a Novel Nano-Radiosensitizer and Stimuli-Sensitive Nanocarrier for Synergistic Cancer Therapy JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=Volume 10 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.917368 DOI=10.3389/fbioe.2022.917368 ISSN=2296-4185 ABSTRACT=Today, the efficient treatment for breast cancer is Radiotherapy (R.T.). To overcome the radioresistant property of cancer cells, radiosensitizing agents can be used in combined irradiation as a special place. By accumulating the cells in the G2 phase, curcumin can enhance the radiosensitive phenomenon of cancer cells and decrease cancer cell survival. The encapsulation of curcumin in a niosomal delivery system enhances aqueous solubility and bioavailability, which results in higher radiosensitive activity. This paper studies the enhancement of the radiosensitizing effect of curcumin-loaded nanoniosome when combined with irradiation. We developed PEGylated nanoniosome formulations based on tween 60, cholesterol, DOTAP, and DSPE-PEG (at 70:30:10:5) with 0.5 mg.ml-1 curcumin by thin-film hydration method. Then, we assessed at the point of -, particle size and zeta potential, entrapment efficiency, and drug release. For the cytotoxicity and apoptosis experiments, different doses of irradiation and different concentrations of free curcumin and curcumin-nanoniosome (single or combined treatment with irradiation) were examined on breast cancer cells. The particle size and zeta potential of curcumin-nanoniosome were 117.5 nm and -15.1 mV, respectively. Entrapment efficiency (EE%) and loading capacities were 72.3% and 6.68%, respectively. The drug release during 6 h was 65.9%. Cell survival in the presence of curcumin at the doses of 1 and 3 Gy showed a significant reduction compared to the irradiation at 48 and 72 h(P≤0,000), and also curcumin-containing nanoniosomes significantly increased cytotoxicity and apoptosis with synergistic effect with a combination of irradiation in comparison with free curcumin. The findings indicate that the efficacy of pretreatment with the curcumin-nanoniosome as a radiosensitizer during Radiotherapy enhance irradiation-induced breast cancer cell apoptosis and is a propitious tactic for more effective breast cancer therapy.