Dual-targeted Delivery of Doxorubicin by Mesoporous Silica Nanoparticle Coated with AS1411 Aptamer and RGDK-R Peptide to Breast Cancer in Vitro and in Vivo

Statistics show that breast cancer is the first cause of cancer-related deaths in women worldwide. Doxorubicin (DOX) is one of the chemotherapeutics with high efficacy in breast cancer. Nevertheless, due to its lack of specificity, it causes severe adverse effects and that is how the targeting delivery to cancer cells with high precision and efficiency becomes crucial. Combining nanoparticles and active targeting agents in forming a drug delivery system (DDS) for cytotoxic drugs is a promising strategy to circumvent the drawbacks of chemotherapy. Herein, a new dual-targeting delivery system for DOX was fabricated by loading DOX into mesoporous silica nanoparticles (MSN) which were then covalently attached to AS1411 aptamer and electrostatically conjugated to RGDK-octa-arginine peptide sequence (RGDK-R). The in vitro data elucidated a significant safety effect of the encapsulated DOX in MSN.COOH decorated with AS1411 and RGDK-R for non-cancerous cells, while the same toxicity as DOX towards breast cancer cells. In vivo results indicated that the designed system could effectively improve the inhibitory effect of DOX on tumor growth with single-dose administration.