Facilitating the Cellular Accumulation of Pt-Based Chemotherapeutic Drugs

Abstract

Cisplatin, carboplatin, and oxaliplatin are Pt-based drugs used in the chemotherapeutic eradication of cancer cells. Although most cancer patient cells initially respond well to the treatment, the clinical effectiveness declines over time as the cancer cells develop resistance to the drugs. The Pt-based drugs are accumulated via membrane-bound transporters, translocated to the nucleus, where they trigger various intracellular cell death programs through DNA interaction. Here we illustrate how resistance to Pt-based drugs, acquired through limitation in the activity/subcellular localization of canonical drug transporters, might be circumvented by the facilitated uptake of Pt-based drug complexes via nanocarriers/endocytosis or lipophilic drugs by diffusion