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Two luminescent cyclometallated IrIII complexes of the type [Ir(C^N)2(N^N)]x (X = 0 (1), and X = +1 (2)) were prepared using methyl 2-phenylquinoline-4-carboxylate as C^N ligands and either a deprotonated or protonated 3-(2-pyridyl)pyrazole as the N^N chelate. The synthesis followed a well-established and straightforward procedure. Photophysical analysis unveiled their remarkable properties, featuring phosphorescent red and orange emissions attributed to 3MLCT and 3LLCT transitions, with high emissive quantum yields in degassed DMSO solutions. Importantly, these complexes exhibited dual functionality as potent chemotherapeutic agents and photosensitisers, with their effectiveness tailored to specific cancer cell lines. Phototherapeutic treatment was particularly effective against lung cancer A549 cells, while a chemotherapeutic approach yielded superior results against breast cancer 4T1-luc2 cells. Both complexes primarily targeted lysosomes, leading to cell death through apoptotic pathways, with IC50 values in the nanomolar range. Importantly, they demonstrated no cytotoxicity against lymphocytes, mimicking the behaviour observed in healthy cells. Encouragingly, 1 and 2 exhibited minimal in vivo toxicity. The most striking finding was the exceptional chemotherapeutic efficacy of complexes 1 and 2 against 4T1-luc2 cells in BALB/c mice. These complexes surpassed the performance of the clinically employed 5-fluorouracil, especially at early tumor stages, significantly retarding 4T1-luc2 proliferation. Further investigations at vascularised and organised tumor stages revealed that complex 1 could reduce tumor size by half compared to untreated mice, which was also confirmed through tumoral weight analysis. While these findings are preliminary, the outstanding performance of these complexes at early tumor stages against breast cancer 4T1-luc2 in vivo, their selective therapeutic feasibility (chemotherapy vs. PDT) tailored to specific cancerous cell lines, and their stra

Delivering alternative strategies to deal with cancer is a huge milestone in research. Cancer cells can give a senescence response as consequence of cellular stress or external stimuli such as the use of chemotherapies, which could end up eventually in cancer relapse. Controlling cellular senescence will surely open new cancer treatment approaches. Cancer senescence induction can be used as an added timeframe to look for alternative treatments and senolytic drugs to avoid cancer relapse destroying the senescent cells (SnCs). Within cancer senescence research, metal complexes are underdeveloped in comparison with that of organic molecules or nanoparticles. Herein, we highlight the scarce investigation performed with metal complexes in the field of senescence and how a great input on them could be a huge step towards the search of alternative cancer treatments.

A new family of perylenediimide (PDI) silver and copper complexes has been successfully synthesized by reacting ortho- and bay-substituted (dipyrid-2′,2″-ylamino)perylenediimide ligands with metal phosphine fragments. The coordination of the metal center did not reveal a significant effect on the photophysical properties, which are mainly due to the PDI ligands, and in some cases quenching of the luminescence was observed. The antiproliferative effect of the free perylenediimide ligands and the metalloPDI complexes against the cervix cancer cell line HeLa was determined by MTT assay. The free perylenediimide ligands exhibited a moderate cytotoxic activity, but the coordination of silver or copper to the dypyridylamino fragment greatly enhanced the activity, suggesting a synergistic effect between the two fragments. In attempts to elucidate the cellular biodistribution of the PDIs and the complexes, a colocalization experiment using specific dyes for the lysosomes or mitochondria as internal standards revealed a major internalization inside the cell for the metal complexes, as well as a partial mitochondrial localization.

Perylenediimes (PDIs) are very interesting compounds due to their outstanding electrooptical properties, high fluorescence quantum yields, and huge versatility in their synthetic chemistry. Although PDIs are mainly used in optoelectronic applications, the number of biological studies using PDIs has been growing in the last few years. Here, we report on the synthesis and biological studies of two new families of PDIs as phototherapeutic agents. (Figure 1: a) Imidazolium-PDI, b) [AgPy2(PPh3)]-PDI). Thus, we have prepared water-soluble PDIs based on imidazolium salts as photosensitizes to generate singlet oxygen (1O2), which plays a key role in photodynamic therapy. Internalization and cytotoxicity assays were carried out in HeLa and SHSY5Y human neuroblastoma cells lines. On the other hand, taking advantage of the medicinal potential of some metals, we have synthesized new PDIs linked to silver and copper complexes to study their behavior as metallodrugs. Biological assays were also carried out in HeLa cells line.

Photodynamic therapy (PDT) is a cancer treatment still bearing enormous prospects of improvement. Within the toolbox of PDT, developing photosensitizers (PSs) that can specifically reach tumor cells and promote the generation of high concentration of reactive oxygen species (ROS) is a constant research goal. Mitochondria is known as a highly appealing target for PSs, thus being able to assess the biodistribution of the PSs prior to its light activation would be crucial for therapeutic maximization. Bifunctional Ir(III) complexes of the type [Ir(C^N)2(N^N-R)]+, where N^C is either phenylpyridine (ppy) or benzoquinoline (bzq), N^N is 2,2′-dipyridylamine (dpa) and R either anthracene (1 and 3) or acridine (2 and 4), have been developed as novel trackable PSs agents. Activation of the tracking or therapeutic function could be achieved specifically by irradiating the complex with a different light wavelength (405 nm vs. 470 nm respectively). Only complex 4 ([Ir(bzq)2(dpa-acr)]+) clearly showed dual emissive pattern, acridine based emission between 407–450 nm vs. Ir(III) based emission between 521 and 547 nm. The sensitivity of A549 lung cancer cells to 4 evidenced the importance of involving the metal center within the activation process of the PS, reaching values of photosensitivity over 110 times higher than in dark conditions. Moreover, complex 4 promoted apoptotic cell death and possibly the paraptotic pathway, as well as higher ROS generation under irradiation than in dark conditions. Complexes 2–4 accumulated in the mitochondria but species 2 and 4 also localizes in other subcellular organelles.

Heterometallic drugs are emerging as a great alternative to conventional metallodrugs. Careful selection of different metallic fragments makes possible to enhance not only the therapeutic potential by a synergistic effect, but also to incorpore key features like traceability. Drugs that integrate traceability and therapy in one system are known as theranostic agents. In cancer research, theranostic agents are becoming increasingly important. They deliver crucial information regarding their biological interplay that can ultimately be used for optimization. The well‐established therapeutic potential of PtII‐, RuII‐ and AuI‐based drugs combined with the outstanding optical properties of d6 transition metal complexes grant the delivery of traceable metallodrugs. These species can be easily fine‐tuned through modification of their respective ligands to provide a new generation of drugs.

A series of neutral and cationic heterotrimetallic complexes of the type fac-[Re(CO)3(bipy(CC)2-(AuL)2)X]n, where bipy(CC)2 is 4,4′-alkynyl-2,2′-bipyridine; L is either triphenylphosphine (PPh3), [1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene] (IPr), or tert-butyl isocyanide (CNtBu); and X is a chloride (n = 0) or acetonitrile (n = 1), were synthesized and characterized together with their Re(I) precursors, i.e., fac-[Re(CO)3(bipy(CC)2)X]n. X-ray diffraction of complexes 1, 3, and 6 corroborated the expected octahedral and linear distribution of the ligands along the Re(I) and Au(I) centers, respectively. Luminescent studies showed that all the complexes displayed a broad emission band centered between 565 and 680 nm, corresponding to a 3MLCT from the Re(I) to the diimine derivative. The presence of the gold fragment coordinated to the diimine ligand shifted in all cases the emission maxima toward higher energies. Such an emission difference could be potentially used for assessing the precise moment of interaction of the probe with the biological target if the gold fragment is implicated. Antiproliferative studies in cancer cells, A549 (lung cancer) and HeLa (cervix cancer), showed a generalized selectivity toward HeLa cells for those heterotrimetallic species incubated at longer times (72 vs 24 h). ICP-MS spectrometry revealed the greater cell internalization of cationic vs neutral species. Preliminary fluorescence microscopy experiments showed a different behavior of the complexes in HeLa and A549 cell lines. Whereas the complexes in A549 were randomly distributed in the outside of the cell, those incubated with HeLa cells were located close to the cellular membrane, suggesting some type of interaction, and possibly explaining their cellular selectivity when it comes to the antiproliferative activity displayed in the different cell lines.

La química bioinorgánica ofrece nuevas oportunidades en el ámbito del diseño de agentes terapéuticos con excelentes propiedades biológicas. Dentro de este contexto, existe un creciente interés centrado en el desarrollo de complejos heterometálicos como potenciales agentes de visualización celular y terapia contra el cáncer. Es factible pensar que se produzca un efecto sinérgico cuando se combina un fragmento metálico bioactivo y otro con propiedades luminiscentes, y por lo tanto, permitiría la creación de fármacos rastreables. Este trabajo describe el desarrollo de una nueva variedad de complejos heterometálicos luminiscentes mediante la utilización de un ligando politrópico L, 4, 4’-dietinil-2, 2’- bipiridina. En primer lugar se obtienen los complejos alquinilo con fragmentos AuPR3+, donde PR3 puede ser trifenilfosfina, (2-bifenil)di-terc-butilfosfina (JohnPhos) o 4- sulfofenil-difenilfosfina. Posteriormente se produce la coordinación de compuestos de Cu(I), Ag(I) o Re(I) a la unidad bipiridina del ligando, los cuales resultan adecuados para imagen celular y cuyas propiedades fotofísicas modificadas se espera que superen algunos de los problemas asociados con los medicamentos tradicionales rastreables. Por lo tanto, se realizaron estudios fotofísicos para las especies citadas mediante espectroscopía UV-visible y de fluorescencia para evaluar su idoneidad para ser usados como agentes de imágen y su actividad citotóxica en células de cáncer de pulmón humano; células A549, las cuales también se analizaron para revelar su potencial como una nueva generación de agentes de contraste y terapia.

We present a very simple spray-coating method for depositing cobalt catalyst over quartz substrates that can be efficiently utilized in the production of carbon nanotubes (CNTs) by thermal chemical vapor deposition (CVD). Very uniform multi-walled carbon nanotubes (MWNTs) have been grown from cobalt catalyst over large surfaces by thermal CVD using mixtures of acetylene and ammonia. The effect of catalyst pretreatments and CNT growth temperature on the CNT diameter has been studied and discussed.

A very simple spray-coating method is presented here for depositing iron salt and iron sol-gel solutions on quartz and alumina substrates that can be efficiently used to produce carbon nanotubes (CNTs) by thermal chemical vapor deposition (CVD). Aligned and curly and randomly oriented multi-walled carbon nanotubes (MWNTs) have been efficiently grown from iron catalyst over large surfaces using mixtures of acetylene and ammonia under different experimental conditions. The effect of substrate, catalyst precursor, thermal and reductive catalyst pretreatment, and CNT growth temperature on the CNT diameter and morphology have been here studied and discussed.