Tailoring Mesoporous Silica-Coated Silver Nanoparticles and Polyurethane-Doped Films for Enhanced Antimicrobial Applications.

The global increase in multidrug-resistant bacteria poses a challenge to public health and requires the development of new antibacterial materials. In this study, we examined the bactericidal properties of mesoporous silica-coated silver nanoparticles, varying the core sizes (ca. 28 nm and 51 nm). We also investigated gold nanoparticles (ca. 26 nm) coated with mesoporous silica as possible inert metal cores. To investigate the modification of antimicrobial activity after the surface charge change, we used silver nanoparticles with a silver core of 28 nm coated with a mesoporous shell (ca. 16 nm) and functionalized with a terminal amine group. Furthermore, we developed a facile method to create mesoporous silica-coated silver nanoparticles (Ag@mSiO2) doped films using polyurethane (IROGRAN®) as a polymer matrix via solution casting. The antibacterial effects of silver nanoparticles with different core sizes were analyzed against Gram-negative and Gram-positive bacteria relevant to the healthcare and food industry. The results demonstrated that gold nanoparticles were inert, while silver nanoparticles exhibited antibacterial effects against Gram-negative (Escherichia coli and Salmonella enterica subsp. enterica serovar Choleraesuis) and Gram-positive (Bacillus cereus) strains. In particular, the larger Ag@mSiO2 nanoparticles showed a minimum inhibitory concentration (MIC) and a minimum bactericidal concentration (MBC) of 18 µg/mL in the Salmonella strain. Furthermore, upon terminal amine functionalization, reversing the surface charge to positive values, there was a significant increase in the antibacterial activity of the NPs compared to their negative counterparts. Finally, the antimicrobial properties of the nanoparticle-doped polyurethane films revealed a substantial improvement in antibacterial efficacy. This study provides valuable information on the potential of mesoporous silica-coated silver nanoparticles and their applications in fighting multidrug-resistant bacteria, especially in the healthcare and food industries.

Development of New Targeted Nanotherapy Combined with Magneto-Fluorescent Nanoparticles against Colorectal Cancer.

The need for non-invasive therapies capable of conserving drug efficiency and stability while having specific targetability against colorectal cancer (CRC), has made nanoparticles preferable vehicles and principal building blocks for the development of complex and multi-action anti-tumoral approaches. For that purpose, we herein report the production of a combinatory anti-tumoral nanotherapy using the production of a new targeting towards CRC lines. To do so, Magneto-fluorescent NANO3 nanoparticles were used as nanocarriers for a combination of the drugs doxorubicin (DOX) and ofloxacin (OFLO). NANO3 nanoparticles' surface was modified with two different targeting agents, a newly synthesized (anti-CA IX acetazolamide derivative (AZM-SH)) and a commercially available (anti-epidermal growth factor receptor (EGFR), Cetuximab). The cytotoxicity revealed that only DOX-containing nanosystems showed significant and even competitive cytotoxicity when compared to that of free DOX. Interestingly, surface modification with AZM-SH promoted an increased cellular uptake in the HCT116 cell line, surpassing even those functionalized with Cetuximab. The results show that the new target has high potential to be used as a nanotherapy agent for CRC cells, surpassing commercial targets. As a proof-of-concept, an oral administration form of NANO3 systems was successfully combined with Eudragit® enteric coating and studied under extreme conditions.

Magneto-Fluorescent Mesoporous Nanocarriers for the Dual-Delivery of Ofloxacin and Doxorubicin to Tackle Opportunistic Bacterial Infections in Colorectal Cancer.

Cancer-related opportunistic bacterial infections are one major barrier for successful clinical therapies, often correlated to the production of genotoxic factors and higher cancer incidence. Although dual anticancer and antimicrobial therapies are a growing therapeutic fashion, they still fall short when it comes to specific delivery and local action in in vivo systems. Nanoparticles are seen as potential therapeutic vectors, be it by means of their intrinsic antibacterial properties and effective delivery capacity, or by means of their repeatedly reported modulation and maneuverability. Herein we report on the production of a biocompatible, antimicrobial magneto-fluorescent nanosystem (NANO3) for the delivery of a dual doxorubicin-ofloxacin formulation against cancer-related bacterial infections. The drug delivery capacity, rendered by its mesoporous silica matrix, is confirmed by the high loading capacity and stimuli-driven release of both drugs, with preference for tumor-like acidic media. The pH-dependent emission of its surface fluorescent SiQDs, provides an insight into NANO3 surface behavior and pore availability, with the SiQDs working as pore gates. Hyperthermia induces heat generation to febrile temperatures, doubling drug release. NANO3-loaded systems demonstrate significant antimicrobial activity, specifically after the application of hyperthermia conditions. NANO3 structure and antimicrobial properties confirm their potential use in a future dual anticancer and antimicrobial therapeutical vector, due to their drug loading capacity and their surface availability for further modification with bioactive, targeting species.

Functional Cyanine-Based PVA:PVP Polymers as Antimicrobial Tools toward Food and Health-Care Bacterial Infections.

The rising of multidrug-resistant bacteria and their associated proliferation as harmful microorganisms boosts the creation of new antibacterial surfaces and biomaterials with applications ranging from health to food packing. Herein, low-cost antibacterial PVA:PVP copolymers containing cyanine derivatives (1, 2, and 3) and their respective Cu2+ complexes are successfully obtained and tested against Gram-negative and Gram-positive bacteria. The possible application in food packing is addressed by covering the surface of typical paper mockups with the doped polymers. All dye-doped polymers present a broad-spectrum antibacterial effect against Gram-positive bacteria, especially for Bacillus cereus (B. cereus), Staphylococcus aureus (S. aureus), and methicillin-resistant S. aureus (MRSA) strains, with PVA:PVP@3 and PVA:PVP@3-Cu being the most effective. Moreover, polymers containing cyanine derivatives present interesting inhibition effects against Pseudomonas aeruginosa (P. aeruginosa), where the production of its characteristic blue/green virulent pigment is not observed. Of the coated paper mockups, PVA:PVP:paper@2 and PVA:PVP:paper@2-Cu are most effective against B. cereus and S. aureus, while PVA:PVP:paper@3 and PVA:PVP:paper@3-Cu are most effective against the MRSA strain. In these formulations, direct contact inhibition mechanisms appear to be more significant than diffusional mechanisms, due to cyanine release hindrance, making them very interesting and versatile platforms for medical and food applications.

Validation of a Standard Luminescence Method for the Fast Determination of the Antimicrobial Activity of Nanoparticles in Escherichia coli.

The use of nanoparticles in multiple industries has raised concerned voices about the assessment of their toxicity/antimicrobial activity and the development of standardized handling protocols. Issues emerge during the antimicrobial assaying of multiple cargo, colorimetric, colloidal nanoformulations, as standard protocols often rely on visual evaluations, or optical density (OD) measurements, leading to high variance inhibitory concentrations (MIC). Thus, a fast, luminescence-based assay for the effective assessment of the antimicrobial activity of nanoparticles is herein reported, using the bioluminescence of an in-house E. coli ATCC® 8739TM construct with the pMV306G13 + Lux plasmid (E. coli Lux). The new strain's sensitivity to ofloxacin as a standard antibiotic was confirmed, and the methodology robustness verified against multiple nanoparticles and colorimetric drugs. The reduction of incubation from 24 to only 8 h, and the sole use of luminescence (LUX490) to accurately determine and distinguish MIC50 and MIC90, are two main advantages of the method. By discarding OD measurements, one can avoid turbidity and color interferences when calculating bacterial growth. This approach is an important tool that contributes to the standardization of methods, reducing samples' background interference and focusing on luminescence as a direct probe for bacterial metabolic activity, growth and, most importantly, the correct assessment of nanomaterials' antimicrobial activity.

Ofloxacin@Doxorubicin-Epirubicin functionalized MCM-41 mesoporous silica-based nanocarriers as synergistic drug delivery tools for cancer related bacterial infections.

Mesoporous silica nanoparticles (MNs) emerged as new promising drug-delivery platforms capable to overcome resistance in bacteria. Dual loading of drugs on these nanocarriers, exploiting synergistic interactions between the nanoparticles and the drugs, could be considered as a way to increase the efficacy against resistant bacteria with a positive effect even at very low concentrations. Considering that patients with cancer are highly susceptible to almost any type of bacterial infections, in this work, nanocarriers mesoporous silica-based, MNs and MNs@EPI were synthetized and submitted to single and/or dual loading of antibiotics (ofloxacin - OFLO) and anticancer drugs (Doxorubicin - DOX; Epirubicin - EPI), and investigated regarding their antibacterial activity against Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Enterococcus faecalis and Pseudomonas aeruginosa. Formulations containing ofloxacin such as MNs-OFLO, MNs-EPI + OFLO, MNs-DOX + OFLO and MNs@EPI + OFLO, present antibacterial activity in all bacterial strains tested. All these are more effective in E.coli with MIC and MBC values for MNs-OFLO, MNs-EPI + OFLO and MNs-DOX + OFLO of around 1 and 2 µgnanomaterial/mL, corresponding to ofloxacin concentrations of 0.03, 0.02 and 0.04 µg/mL, respectively. In the cocktail formulations the conjugation of epirubicin with ofloxacin presents a more effective antibacterial activity with more than 3-fold reduction of ofloxacin concentration when comparing to the single ofloxacin system. By far, the most effective synergistic effect was obtained for the system where epirubicin was functionalized at nanoparticles surface (MNs@EPI), where a 40-fold and 33-fold reductions of ofloxacin concentration were obtained, in P. aeruginosa in comparison to the MNs-OFLO and MNs-EPI + OFLO systems, respectively. These effects are shown in all bacterial strains tested, even in strains that have acquired resistance mechanisms, such as MRSA.