Cancer is one of the most common diseases in developed countries. Recently, gene therapy has emerged as a promising approach to cancer treatment and has already entered clinical practice worldwide. RNA interference-based therapy is a promising method for cancer treatment. However, there are a number of limitations that require vectors to deliver therapeutic nucleic acids to target tissues and organs. Active research is currently underway to find highly effective, low-toxic nanomaterials capable of acting as nanocarriers. In this study, we demonstrated for the first time the ability of symmetrical polyamidoamine dendronized thiacalix[4]arenes (PAMAM-calix-dendrimers) to form stable positively charged complexes with siRNAs, protect them from enzymatic degradation, and efficiently deliver gene material to HeLa cells. A distinctive feature of PAMAM-calix-dendrimers was the unusual decrease in hemo- and cytotoxicity with increasing generation, while these compounds did not cause toxic effects at concentrations required for siRNA binding and delivery. A comparative analysis of the efficiency of complex formation of PAMAM-calix-dendrimers and classical PAMAM dendrimers with siRNAs was also performed. The findings may facilitate the creation of novel unique gene delivery systems for cancer nanomedicine development.

This work studies the impact of the electrostatic interaction between analyte molecules and silver nanoparticles (Ag NPs) on the intensity of surface-enhanced Raman scattering (SERS). For this, we fabricated nanostructured plasmonic films by immobilization of Ag NPs on glass plates and functionalized them by a set of differently charged hydrophilic thiols (sodium 2-mercaptoethyl sulfonate, mercaptopropionic acid, 2-mercaptoethanol, 2-(dimethylamino)ethanethiol hydrochloride, and thiocholine) to vary the surface charge of the SERS substrate. We used two oppositely charged porphyrins, cationic copper(II) tetrakis(4-N-methylpyridyl) porphine (CuTMpyP4) and anionic copper(II) 5,10,15,20-tetrakis(4-sulfonatophenyl)porphine (CuTSPP4), with equal charge value and similar structure as model analytes to probe the SERS signal. Our results indicate that the SERS spectrum intensity strongly, up to complete signal disappearance, correlates with the surface charge of the substrate, which tends to be negative. Using the data obtained and our model SERS system, we analyzed the modification of the Ag surface by different reagents (lithium chloride, polyethylenimine, polyhexamethylene guanidine, and multicharged metal ions). Finally, all those surface modifications were tested using a negatively charged oligonucleotide labeled with Black Hole Quencher dye. Only the addition of copper ions into the analyte solution yielded a good SERS signal. Considering the strong interaction of copper ions with the oligonucleotide molecules, we suppose that inversion of the analyte charge played a key role in this case, instead of a change of charge of the substrate surface. Changing the charge of analytes could be a promising way to get clear SERS spectra of negatively charged molecules on Ag SERS-active supports.

Despite a number of serious challenges and limitations in clinical use, drug therapy is considered one of the most common approaches to treating cancer. However, many types of cancer become resistant to antitumor drugs. Modern supramolecular chemistry provides a variety of compounds and materials that can be used to develop targeted drug delivery approaches, thereby enhancing therapeutic efficacy. Dendrimers are one example of such materials. This study presents an approach to creating supramolecular systems based on poly(amidoamine) dendrimers with a thiacalix[4]arene core (PAMAM-calix-dendrimers), capable of binding and delivering 5-fluorouracil (5-Fu). Fluorescence spectroscopy has demonstrated the good binding of 5-Fu by G1–G3 PAMAM-calix-dendrimers (logKa = 3.15–3.62) regardless of the macrocyclic core conformation. Self-assembly of the PAMAM-calix-dendrimers/5-Fu supramolecular systems was studied by dynamic light scattering and transmission electron microscopy. Loading and release of 5-Fu were evaluated by UV-Vis spectroscopy. The encapsulation efficiency and loading capacity increased slightly in the following order: G3-cone G3-paco G3-alt. For all dendrimers studied, 95% release of 5-Fu was observed within 4 h. An in vitro HeLa tumor cell model showed a positive trend (up to 20%) toward overcoming resistance to 5-Fu chemotherapy when G3-alt is used. These results provide proof of concept for using macrocyclic dendrimers to create anticancer drug delivery systems.