A versatile theranostic nanodevice based on an orthogonal bioconjugation strategy for efficient targeted treatment and monitoring of triple negative breast cancer

A novel chemical-based orthogonal bioconjugation strategy to produce tri-functionalized nanoparticles (NPs) an chemotherapy drug, doxorubicin (DOX), a near-infrared cyanine dye (Cy7) and CRGDK homing peptide, a peptide specifically binds to neuropilin-1 (Nrp-1) overexpressed on triple negative breast cancer (TNBC) cells, has been validated. These theranostic NPs have been evaluated in vitro and in vivo using an orthotopic xenotransplant mouse model using TNBC cells. In vitro assays show that theranostic NPs improve the therapeutic index in comparison with free DOX. Remarkably, in vivo studies showed preferred location of theranostic NPs in the tumor area reducing the volume at the same level than free DOX while presenting lower side effects. This multifunctionalized theranostic nanodevice based on orthogonal conjugation strategies could be a good candidate for the treatment and monitoring of Nrp-1 overexpressing tumors. Moreover, this versatile nanodevice can be easily adapted to treat and monitor different cancer types by adapting the conjugation strategy. An effective, safe and versatile nanodevice for in vivo theranostic to target tumor vasculature has been successfully developed. Herein, we reported a theranostic nanodevice based on orthogonal conjugation strategies for the multifunctionalization of polymeric NPs that contain a controlled amount of each one of the bioactive cargoes. As proof of concept, NPs carrying doxorubicin (DOX), near-infrared cyanine dye (Cy7) and a homing peptide (CRGDK), which can actively recognize a receptor overexpressed in triple negative breast cancer have been successfully validated in vitro using MDA-MB-231 tumor cell line and in vivo using an orthotopic breast cancer xenotransplant mouse model. [Display omitted]