About this Research Topic
The coordination compound cis-diamminedichloridoplatinum(II), also known as cisplatin, received FDA approval in 1978 for the treatment of testicular cancer, spawning a massive clinical interest in metallodrugs and representing the birth of the modern Medicinal Inorganic Chemistry. Since then, a plethora of metallo-drugs have been investigated for their use in the treatment of cancer, diseases incited by microbes and viruses, and for many other biological applications. Cisplatin has been so successful as an anticancer drug that very few other analogues (e.g., carboplatin, oxaliplatin, nedaplatin, lobaplatin, and heptaplatin) have received approval for use in the clinic. Unfortunately, many side effects and the development of chemoresistance partially limit the efficacy of platinum-based anticancer drugs. Consequently, platinum(IV) prodrugs were designed to obtain a concrete improvement to traditional platinum(II) therapy. In fact, the Pt(IV) metal center is more inert towards substitution reactions than Pt(II), limiting off-target reactions and side effects. Octahedral Pt(IV) complexes, under the hypoxic conditions of tumor tissue/cells, may be selectively reduced with consequent release of the two axial ligands and generation of the corresponding Pt(II) antitumor species, increasing the selectivity.
Desirable properties of a Pt-prodrug may be obtained by rational design of the axial ligands that represent a powerful tool to impart optimal hydro-/lipo-philicity, red-ox stability, specific targeting and delivery, improved cellular uptake, and drug accumulation. Consequently, some Pt(IV) prodrugs have entered clinical trials without results evidencing advantages over their corresponding Pt(II) counterparts. With this Research Topic we want to foster and promote the design and development of platinum-based prodrugs with i) a wider spectrum of activity and less side effects, and ii) ligands specifically targeted towards tumors or endowed with pharmacological activity. In addition, preclinical investigations are strongly encouraged, as well as investigations on the effects of the equatorial ligands. Finally, since Pt(IV) complexes are well-known for their stability, including low-pH stability, we want to boost the development of low-pH stable, and hence orally administrable Pt(IV) prodrugs, with the final aim of improving oncologic patients’ compliance.
We are interested in Original Research papers as well as Review Articles on the topics listed below.
• Design and synthesis of Pt-prodrugs for targeted delivery.
• New Pt(IV) prodrugs with multiple action due to rational design of axial bio-active ligands.
• New Pt(IV) prodrugs photoactivable for PACT (photoactivated chemotherapy) or PDT (photodynamic therapy).
• New bio/chemically triggered (e.g. pH sensitive, redox responsive, enzyme activatable) Pt prodrugs.
• New supramolecular Pt(IV) prodrugs.
• Development of novel Pt(IV) prodrugs for oral administration.
Preclinical investigation, and studies focusing on the pharmacology and/or biological mode of action of novel prodrugs should be submitted via Frontiers in Pharmacology.
Prof. Nicola Margiotta is the inventor of patent US9220705B2, the other Topic Editors declare no conflicting interests.
Keywords: cisplatin; oxaliplatin; anticancer drugs; platinum prodrugs; platinum(IV), drug targeting and delivery, nanodrugs, chemoresistance
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.