Tailored Beta-Lapachone Nanomedicines for Cancer-Specific Therapy.

Nanotechnology shows the power to improve efficacy and reduce the adverse effects of anticancer agents. As a quinone-containing compound, beta-lapachone (LAP) has been widely employed for targeted anti-cancer therapy under hypoxia. The principal mechanism of LAP-mediated cytotoxicity is believed due to the continuous generation of reactive oxygen species (ROS) with the aid of NAD(P)H: quinone oxidoreductase (NQO1). The cancer selectivity of LAP relies on the difference between NQO1 expression in tumors and that in healthy organs. Despite this, the clinical translation of LAP faces the problem of narrow therapeutic window that is challenging for dose regimen design. Herein, we briefly introduce the multifaceted anti-cancer mechanism of LAP, review the advance of nanocarriers for LAP delivery, and summarize the combinational delivery approaches to enhance LAP potency in recent years. We also present the mechanisms by which nanosystems boost LAP efficacy, including tumor targeting, cellular uptake enhancement, controlled cargo release, enhanced Fenton or Fenton-like reaction, and multidrug synergism. The problems of LAP anti-cancer nanomedicines and the prospective solutions have been discussed. The current review may help to unlock the potential of cancer-specific LAP therapy and speed up its clinical translation. This article is protected by copyright. All rights reserved.