Targetable Clinical Nanoparticles for Precision Cancer Therapy Based on Disease-Specific Molecular Inflection Points.

Abstract

Novel translational approaches based on clinical modular nanoplatforms are needed in order to treat solid cancers according to their discrete molecular features. In the present study, we show that the clinical nanopharmaceutical Ferumoxytol, which consists of a glucose-based coat surrounding an iron oxide core, could identify molecular characteristics of prostate cancer, corresponding to unique phases of the disease continuum. By affixing a targeting probe for the prostate-specific membrane antigen on its surface, the nanopharmaceutical was able to assess the functional state of the androgen receptor pathway via MRI, guiding therapy and delivering it with the same clinical nanoparticle. In order to simultaneously inhibit signaling from key oncogenic pathways of more advanced forms of prostate cancer, a single-agent therapy for early stage disease to inhibit DNA replication, as well as combination therapy with two drugs co-retained within the nanopharmaceutical's polymeric coating, were tested and resulted in complete tumor ablation. Recalcitrant and terminal forms of the disease were effectively treated with a nanopharmaceutical delivering a combination that upregulates endoplasmic reticulum stress and inhibits metastasis, thereby showing that this multifunctional nanoplatform can be used in the clinic for patient stratification, as well as precision treatment based on the individual's unique disease features.