Combination therapy is considered to be a promising strategy for improving the therapeutic efficiency of cancer treatment. In this study, an on-demand pH-sensitive nanocluster (NC) system was prepared by the encapsulation of gold nanorods (AuNR) and doxorubicin (DOX) by a pH-sensitive polymer, poly(aspartic acid-graft-imidazole)-PEG, to enhance the therapeutic effect of chemotherapy and photothermal therapy. At pH 6.5, the NC systems formed aggregated structures and released higher drug amounts while sustaining a stable nano-assembly, structured with less systemic toxicity at pH 7.4. The NC could also increase antitumor efficacy as a result of improved accumulation and release of DOX from the NC system at pHex and pHen with locally applied near-infrared light. Therefore, an NC system would be a potent strategy for on-demand combination treatment to target tumors with less systemic toxicity and an improved therapeutic effect.
