SBA‐15 Particles As Carriers for a Series of Platinum(IV) Complexes with Oxaliplatin Scaffolds Bearing Different Anti‐Inflammatory Drugs: Promising Strategy Against Breast Cancer

Oxaliplatin is a third-generation platinum(II)-based drug mainly utilized to treat colon cancer, as part of a combinatory regime. Aiming to expand the knowledge on the effects of oxaliplatin and its derivatives on different tumor types, oxaliplatin-based platinum(IV) platforms are designed and prepared to assess their antitumor capacity against various breast cancer cell lines. In the two axial positions of the platinum(IV) system, different inflammation reducing agents, non-steroidal anti-inflammatory drugs (fenoprofen, flurbiprofen, both as racemates) and phenolic acids (acetyl-protected and unprotected ferulic acid, cinnamic acid) are incorporated as anionic ligands. The prepared platinum(IV) hybrids are loaded with great encapsulation efficiency into mesoporous SBA-15 material to serve as drug delivery vehicle, and the obtained nanostructured material can ensure very slow drug release beneficial for prolonged circulation in vivo and passive targeting. Both, free and in SBA-15 immobilized platinum(IV) complexes with oxaliplatin core, displayed potent antitumor activity in four breast cancer cell lines (MCF-7, BT-474, HCC1937 and MDA-MB-468), showing great prospect in overcoming oxaliplatin and cisplatin resistance. Mechanistic investigations in MDA-MB-468 cells of oxaliplatin and its fenoprofen derivative as the most active representative of the prepared complexes showed that the decreased cell viability resides in activation of apoptotic mechanisms.