Superficial Modification of Exosomes for Cancer Cell Targeting

Cancer is a global health concern with growing prevalence, incidence and mortality rates, especially in developing countries. Main reasons for failure of current therapeutic modalities include metastasis of cancer cells and their innate/acquired resistance to chemoradiotherapy. To introduce novel strategies against metastatic and resistant cancer cells, recent attempts have focused on engineering of biogenic exosomes. These natural vehicles could be used to directly transfer drugs, therapeutic microRNAs and proteins to cancer cells. To enhance efficacy of exosome-mediated delivery, the superficial structures of exosomes could be modified to facilitate targeted uptake only by cancer cells. In this regard, engineered exosomes that express GE11 peptide, which binds to epidermal growth factor receptor on tumor cells with epithelial origin, effectively deliver their drug cargo to tumor cells. Likewise, expression of exosomal membrane protein Lamp2B fused to Interleukin 3 receptor, which is overexpressed on leukemia cells, enhanced exosome specificity in vivo. Besides modifying exosomes by a ligand on their surface to target cancer cells, they could also be engineered to induce cell death, as reported for TRAIL+ exosomes that express tumour necrosis factor-related apoptosis-inducing ligand. Although various approaches were used to modify structure and function of exosomes, a thorough understanding of their biology is still necessary before translating this exciting approach to clinical studies.

کلیدواژه ها:

Exosome ، Surface Modification ، Cancer Therapy