Postdoctorate, Centro de Nanosciencias y Nanotecnologia, Universidad Nacional Autónoma de México (UNAM)
Development of biocatalytic virus-like-nanoparticles as nanoplatforms for multimodal cancer therapy
Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, tumors have low CYP concentration, and thus, maximum prodrug transformation occurs at liver causing severe systemic toxicity. Combination therapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response. Here we show the modular design of P22 bacteriophage virus-like particles (VLP) for nanoscale integration of virus-driven enzyme prodrug therapy (EPT) and photodynamic therapy (PDT). These virus capsids carrying CYP activity at the core are decorated with photosensitizer (PS) and targeting moiety at the surface for effective combinatory treatment. The final biocatalytic nanoparticle, P22CYP-PpIX-PEG(EST) is recognized by 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 synergy between the two modalities drastically enhanced the tamoxifen sensitivity leading to a strong inhibition of tumor cells. Thus, the targeted combination of EPT and PDT using multivalent biomimetic VLPs represent a promising approach for effective therapy of ER+ breast cancers.