Reduction and pH dual-sensitive nanovesicles co-delivering doxorubicin and gefitinib for effective tumor therapy

Owing to the complexity of tumorgenesis, combination therapy has proven to be a viable strategy for cancer treatment in recent years. However, the delivery and site-specific release of different therapeutic agents remain a major challenge in combination therapy. In this study, a polymeric nanovesicle based on a copolymer of polyethylene glycol and a polypeptide derivative was introduced as a vector to simultaneously deliver hydrophobic gefitinib and hydrophilic doxorubicin hydrochloride for multi-target combination therapy. The vesicle incorporating the two drugs exhibited prominent pH/reduction sensitivities to trigger the release of gefitinib and doxorubicin inside cancer cells. The two drugs co-delivered by the polymeric nanovesicle exhibited a joint anticancer effect both in vitro and in vivo. In particular, a remarkable therapeutic effect was demonstrated in animal studies using a mouse N2a neuroblastoma model. This study reveals the potential of reduction and pH dual-responsive nanovesicles bearing gefitinib and doxorubicin as an effective nano-medicine for cancer treatment.