Objectives:Resveratrol (Res) is a bifunctional compound found in numerous plants, including
grapes and mulberries. Nanotechnology has promising applications in medicine. The ability
of various nanomaterials to serve as radiosensitizers against tumor cells were reported in several
manuscripts. The present investigation aimed to assess the antitumor and radiosensitizing effects of
Res-CMCNPs on EAC-bearing mice.Methods:Res-CMCNPs have been developed using the CMC emulsification cross-linking technique.
Entrapment efficiency (%), particle size, Polydispersity index and ZETA potential, UV, FTIR
spectra, and drug release were evaluated and described for RES-CMCNPs. The radiosensitizing
properties of RES-CMCNPs were also evaluated in vitro and in vivo against EAC-carrying rodents.
The LD50 of Res-CMCNPs was estimated and its 1/20 LD50 was prepared for treating EAC transplanted
mice.Results:The results revealed that the Res-CMCNPs exhibited a high entrapment efficiency
(85.46%) and a size of approximately 184.60 ±17.36 nm with zeta potential value equals -51.866
mv. Also, the UV spectra of Res and Res-CMCNPs have strong absorption at 225 and 290 nm. The
percentage of resveratrol release at pHs 5.8 and 7.4 was found to be 56.73% and 51.60%, respectively,
after 24 h at 100 rpm. Also, the FTIR analysis confirmed the chemical stability of resveratrol in
Res-CMCNPs cross-linking. The IC50 values of Res-CMCNPs against EAC cells viability were
32.99, 25.46, and 22.21 μg after 24-, 48- and 72 h incubation, respectively, whereas those of Res-
CMCNPs in combination with γ-irradiation after 6-, 10 and 12-mins exposure were 24.07, 16.06 and
7.48 μg, respectively. Also, the LD50 of Res-CMCNPs was 2180 mg/kg.b.w. The treatment of
EAC-bearing mice with Res-CMCNPs plus γ-irradiation improved plasma levels of NO, caspase-3,
P53 and NF-kB levels as well as liver MDA, GSH, SOD, CAT, LT-B4, aromatase, Bax, Bcl2 and
TGF-β levels and exhibited more significant anticancer activity than administration of Res-
CMCNPs and/or exposure to γ-irradiation individually. On the other hand, administration of Res-
CMCNPs in combination with γ-irradiation attenuated liver mRNAs (21, 29b, 181a, and 451) gene
expression.Conclusion:Grafting resveratrol onto carboxymethyl chitosan appears to be a promising strategy
for cancer therapy as a radiosensitizer, potentiating tumor cells' sensitivity to radiation by improving
levels of proinflammatory features and antioxidant biomarkers.