Severe side effects of
chemotherapy agents on vital organs are the major causes of
cancer-related mortality, not merely
cancer disease. Encapsulating chemotherapeutic molecules in nanocarriers is a justifiable
solution in decreasing the risk of their side effects and boosting the efficiency of treatment. The present study has developed the
doxorubicin (DOX)-loaded
AS1411 (anti-
nucleolin) aptamer surface-functionalized exosome (DOX-
Apt-Exo) to treat
colorectal cancer in both in-vitro and in-vivo experimental models. HEK293-derived exosomes were loaded with DOX through the incubation method with a nearly 13% encapsulation efficiency. Afterwards, the 5-terminal carboxyl group of AS1411-aptamer was converted into
amine-reactive NHS
esters with
EDC/NHS amide coupling chemistry before being conjugated to the
amine groups on the exosome surface. DLS and TEM estimated the designed formulation (DOX-
Apt-Exo) size of about 200 nm. Aptamer-binding affinity and cellular uptake of DOX-
Apt-Exo by
nucleolin-overexpressing
cancer cells were depicted through fluorescence microscopy. Comparing the in-vitro cytotoxicity impact of DOX-loaded exosomes, either targeted or non-targeted by MTT assay, clearly verified a high effectiveness of
ligand-receptor mediated target
therapy. Subsequently, in-vivo experiments which were conducted on four groups of ectopic mouse models of
colon cancer (5 in each group) demonstrated the
tumor growth suppression through professional long-term accumulation and retention of DOX-
Apt-Exo at the
tumor site by
ligand-receptor interaction. The results suggested that
AS1411 aptamer-functionalized exosomes can be recommended as a safe and effective system to site-specific drug delivery in possible clinical applications of
colon cancer.