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In recent years, the use of cationic peptides as alternative drugs with anticancer activity has received attention. In this study, the targeted release of curcumin (Cur) and CM11 peptide alone and together against hepatocellular carcinoma (HCC) was evaluated using chitosan nanoparticles (CS NPs) coated with Pres1 that target the SB3 antigen of HCC cells (PreS1-Cur-CM11-CS NPs). SB3 protein is the specific antigen of HCC and the PreS1 peptide is a part of the hepatitis B antigen, which can specifically bind to the SB3 protein. Chitosan was used to prepare NPs. To Cur and CM11 loading, drugs were added to the CS solution in appropriate concentrations. Pres1 was coupled to the surface of the NPs using EDC catalyst to target NPs against HepG2 cells. SEM and DLS analysis confirmed that the PreS1-Cur-CM11-CS NPs had a size of about 132 nm, the ideal size for penetrating the cell membrane. The loading of Cur and CM11 was equal to 87% and 65%, respectively, which had a sustained and better release in the acidic environment than in the physiological environment. The MTT assay showed that PreS1-Cur-CM11-CS NPs act in a targeted and specific manner with the highest toxicity on the HepG2 cells compared to the control by a decrease in viability of about 26% after 48 h based on cell apoptosis. The results showed that PreS1-Cur-CM11-CS NPs are capable of targeted and specific drug release against HepG2 cancer cells and have significant potential to fight this cancer., Competing Interests: Declarations. Ethical approval: The study was confirmed by the Ethics Committee of the Baqiyatullah University of Medical Sciences with approval ID: IR.BMSU.BLC.1402.007. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The effects of guanidinium hydrochloride (GdmCl) on two intrinsically disordered proteins (IDPs) are investigated using simulations of the self-organized polymer-IDP (SOP-IDP) model. The impact of GdmCl is taken into account using the molecular transfer model (MTM). We show that due to the dramatic reduction in the stiffness of the highly charged Prothymosin-α (ProTα) with increasing concentration of GdmCl ([GdmCl]), the radius of gyration ( R g ) decreases sharply until about 1.0 M. Above 1.0 M, ProTα expands, caused by the swelling effect of GdmCl. In contrast, R g of α-Synuclein (αSyn) swells as continuously as [GdmCl] increases, with most of the expansion occurring at concentrations less than 0.2 M. Strikingly, the amplitude of the small-angle X-ray scattering (SAXS) profiles for ProTα increases until [GdmCl] ≈ 1.0 M and decreases beyond 1.0 M. The [GdmCl]-dependent SAXS profiles for αSyn, which has a pronounced bump at small wave vector ( q ∼ 0.5 nm -1 ) at low [GdmCl] (≤0.2 M), monotonically decrease at all values of [GdmCl]. The contrasting behavior predicted by the combination of MTM and SOP-IDP simulations may be qualitatively understood by modeling ProTα as a strongly charged polyelectrolyte with nearly uniform density of charges along the chain contour and αSyn as a nearly neutral polymer, except near the C-terminus, where the uncompensated negatively charged residues are located. The precise predictions for the SAXS profiles as a function of [GdmCl] can be readily tested.