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.

Time-Dependent Cytotoxic Properties of Terpyridine-Based Copper Complexes.

Five copper complexes supported by terpyridine ligands were prepared and characterized, viz. [Cu3 Cl4 (naphtpy)2 ][CuCl2 ] (1), [Cu2 Cl2 (naphtpy)2 ](ClO4 )2 (2), [CuCl2 (naphtpy)]2 (MeOH)3 (H2 O) (3), [CuCl2 (Cltpy)] (4) and [Cu(Cltpy)2 ](ClO4 )2 (5); (where naphtpy stands for 4'-((naphthalen-2-yl)methoxy)-2,2':6',2''-terpyridine and Cltpy for 4'-chloro-2,2':6',2''-terpyridine). Their ability to interact with DNA was investigated, and their cytotoxic behaviour was examined with three cells lines, namely human ovarian carcinoma cells (A2780), their derived cisplatin-resistant line (A2780cis), and human cervix adenocarcinoma cells (HeLa). All compounds show good cytotoxic properties (especially after 72 h of incubation). Remarkably, two compounds, 4 and 5, are still almost inactive after 24 h (particularly 4), but are highly active after 72 h, with IC50 values in the low-micromolar to sub-micromolar range. Compounds 1 and 2 induce necrosis, whereas late apoptosis is observed with 3-5, 4 exhibiting a behaviour close to that of cisplatin.

Silica Coated Iron/Iron Oxide Nanoparticles as a Nano-Platform for T2 Weighted Magnetic Resonance Imaging.

The growing concern over the toxicity of Gd-based contrast agents used in magnetic resonance imaging (MRI) motivates the search for less toxic and more effective alternatives. Among these alternatives, iron-iron oxide (Fe@FeOx) core-shell architectures have been long recognized as promising MRI contrast agents while limited information on their engineering is available. Here we report the synthesis of 10 nm large Fe@FeOx nanoparticles, their coating with a 11 nm thick layer of dense silica and functionalization by 5 kDa PEG chains to improve their biocompatibility. The nanomaterials obtained have been characterized by a set of complementary techniques such as infra-red and nuclear magnetic resonance spectroscopies, transmission electron microscopy, dynamic light scattering and zetametry, and magnetometry. They display hydrodynamic diameters in the 100 nm range, zetapotential values around -30 mV, and magnetization values higher than the reference contrast agent RESOVIST®. They display no cytotoxicity against 1BR3G and HCT116 cell lines and no hemolytic activity against human red blood cells. Their nuclear magnetic relaxation dispersion (NMRD) profiles are typical for nanomaterials of this size and magnetization. They display high r2 relaxivity values and low r1 leading to enhanced r2/r1 ratios in comparison with RESOVIST®. All these data make them promising contrast agents to detect early stage tumors.

Metal-Organic Framework-Based Antimicrobial Touch Surfaces to Prevent Cross-Contamination.

Infection diseases are a major threat to global public health, with nosocomial infections being of particular concern. In this context, antimicrobial coatings emerge as a promising prophylactic strategy to reduce the transmission of pathogens and control infections. Here, antimicrobial door handle covers to prevent cross-contamination are prepared by incorporating iodine-loaded UiO-66 microparticles into a potentially biodegradable polyurethane polymer (Baycusan eco E 1000). These covers incorporate MOF particles that serve as both storage reservoirs and delivery systems for the biocidal iodine. Under realistic touching conditions, the door handle covers completely inhibit the transmission of Gram-positive bacterial species (Staphylococcus aureus, and Enterococcus faecalis), Gram-negative bacterial species (Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii), and fungi (Candida albicans). The covers remain effective even after undergoing multiple contamination cycles, after being cleaned, and when tinted to improve discretion and usability. Furthermore, as the release of iodine from the door handle covers follow hindered Fickian diffusion, their antimicrobial lifetime is calculated to be as long as approximately two years. Together, these results demonstrate the potential of these antimicrobial door handle covers to prevent cross-contamination, and underline the efficacy of integrating MOFs into innovative technologies.

Intranasal Administration of Catechol-Based Pt(IV) Coordination Polymer Nanoparticles for Glioblastoma Therapy.

Cisplatin has been described as a potent anticancer agent for decades. However, in the case of glioblastomas, it is only considered a rescue treatment applied after the failure of second-line treatments. Herein, based on the versatility offered by coordination chemistry, we engineered nanoparticles by reaction of a platinum (IV) prodrug and iron metal ions showing in vitro dual pH- and redox-sensitivity, controlled release and comparable cytotoxicity to cisplatin against HeLa and GL261 cells. In vivo intranasal administration in orthotopic preclinical GL261 glioblastoma tumor-bearing mice demonstrated increased accumulation of platinum in tumors, leading in some cases to complete cure and prolonged survival of the tested cohort. This was corroborated by a magnetic resonance imaging follow-up, thus opening new opportunities for intranasal glioblastoma therapies while minimizing side effects. The findings derived from this research showed the potentiality of this approach as a novel therapy for glioblastoma treatment.