Tumor exosomes – efficient targeting vehicles for smart drug delivery and personalized therapy

As membrane‐bound extracellular vesicles, exosomes have targeting ability for specific cell types, and the cellular environment strongly impacts their content and uptake efficiency. Inspired by these natural properties, researchers from the Shanghai Jiao Tong University School of Medicine evaluated the impacts of various cellular stress conditions on the uptake efficiency of tumor iterated exosomes. They found that low‐pH treatment caused increased uptake efficiency and retained cell‐type specificity. Lipidomics analyses and molecular dynamics simulations reveal a glycerolipid self‐aggregation‐based mechanism for the enhanced homologous uptake. Furthermore, these low‐pH reprogrammed exosomes are developed into a smart drug delivery platform, which is capable of specifically targeting tumor cells and selectively releasing diverse chemodrugs in response to the exosome rupture by the near‐infrared irradiance‐triggered burst of reactive oxygen species. This platform exerts safe and enhanced antitumor effects demonstrated by multiple model mice experiments. These results open a new avenue to reprogram exosomes for smart drug delivery and potentially personalized therapy against their homologous tumor.

Culture conditions and mechanisms for enhancing exosome’s cell uptake
and its antitumor therapy applications

a) Procedure for screening cell culture conditions to obtain exosomes with high delivery efficiency, including normal condition (N), ultraviolet irradiation stress treatment (UV), low‐pH culture medium treatment (LP), high temperature treatment (HT), H₂O₂ treatment (H₂O₂), and hypoxia environment treatment (Hyp). b) Mechanism for the enhanced uptake of the lipid‐reprogrammed exosomes. c) Strategy for drug loading and synthetically anticancer therapy combining chemotherapy with photodynamic therapy.