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Abstract A series of 4-ethynylaniline gold(I) complexes containing monophosphane (1,3,5-triaza-7-phosphaadamantane (pta; 2), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (3), and PR3, with R=naphthyl (4), phenyl (5), and ethyl (6)) and diphosphane (bis(diphenylphosphino)acetylene (dppa; 7), trans-1,2-bis(diphenylphosphino)ethene (dppet; 8), 1,2-bis(diphenylphosphino)ethane (dppe; 9), and 1,3-bis(diphenylphosphino)propane (dppp; 10)) ligands have been synthesized and their efficiency against tumor cells evaluated. The cytotoxicity of complexes 2–10 was evaluated in human colorectal (HCT116) and ovarian (A2780) carcinoma as well as in normal human fibroblasts. All the complexes showed a higher antiproliferative effect in A2780 cells, with the cytotoxicity decreasing in the following order 5>6=9=10>8>2>4>7>3. Complex 4 stands out for its very high selectivity towards ovarian carcinoma cells (IC50=2.3 μm) compared with colorectal carcinoma and normal human fibroblasts (IC50>100 μm), which makes this complex very attractive for ovarian cancer therapy. Its cytotoxicity in these cells correlates with the induction of the apoptotic process and an increase of intracellular reactive oxygen species (ROS). The effects of the nuclearity, rigidity, and solubility of these complexes on their biological activity were also analyzed. X-ray crystal structure determination allowed the identification of short N−H⋅⋅⋅π contacts as the main driving forces for the three-dimensional packing in these molecules.

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Nanoparticles possess unique optical and physic-chemical properties that may potentiate applications in biomedicine, in particular in diagnostics, therapy and imaging. Advances on biomolecular diagnostics strategies have greatly focused on single molecule detection and characterization of DNA, RNA or proteins through improved nanoparticle-based platforms. Nanoparticles improve analytical capability when compared to traditional techniques with high resolution and medium-high throughput. Also, particular interest has been directed at SNP detection, gene expression profiles and biomarker characterization through colorimetric, spectrometric or electrochemical strategies.
Molecular imaging has also benefited from the introduction of nanoparticles in standard techniques towards non-invasive imaging procedures that can be used to highlight regions of interest, allowing the characterization of biological processes at the cellular and/or molecular level. Several imaging modalities are associated with low sensitivity, an issue that can be tackled by the use of probes, e.g. contrast agents for X-ray and magnetic resonance imaging, radiolabelled molecules for nuclear medicine. Furthermore, nanoparticles can be used as vehicles that deliver specifically these contrast agents, leading to overcome the limitations of conventional modalities.
This chapter will discuss the use of nanoparticles in biomolecular recognition and imaging applications, focusing those already being translated into clinical settings. Current knowledge will be addressed as well as its evolution towards the future of nanoparticle-based biomedical applications.

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Cancer is considered the most aggressive malignancy to humans, and definitely the major cause of death worldwide. Despite the different and heterogenous presentation of the disease, there are pivotal cell elements involved in proliferation, differentiation, and immortalization, and ultimately the capability to evade treatment strategies. This is of utmost relevance when we are just beginning to grasp the complexity of the tumor environment and the molecular “evolution” within. The tumor micro-environment (TME) is thought to provide for differentiation niches for clonal development that results in tremendous cancer heterogeneity. To date, conventional cancer therapeutic strategies against cancer are failing to tackle the intricate interplay of actors within the TME. Nanomedicine has been proposing innovative strategies to tackle this TME and the cancer cells that simultaneously provide for biodistribution and/or assessment of action. These nanotheranostics systems are usually multi-functional nanosystems capable to carry and deliver active cargo to the site of interest and provide diagnostics capability, enabling early detection, and destruction of cancer cells in a more selective way. Some of the most promising multifunctional nanosystems are based on gold nanoparticles, whose physic-chemical properties have prompt for the development of multifunctional, responsive nanomedicines suitable for combinatory therapy and theranostics. Herein, we shall focus on the recent developments relying on the properties of gold nanoparticles as the basis for nanotheranostics systems against the heterogeneity within the TME.

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Over the past few years, modern medicinal chemistry has evolved towards providing us new and alternative chemotherapeutic compounds with high cytotoxicity towards tumor cells, alongside with reduced side effects in cancer patients. Organometallic compounds and their unique physic-chemical properties typically used in homogenous catalysis are now being translated as potential candidates for medical purposes. Their structural diversity, ligand exchange, redox and catalytic properties make them promising drug candidates for cancer therapy. Over the last decade this area has witnessed a steady growth and a few organometallic compounds have in fact already entered clinical trials, emphasizing its increasing importance and clinical relevance. Here we intend to stress out the different applications of organometallic compounds in medicine with emphasis on cancer therapy, as well as address setbacks regarding formulation issues, systemic toxicity and off-target effects. Advantages over classical coordination metal complexes, their nanovectorisation and specific molecular targets are also discussed.

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