Orthotopic Breast Cancer Model to Investigate the Therapeutic Efficacy of Nanobody-Targeted Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is characterized by the local application of laser light, which activates a photosensitizer to lead to the formation of singlet oxygen and other toxic reactive oxygen species, to finally kill cells. Recently, photosensitizers have been conjugated to nanobodies to render PDT more selective to cancer cells. Nanobodies are the smallest naturally derived antibody fragments from heavy-chain antibodies that exist in animals of the Camelidae family. Indeed, we have shown that nanobody-targeted PDT can lead to extensive and selective tumor damage, and thus the subsequent step is to assess whether this damage can delay or even inhibit tumor growth in vivo. To evaluate the therapeutic efficacy of PDT, mouse models are mostly employed in which human tumors are grown subcutaneously in the flank of the animals. Although very useful, it has been suggested that these tumors are further away from their natural environment and that tumors developed in the organ or tissue of origin would be closer to the natural situation. Thus, this chapter describes the development of an orthotopic model of breast cancer and the application of nanobody-targeted PDT, for the assessment of the therapeutic efficacy.