Lipoplatin

Lipoplatin (Liposomal cisplatin) is a nanoparticle of 110 nm average diameter composed of lipids and cisplatin. This new drug has successfully finished Phase I, Phase II and Phase III human clinical trials. It has shown superiority to cisplatin in combination with paclitaxel as a chemotherapy regimen in non-small cell lung cancer (NSCLC) adenocarcinomas.

Lipoplatin evades immune surveillance thus escaping clearance from macrophages, circulates for long periods in body fluids after intravenous administration with a half-life of ~120 h, and extravasates through the compromised endothelium of the vasculature in tumors created during the process of neoangiogenesis Extravasation Figure. Thus, Lipoplatin nanoparticles are concentrated to the primary tumor and metastases. Human studies have shown 40- to 200-fold higher platinum concentration compared to the adjacent normal tissue in specimens from human biopsies 20h post-infusion of the drug. Lipoplatin nanoparticles once inside the tumor cell mass can fuse with the cell membrane because of the presence of the fusogenic lipid DPPG in their lipid bilayer; an alternative mechanism proposed is that Lipoplatin is taken by endocytosis by tumor cells as shown from Lipoplatin containing fluorescent lipids and imaging of the tumor cells in culture thus treated with fluorescent microscopy. These processes occurring at the cell membrane level are promoted by the lipid shell of the nanoparticles (disguised as nutrients). The technology allows Lipoplatin to empty its toxic payload (cisplatin) inside the cytoplasm to kill the tumor cell. The cell membrane is considered a significant barrier to transportation of the toxic molecules of cisplatin across and inside the tumor cell.

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