"The aim of the proposed research is to develop a new (Au-NP) gold nanoparticle-based drug delivery systems. For this new synthetic approach, three different components are designed; namely, new tailored gold nanoparticle, cleavable linkers, and new platinum-based drugs.The first component is a new tailored Au-NP, which will be synthesized using a multidentate thioether “coating ligand”. Unlike the gold nanoparticle-based nanocarriers used till date, this novel nanomaterial enables accurate functionalization of the particle surface using a multidentate ligand, allowing also controlled particle size and shape. Moreover, tuning of the gold-surface properties is easily performed by functionalization of the coating ligand, leading to a well defined drug load per particle. The functionalization also enables the attachment of linkers (second component of the system) of a programmable variety on the outer-shell of the Au-NP, which will serve as bridges between the nanocarrier and the drug.The proposed approach is the use of cleavable linkers to reach a new level of drug-controlled release. Inspired by cancer biology, peptide linkers will be attached to the coating ligand of the gold nanoparticle. These peptides will be cleaved by overexpressed proteases in cancer tissue, achieving tumor-specific drug (endogenous) release. In addition, exogenous activation of drug release using photolabile linkers will be explored, leading to new class of external controlled platinum drug release.To test this approach, platinum-based drugs (third component), which display high cure rates against several cancers (ovarian, head neck, testicular and lung cancer), will be attached to the nanocarriers using different cleavable linkers. In addition to the synthesis and characterization of these systems, in vitro studies in cancer cells will be performed to investigate their cellular processing, and establish their mechanisms of action."