The selection of technological parameters for nanoparticle formulation represents a complicated development phase. Therefore, the statistical analysis based on Box–Behnken methodology is widely used to optimize technological processes, including poly(lactic-co-glycolic acid) nanoparticle formulation. In this study, we applied a two-level three-factor design to optimize the preparation of nanoparticles loaded with cobalt (CoTPP), manganese (MnClTPP), and nickel (NiTPP) metalloporphyrins (MeP). The resulting nanoparticles were examined by dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, MTT test, and hemolytic activity assay. The optimized model of nanoparticle formulation was validated, and the obtained nanoparticles possessed a spherical shape and physicochemical characteristics enabling them to deliver MeP in cancer cells. In vitro hemolysis assay revealed high safety of the formulated MeP-loaded nanoparticles. The MeP release demonstrated a biphasic profile and release mechanism via Fick diffusion, according to release exponent values. Formulated MeP-loaded nanoparticles revealed significant antitumor activity and ability to generate reactive oxygen species. MnClTPP- and CoTPP-nanoparticles specifically accumulated in tissues, preventing wide tissue distribution caused by long-term circulation of the hydrophobic drug. Our results suggest that MnClTPP- and CoTPP-nanoparticles represent the greatest potential for utilization in in anticancer therapy due to their effectiveness and safety.

Polyamidoamine (PAMAM) dendrimers of the second generation (G2) are branched polymers containing 16 surface amino groups that allow them to be used as universal carriers on creating systems for drug delivery. G2 labeled with fluorescein isothiocyanate (FITC) efficiently bound with the surface of tumor cells at 4°C and was absorbed by the cells at 37°C. The covalent binding to G2-FITC of a vector protein, a recombinant fragment of the human alpha-fetoprotein receptor-binding domain (rAFP3D), increased the binding and endocytosis efficiency more than threefold. Covalent conjugates of G2 with doxorubicin (Dox) obtained by acid-labile linking of cis-aconitic anhydride (CAA) without the vector protein (G2-Dox) and with the vector protein rAFP3D (rAFP3D-G2-Dox) were accumulated by the tumor cells with high efficiency. However, a selective effect was observed only in rAFP3D-G2-Dox, which also demonstrated high cytotoxic activity against the human ovarian adenocarcinoma SKOV3 cells and low cytotoxicity against human peripheral blood lymphocytes. Based on these results, rAFP3D-G2 conjugate is promising for selective delivery of antitumor drugs.

Metal–organic frameworks (MOFs) are widely used in the biomedical industry. In this study, we developed a new method for obtaining a metal–organic structure of strontium and terephthalic acid, Sr(BDC), and an alternative activation method for removing DMF from the pores. Sr(BDC) MOFs were successfully prepared and characterized by XRD, FTIR, TGA, and SEM. The importance of the activation steps was confirmed by TGA, which showed that the Sr(BDC)(DMF) sample can contain up to a quarter of the solvent (DMF) before activation. In our study, IR spectroscopy confirmed the possibility of removing DMF by ethanol treatment from the Sr-BDC crystals. A comparative analysis of the effect of the activation method on the specific surface and pore size of Sr-BDC and its sorption properties using the model drug doxorubicin showed that due to the undeveloped surface of the Sr-(BDC)(DMF) sample, it is not possible to obtain an adsorption isotherm and determine the pore size distribution, thus showing the importance of the activation step. Cytotoxicity and apoptosis assays were carried out to study the biological activity of MOFs, and we observed relatively low toxicity in the tested concentration range after 48 h, with over 92% cell survival for Sr(BDC)(DMF) and Sr(BDC)(260 °C), with a decrease only in the highest concentration (800 mg L⁻¹). Similar results were observed in our apoptosis assays, as they revealed low apoptotic population generation of 2.52%, 3.23%, and 2.77% for Sr(BDC)(DMF), Sr(BDC) and Sr(BDC)(260 °C), respectively. Overall, the findings indicate that ethanol-activated Sr(BDC) shows potential as a safe and effective material for drug delivery.