As a proof of concept, the surface of CriPec® nanoparticles was modified with an EGa1 nanobody targeted towards the endothelial growth factor receptor (EGFR). These CriPec ATN exhibited increased uptake in EGFR-expressing cells, as compared to unmodified CriPec nanoparticles.
14C cells incubated for 4 hours at 37 °C with (A) conjugates of EGa1-targeted CriPec nanoparticles with rhodamine and (B) plain CriPec nanoparticles with rhodamine. Rhodamine is depicted as red, Draq5 (nuclear staining) as blue.
Even more important, EGa1-targeted CriPec doxorubicin exhibited a higher efficacy in tumour mouse models as compared to conventional doxorubicin when given at their respective maximum tolerated dose (MTD). The improved survival with EGa1-targeted CriPec doxorubicin illustrates to which extent the efficacy and safety of doxorubicin are improved by using CriPec ATN.
Enhanced therapeutic efficacy of EGa1-targeted CriPec doxorubicin in a subcutaneous 14C head and neck cancer in mice. Treatment was started when tumours reached a size of 100-200 mm3. (EGa1-targeted) CriPec doxorubicin or conventional doxorubicin were administered at their respective MTD.