pH-Triggered Conformational Change of Antp-Based Drug Delivery Platform for Tumor Treatment with Combined Photothermal Therapy and Chemotherapy.

Poor cellular uptake and low therapeutic efficacy of small-molecule antitumor drugs limit the application of drug delivery systems (DDSs) in cancer therapy. A conformational change of the Antp mimetic peptide (AMP) in tumor microenvironments can greatly increase the cellular uptake as well as control drug release from a DDS. In this study, AMP-based nanoparticles (AMP-NPs) conjugated with tyroserleutide (YSL), an immunologically therapeutic tripeptide, are designed to encapsulate doxorubicin (Dox) and indocyanine green (ICG) to improve cellular uptake and cancer therapeutic efficacy by combining chemotherapy with photothermal therapy. In vitro studies verify that AMP-NPs can control the release of Dox and YSL at different pH values. Cell experiments show that AMP-NPs can promote the cellular uptake of Dox, and YSL can promote hepatocarcinoma cell (H22) apoptosis through downregulating Bcl-2 and cyclin D1 expression. In a mouse xenograft model using H22 cells, tumors are ablated when Dox- and ICG-loaded AMP-NPs are injected with the combination of hyperthermia effect induced by near-infrared (NIR) laser irradiation and chemotherapy from Dox and YSL. The pH-, photothermal-, and glutathione-responsive AMP-NPs with a conformational transition strategy can be utilized to synergistically enhance the cancer therapeutic efficacy with few side effects upon NIR laser irradiation.