Novel metal-based anticancer drugs: a new challenge in drug delivery

Since the serependitous discovery of the cisplatin antiproliferative activity, many efforts have focused on the design of potent metal-based drugs for oncology therapies. A large number of these complexes have been evaluated in vitro and in vivo and some have reached clinical trials. However, while metallodrug chemistry has developed to an advanced level, these emerging therapeutics have encountered new hurdles including poor water solubility and pharmacological deficiencies. Today, solutions to overcome these issues do not lie in synthesizing new anticancer drugs but in finding suitable drug delivery strategies. Over the past decades, various delivery systems have been developed including prodrug, ligand design and nanocarriers aimed at enhancing the performance profile of these novel metallodrugs

Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules

Recently developed drug delivery nanosystems, such as lipid nanocapsules (LNCs), hold great promise for the treatment of glioblastomas (GBs). In this study, we used a subpopulation of human mesenchymal stem cells, "marrow-isolated adult multilineage inducible" (MIAMI) cells, which have endogenous tumor-homing activity, to deliver LNCs containing an organometallic complex (ferrociphenol or Fc-diOH), in the orthotopic U87MG GB model. We determined the optimal dose of Fc-diOH-LNCs that can be carried by MIAMI cells and compared the efficacy of Fc-diOH-LNC-loaded MIAMI cells with that of the free-standing Fc-diOH-LNC system. We showed that MIAMI cells entrapped an optimal dose of about 20 pg Fc-diOH per cell, with no effect on cell viability or migration capacity. The survival of U87MG-bearing mice was longer after the intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells than after the injection of Fc-diOH-LNCs alone. The greater effect of the Fc-diOH-LNC-loaded MIAMI cells may be accounted for by their peritumoral distribution and a longer residence time of the drug within the tumor. These results confirm the potential of combinations of stem cell therapy and nanotechnology to improve the local tissue distribution of anticancer drugs in GB