Engineering of combination drug delivery of pH/reduction response potential nanocarrier for the treatment of liver cancer

Combination cancer therapy may be facilitated using a nanoparticle-based drug delivery system. However, the therapeutic efficiency of cancer nanomedicines is reduced due to poor drug release into the cancer cells. To the treatment of liver malignancy, a PEGylated poly(α-lipoic acid) copolymer with mPEG-αPLA was constructed and exploited as a dual reduction/pH response nanocarrier to delivery of capsaicin (CAP) and doxorubicin (DOX). Due to their self-assembly in an aqueous solution, the mPEG-αPLA amphiphilic polymers could be effectively encapsulated on CAP and DOX to synthesize CAP and DOX co-loaded nanomaterials (CAP/DOX@NPs). After being prepared, the CAP/DOX@NPs released more CAP and DOX in response to reduction and acid stimuli than those left undamaged. According to the results of flow cytometry and confocal laser scanning microscopy, the HepG2 liver cancer cells rapidly absorbed the dual-drug-loaded nanoparticles and released drugs intracellularly. As a result, in HepG2 cells, CAP/DOX@NPs promoted increased cell death and had synergistic therapeutic effects. In biochemical models such as acridine orange and ethidium bromide (AO/EB and nuclear DAPI staining), results were demonstrating the nanoparticles effectively induce apoptosis in HepG2 liver cancer cells. Moreover, in vivo systemic toxicity outcomes shown that the CAP/DOX@NPs could be quickly excreted from the body with no apparent toxicity signs. Overall, these findings demonstrate that the suggested technique for treating liver cancer with a dual-response nanocarrier based on mPEG-αPLA copolymer is promising.