In-vitro evaluation of a multimodal pH-activatable nanoprobe for synergistic dual-drug delivery in tumor-targeted therapy

A smart drug delivery system (DDs) based on PEGylated (polyethylene glycol) gold/zinc oxide (PEG-Au/ZnO) loaded with doxorubicin (DOX) and chlorine-e6 (Ce6) was successfully synthesized, characterized, and evaluated against breast malignancy. With and without laser exposure, the DOX-PEG-Au/ZnO–Ce6 nanoprobe bypassed the internal barriers and exhibited much higher synergistic therapeutic activity than Ce6 and DOX alone. The controlled release kinetics of DOX in combination with Ce6 could inhibit tumor growth and remarkably enhance the sensitivity of chemotherapy. Apart from the chemotherapeutic effect, the residual PEG-Au/ZnO could amplify the reactive oxygen species (ROS) generation through cascade reactions, which will benefit the release of free zinc ions in the lysosome of inflammatory cells. Taken together, the as-prepared DOX-PEG-Au/ZnO–Ce6 nanoprobe is expected to facilitate the management of chemo-photodynamic combination therapy as Trojan horses to eliminate cancer and improve the quality of life for the patient by reducing acute toxic side effects.