Doxorubicin-EVs-RCT(Linyi University)

Exosomes (EVs) are promising drug carriers, with efficiency dependent on membrane proteins and drug loading capacity. Preserving EVs integrity and enabling efficient drug loading is crucial. We developed a nondestructive system using stem cell-derived EVs for tumor treatment by functionalizing the EVs surface with a cholesterol-modified T7 primer, enabling robust siRNA production via rolling circle transcription (RCT) for potent gene silencing. Results show RCT-engineered EVs with high-density siRNA enhance antitumor activity, improve serum stability, and extend tumor tissue retention. To boost efficacy, we encapsulated peptide-doxorubicin into EVs via stem cell coculture, releasing it in response to elevated matrix metalloproteinase levels. Additionally, EVs-RCT loaded with doxorubicin prolong drug blood half-life and improve chemotherapeutic outcomes. Combining intracellular drug loading via coculture with external surface engineering enhances drug payload, preserves EVs integrity, and enables more effective tumor treatment.