Anti‐cancer combination therapy by co‐delivery of hydrophilic and hydrophobic using dual temperature and pH‐responsive liposomes

Abstract

A novel combination chemotherapic strategy by co-delivery of doxorubicin (DOX) and mitomycin C (MC) anti-cancers was reported using dual pH and temperature-responsive copolymer-modified liposomes to achieve superior therapeutic efficacy. The copolymer was prepared using temperature-responsive N-isopropylacrylamide and pH-responsive poly-acrylic acid monomers through reversible addition–fragmentation chain transfer polymerisation and revealed dual pH/temperature-dependent phase transitions proved by differential scanning colorimetric and cloud point measurements. With relatively high encapsulation efficiency of 81.2% for DOX and 77.3% for MC, the prepared polymer-modified responsive liposomes (PMRLs) have shown enhanced and controlled temperature/pH-dependent release profiles and significantly lower thermal dose thresholds with up to a 250-fold decrease at pH 7.4 and 1000-fold decrease at pH 5.5 compared to the traditional formulations. The temperature/pH-dependent release profile of the drugs was investigated in vitro and cytotoxicity of the carriers was evaluated using both normal and cancerous cell lines. It was found that the two drugs co-loaded PMRLs were revealed synergistic effects on cytotoxicity of the carriers against Michigan Cancer Foundation-7 breast cancer cells. The results revealed that by this combinational regimen, the prepared liposomes have the potential to dramatically decrease the risk of damage to healthy tissues normally caused by liposomal cancer therapy.