In recent times, many approaches have been developed against drug resistant Gram-negative bacteria. However, low-cost high effective materials which could broaden the spectrum of antibiotics are still needed. In this study, enhancement of linezolid spectrum, normally active against Gram-positive bacteria, was aimed for Gram-negative bacteria growth inhibition. For this purpose, a silica xerogel prepared from a low-cost precursor is used as a drug carrier owing to the advantages of its mesoporous structure, suitable pore and particle size and ultralow density. The silica xerogel is loaded with linezolid and capped with ε-poly-l-lysine. The developed nano-formulation shows a marked antibacterial activity against to Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. In comparison to free linezolid and ε-poly-l-lysine, the material demonstrates a synergistic effect on killing for the three tested bacteria. The results show that silica xerogels can be used as a potential drug carrier and activity enhancer. This strategy could provide the improvement of antibacterial activity spectrum of antibacterial agents like linezolid and could represent a powerful alternative to overcome antibiotic resistance in a near future.

Mesoporous silica nanoparticles (MSNs) are amongst the most used nanoparticles in biomedicine. However, the potentially toxic effects of MSNs have not yet been fully evaluated, being a controversial matter in research. In this study, bare MSNs, PEGylated MSNs (MSNs-PEG), and galacto-oligosaccharide-functionalized MSNs (MSNs-GAL) are synthesized and characterized to assess their genotoxicity and transforming ability on human lung epithelial BEAS-2B cells in short- (48 h) and long-term (8 weeks) exposure scenarios. Initial short-term treatments show a dose-dependent increase in genotoxicity for MSNs-PEG-treated cells but not oxidative DNA damage for MSNs, MSNs-PEG, or for MSNs-GAL. In addition, after 8 weeks of continuous exposure, neither induced genotoxic nor oxidative DNA is observed. Nevertheless, long-term treatment with MSNs-PEG and MSNs-GAL, but not bare MSNs, induces cell transformation features, as evidenced by the cell’s enhanced ability to grow independently of anchorage, to migrate, and to invade. Further, the secretome from cells treated with MSNs and MSNs-GAL, but not MSNs-PEG, shows certain tumor-promoting abilities, increasing the number and size of HeLa cell colonies formed in the indirect soft-agar assay. These results show that MSNs, specifically the functionalized ones, provoke some measurable adverse effects linked to tumorigenesis. These effects are in the order of other nanomaterials, such as carbon nanotubes or cerium dioxide nanoparticles, but they are lower than those provoked by some approved drugs, such as doxorubicin or dexamethasone.

We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of cancer cells with a plasmid controlled by the cytomegalovirus promoter, which promotes β-galactosidase (β-gal) expression from the bacterial gene lacZ (CMV-lacZ). Moreover, dendrimer-like mesoporous silica nanoparticles (DMSNs) are loaded with the prodrug doxorubicin modified with a galactose unit through a self-immolative group (DOXO-Gal) and modified with a disulfide-containing polyethyleneglycol gatekeeper. Once in tumor cells, the reducing environment induces disulfide bond rupture in the gatekeeper with the subsequent DOXO-Gal delivery, which is enzymatically converted by β-gal into the cytotoxic doxorubicin drug, causing cell death. The combined treatment of the pair enzyme/DMSNs-prodrug are more effective in killing cells than the free prodrug DOXO-Gal alone in cells transfected with β-gal.

Background: The use of bioactive molecules isolated from rattlesnake venom and other poisons has been ongoing for years. Among these bioactive compounds present in snake venom, crotoxin (CTX) stands out as a β-heterodimeric neurotoxin isolated from the venom of Crotalus durissus terrificus. Research on this toxin for its applicability to tumor inhibition has advanced to clinical trials in recent years. Consequently, concerns regarding the use of a toxin as a treatment and the search for dose control that does not trigger extreme toxicity have emerged. Thus, it is necessary to investigate alternatives for controlled delivery and targeted toxin administration. Methods: This study aimed to evaluate the in vitro toxic action of CTX and its phospholipase A2 CB (PLA2CB) component, both free and encapsulated in polymeric nanoparticles. The inhibitory concentration value of 50% tumor growth (IC50) for CTX and PLA2CB was determined in an initial screening against six tumor cell lines. After identifying the lowest inhibitory concentration value of 0.8 μM observed in human melanoma (SK-MEL-103), this cell line was chosen. Results: The cell death mechanism triggered by CTX and PLA2CB exhibited characteristics associated with the necrotic process. However, polymeric nanoparticles containing PLA2CB (NP-PLA2CB) demonstrated apoptosis-like cell death processes in flow cytometry. PLGA polymeric nanoparticles containing PLA2CB were synthesized using microfluidics, resulting in NP-PLA2CB with a diameter of 91 ± 2.9 nm and a zeta potential of -21.8 ± 3.2 mV. The encapsulation efficiency of PLA2CB was approximately 70% (protein content). Conclusion: It was concluded that using the phospholipase component of the toxin in a polymeric-controlled delivery and targeted system may be an alternative solution to the issues in advancing this bioactive molecule in clinical-oncological studies. However, further studies are still being conducted for targeted treatment involving this nanotechnological approach.