## 2 Drug Delivery Systems  
Conventional cancer treatments, such as chemotherapy and radiotherapy, act in biological systems in a non-specific way, affecting both malignant and healthy cells. This affects the optimal therapeutic and implementation of gold derivatives.  
Targeted delivery through gold derivatives can take place through two types: passive and active effect, reducing unwanted effects and the development of drug resistance [25]. Passive targeting allows the accumulation of a drug or drug transport system within a specific site due to the variation of physicochemical or pharmacological factors. This type of method exploits the size of the nanoparticles and the properties of the tumor vascular system, effectively improving the bioavailability and efficacy of the drug. The vascularity of the tumor is very different from normal tissue, in fact the blood vessels of the tumor tissues, unlike those in normal tissues, have spaces between the adjacent endothelial cells up to 600-800 nm. These pathophysiological features of tumor vessels induce the Enhanced permeability and retention EPR (Enhanced Permeability and Retention) effect, which allows macromolecules, including nanoparticles, to extravasate through these extravascular spaces and accumulate within tumor tissues [26]. The accumulation of tumor drugs is ten times greater when the drug is administered from a nanoparticle rather than as a free drug. Another contributor to passive targeting is the unique microenvironment that surrounds cancer cells, which is different from that of normal cells. Fast-growing hyperproliferative cancer cells use glycolysis for extra energy, resulting in an acidic environment. The pH-sensitive liposomes are designed to be stable at a physiological pH but degraded to release the active drug into target tissues where the pH is lower, such as in the acidic environment of cancer cells [27]. Active targeting involves the attachment of a fraction, such as a monoclonal antibody or a ligand, to deliver a drug to pathological sites or to cross biological barriers based on molecular recognition processes [28; 29; 30]. When designing the synthesis of nanoparticles, it is necessary to consider some factors: for example, the antigen or receptor should be expressed exclusively and homogeneously on tumor cells and not expressed on healthy ones. The internalization of conjugates occurs through receptor-mediated endocytosis. Indeed, when a conjugate binds to its receptor on the cell surface, the plasma membrane envelops the receptor and ligand complex to form an endosome, this is transferred to target organelles.  
When the pH value inside the endosome becomes acidic and lysozymes are activated, the drug is released from the conjugate and enters the cytoplasm. The receptor released by the conjugate returns to the cell membrane to begin a second transport cycle by binding with new conjugates. Ligands targeting cell surface receptors can be natural substances that have the advantages of a molar mass and lower immunogenicity than antibodies. Molecular targeted therapy is a potential solution to overcome these challenges, it can be achieved through smart design (Figure 1). Both methods allow increasing the concentration of the anticancer drug directly inside the tumor cell, causing the decrease of toxicity for healthy cells [30]. Gold derivatives (gold compounds, complexes and nanoparticles) can be conjugated to a wide range of biologically active organic molecules, designed to cross the blood-brain barrier, interact with specific receptors entering the cell through an alternative path. In particular, passive targeting of gold nanoparticles is based on the effect of enhanced permeability and retention (EPR) and tumor angiogenesis, while active targeting is based on direct binding from the ligand to receptors expressed by tumor cells [26]. Antitumor agents can be released as a function of pH or temperature [31; 32].