Nanotechnology is a promising and rapidly developing area in the 21st century, which affects various fields of science: physics, chemistry, biology, engineering, microelectronics, and medicine

Modern oncological and chronic inflammatory diseases require new approaches to drug therapy due to the limited effectiveness and several side effects of traditional drug preparations

Therapeutic peptides have emerged as promising tools in oncology due to their high specificity, favorable safety profile, and capacity to target molecular hallmarks of cancer. Their clinical translation, however, remains limited by poor stability, rapid proteolytic degradation, and inefficient biodistribution. Iron oxide nanoparticles (IONPs) offer a compelling solution to these challenges. Owing to their biocompatibility, magnetic properties, and ability to serve as both drug carriers and imaging agents, IONPs have become a versatile platform for precision nanomedicine. The integration of peptides with IONPs has generated a new class of hybrid systems that combine the biological accuracy of peptide ligands with the multifunctionality of magnetic nanomaterials. Peptide functionalization enables selective tumor targeting and deeper tissue penetration, while the IONP core supports controlled delivery, MRI-based tracking, and activation of therapeutic mechanisms such as magnetic hyperthermia. These hybrids also influence the tumor microenvironment (TME), facilitating stromal remodeling and improved drug accessibility. Importantly, the iron-driven redox chemistry inherent to IONPs can trigger regulated cell death pathways, including ferroptosis and autophagy, inhibiting opportunities to overcome resistance in aggressive or refractory tumors. As advances in peptide engineering, nanotechnology, and artificial intelligence accelerate design and optimization, peptide–IONP conjugates are poised for translational progress. Their combined targeting precision, imaging capability, and therapeutic versatility position them as promising candidates for next-generation cancer theranostics.

A promising strategy for pancreatic cancer therapy involves developing nanocarriers capable of simultaneously delivering various antitumor substances with diverse physicochemical properties, often resulting in synergistic effects. In the present work, novel biocomposites were developed using amphiphilic N-vinylpyrrolidone polymer incorporating bortezomib (BTZ) and modified with either the DR5-selective TRAIL cytokine (DR5-B) or its fusion with the iRGD effector peptide (DR5-B-iRGD), resulting in AmphPVP-BTZ-DR5-B and AmphPVP-BTZ-DR5-B-iRGD formulations. The release of BTZ was most extensive at acidic pH 5.6, mimicking endolysosomal compartments, while at near-neutral pH 7.4 and alkaline pH 8.2 the release was slower and less complete, indicating a smart pH-responsive behavior suitable for triggered release in the tumor microenvironment. Both AmphPVP-BTZ-DR5-B and AmphPVP-BTZ-DR5-B-iRGD significantly inhibited the growth of pancreatic adenocarcinoma cell lines PANC-1, BxPC-3, and MIA PaCa-2 and induced more rapid internalization of the DR5 receptor in MIA PaCa-2 cells than unmodified particles and free DR5-B or DR5-B-iRGD. Importantly, AmphPVP-BTZ-DR5-B-iRGD exhibited a more pronounced DR5 internalization rate and cytotoxic effect than AmphPVP-BTZ-DR5-B owing to the presence of fusion protein with internalizing iRGD peptide. Both biocomposites induced cell death via the apoptotic pathway while exhibiting minimal cytotoxic effects on healthy cells. Therefore, biocomposites incorporating BTZ and functionalized with DR5-selective TRAIL variants DR5-B or DR5-B-iRGD represent a promising avenue for future studies in pancreatic cancer animal models.

BACKGROUND: Nanocarriers based on biocompatible polymers are a promising delivery tool for biologically active substances and drugs, in particular antitumor agents. Curcumin, a polyphenol, is known to possess pleiotropic therapeutic effects, including antitumor activity. The antitumor potential of curcumin has been shown in various tumor types, including ovarian adenocarcinoma. However, its lipophilic properties and very low bioavailability limits its use. Incorporating curcumin into nanocarriers enhances its delivery options and expands its potential as an antitumor agent. AIM: To produce curcumin-loaded polymeric nanoparticles based on amphiphilic poly-N-vinylpyrrolidone derivatives and its copolymers with acrylic acid, explore their accumulation in the tumor cells; evaluate in vitro cytotoxicity in 2D (monolayer cell culture) and 3D (tumor spheroids) models of human ovarian adenocarcinoma. MATERIALS AND METHODS: The polymers of the amphiphilic poly-N-vinylpyrrolidone derivatives and its copolymers with acrylic acid were obtained using radical polymerization. Emulsion method was used to obtain polymeric nanoparticles. Accumulation of nanoparticles in tumor cells was assessed using flow cytometry (for monolayer culture) or fluorimetric analysis (for spheroids). Cytotoxicity was studied in 2D and 3D models obtained of the human ovarian adenocarcinoma cell line OVCAR-3 using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay). RESULTS: The effective accumulation of curcumin-loaded polymeric nanoparticles in both monolayer culture cells and tumor spheroids was demonstrated. Curcumin-loaded nanoparticles exhibited high-level cytotoxicity in the 2D model of human ovarian adenocarcinoma cells OVCAR-3 (IC50 up to 137±9 μg/mL) and a moderate, although significant cytotoxic effect in a 3D in vitro model. Meanwhile, nanoparticles not loaded with curcumin did not show any cytotoxic activity regardless of their composition or of the additional modification, i.e. with the use of maleimide functional groups. CONCLUSION: These data can provide a foundation for further studies to assess the safety and in vivo antitumor activity of curcumin-loaded nanoparticles based on amphiphilic poly-N-vinylpyrrolidone derivatives.