###### Abstract  
The introduction of biologically relevant organic moieties in the coordination sphere of transition metal complexes has recently become a well-established strategy to increase the selectivity and biocompatibility of metallodrugs. In this review, the major advances achieved in this area of research in the last three years are described in detail. Particular attention is given to the metal complexes bearing the main biomolecules of life: carbohydrates, lipids, nucleotides, proteins and vitamins. Each paragraph summarizes the synthetic strategy employed to obtain the complexes of interest as well as the most interesting biological results obtained with these potential metallodrugs. Moreover, the structure-activity relationships observed by the different research groups are described and discussed, with the goal of suggesting to the reader the ligand/metal centre combinations that provide the most promising results in the fight against cancer. Some of the compounds examined in this review as well as other bioconjugated metal complexes published in recent decades exhibit interesting selectivity towards cancer cells over normal ones and a specific mode of action. These latter aspects are the basis of what is commonly known as _anticancer target therapy_. bioconjugation; carbohydrates; amino acids and proteins; lipids and steroids; nucleic acids; vitamins; metallodrugs +
Footnote †: journal: Medical  
approval of this compound for clinical use in 1978 paved the way for the use of metal-based compounds for cancer therapy [5; 6]. The high reactivity of metal complexes in the biological environment has made it difficult to predict their toxicity and therapeutic properties by computational methods (e.g., molecular docking), making the in vitro and in vivo screening steps indispensable [1; 4; 7; 8]. Despite the huge number of metal-based compounds with interesting in vitro and in vivo anticancer properties, cisplatin and its second- and third-generation derivatives (e.g., carboplatin and oxaliplatin) remain the gold standards for the treatment of 50-70% of solid tumours. However, the non-negligible side-effects of platinated anti-neoplastic agents (e.g., nephrotoxicity, hepatotoxicity, neuro- and ototoxicity, cardiotoxicity, haematological and gastrointestinal toxicity) and their ineffectiveness towards some types of aggressive tumours (e.g., high-grade serous ovarian cancer, HGSOC) are the main limitations of this category of metallodrugs. All these issues as well as some suggestions for the design of new generations of metal-based anticancer agents are well described in recent reviews on this topic [6; 9; 10; 11]. In particular, the investigation of complexes containing metals other than platinum and/or the development of efficient drug delivery systems (e.g., lipophilic) are the two most prominent solutions proposed in these contributions [12]. The complexity of this area of research since the discovery of cisplatin has been well described in recent reviews from the [PERSON] [13] and [PERSON] groups [14]. More specifically, they defined metallodrugs as unique metal-ligands combinations which, due to the wide range of processes that they can promote in the biological environment, can be considered challenging but extremely versatile and multitarget compounds. Their main mode of action depends on the activation mechanism, which is intimately related to the nature of metal centre and coordinated ligands, as well as the geometry and the overall stability of the complex in biological media. For this reason, the choice of biological assays and analytical techniques in the study of the mechanism of action of new metal-based drug candidates is extremely important to avoid false-positive or false-negative results [14]. The numerous studies conducted in the last 50 years on the activation mechanisms of metallodrugs in the biological environment have allowed researchers to classify metal complexes according to various criteria. A first subdivision is that between _functional_ and _structural_ compounds.