Combretastatin A‑4 Analogue: A Dual-Targeting and Tubulin Inhibitor Containing Antitumor Pt(IV) Moiety with a Unique Mode of Action

Three new Pt­(IV) complexes comprising a combretastatin A-4 analogue were designed and synthesized. The resulting antitumor Pt­(IV) complexes could significantly improve the antiproliferative activity and overcome the drug resistance of cisplatin in vitro. Interestingly, these novel compounds not only can carry the DNA binding Pt­(II) warhead into the cancer cells but also have a small molecule fragment that can inhibit tubulin polymerization. Among them, complex <b>13</b>, which was attached to an inhibitor of tubulin at one axial position of Pt­(IV) octahedral coordination sphere, could effectively enter cancer cells, arrest the cell cycle in HepG-2 cancer cells at G2/M phases, and induce activation of caspases triggering apoptotic signaling via the mitochondrial-dependent apoptosis pathways. Moreover, complex <b>13</b> has the ability to effectively inhibit the tumor growth in the HepG-2 xenograft model without causing significant loss of animal body weight in comparison with cisplatin

A Unique Chemo-photodynamic Antitumor Approach to Suppress Hypoxia via Ultrathin Graphitic Carbon Nitride Nanosheets Supported a Platinum(IV) Prodrug

Tumor hypoxia severely restrains the efficiency of irreversible O2-consumption photodynamic therapy. The deep hypoxia induced by photodynamic therapy can promote the level of hypoxia inducible factor 1α that participates in many tumor processes and eventually lead to poor therapeutic outcomes. Herein, a chemo-photodynamic antitumor strategy based on ultrathin graphitic carbon nitride nanosheets loaded with a hypoxia-targeting platinum(IV) prodrug is reported. Under low-intensity visible light irradiation, such integrated nanosheets effectively generate reactive oxygen species together with DNA binding platinum species to achieve enhanced antiproliferation efficacy by downregulating HIF-1α under hypoxic conditions