Background: Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response.
Results: Here we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV365nm irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells.
Conclusions: This work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer.
Dr. Rafael Vazquez‑Duhalt is full professor at the Center for Nanosciences and Nanotechnology of the National University of Mexico and Head of the Department of Bionanotechnology. He is Industrial Chemical Engineer from the National Polytechnic Institute in Mexico City. Dr. Vazquez-Duhalt completed postgraduate studies in Analytical Chemistry of the Environment at the University of Geneva, Switzerland, and in Human Ecology in a program sponsored by seven European Universities. He earned the PhD degree in Biological Sciences from the University of Geneva, Switzerland. In addition, Dr. Vazquez-Duhalt carried out a three-years Postdoctoral work in the University of Alberta, Canada, and he has been visiting Professor at the University of Maryland and at the University of California, San Diego.
Among others, Dr. Rafael Vazquez-Duhalt has earned the following prizes: The Scopus Prize from Elsevier Publisher to Mexican researcher with higher H factor Biotechnology and Agronomy fields in 2011. The “Thomson-Reuters” Prize to the most cited Mexican research article in Microbiology in the decade 1999-2009 in 2009. Dr. Vazquez-Duhalt is author of four patents, and he has published 2 books and more than 160 scientific articles with more than 4500 cites and an H of 39 (Scopus). Prof. Vazquez-Duhalt is Editor-in-chief of the journal “Biocatalysis” (de Gruyter, Germany) and member of the editorial boards of 5 scientific journals. Dr. Vazquez-Duhalt is Associate Director of the CaliBaja Center for Resilient Materials and Systems at the Jacobs School of Engineering, University of California at San Diego, USA.