Co-delivery of doxorubicin and α-PCNA aptamer using AS1411-modified pH-responsive nanoparticles for cancer synergistic therapy

Abstract

Herein, a novel nanotherapeutic delivery platform was designed for subcellular co-delivery of α-PCNA aptamer as therapeutic aptamer and doxorubicin (Dox) as chemotherapy drug to tumor cells. Firstly, Dox was loaded onto the α-PCNA aptamer. Then, Dox-loaded α-PCNA was condensed by LAH4-L1 as a short cationic amphipathic peptide (LDPNs). Subsequently, the LDPNs was coated with AS1411 aptamer as targeting agent to obtain a therapeutic delivery system for tumor synergistic therapy. The results showed that the AS1411-modified LDPNs was stable in serum and could effectively accumulate at tumor site and be internalized into MCF-7 and 4T1 cells (target cells) through AS1411 and LAH4-L1. Also, the AS1411-modified LDPNs released its therapeutic agents in response to acidic conditions inside the cells. The superior anticancer activity of the AS1411-modified LDPNs compared to free Dox and other formulations was proved in 4T1 mouse breast cancer model. Overall, the results indicated that co-delivery of Dox and α-PCNA using AS1411 and LAH4-L1 can be used as a new approach to improve chemotherapy of breast cancer with less adverse effects and has great capacity for the clinical translation.