Green Tea Extract Assembled Nanoclusters for Combinational Photothermal and Chemotherapy

“Green chemistry” is a newly developed approach that uses natural products to fabricate drug delivery systems; it has many advantages, such as low cost, simplicity, rapidity and environmental friendliness. In this study, we fabricated doxorubicin-loaded gold nanoclusters via a “green chemistry” method, involving the use of green tea extract to realize combinational photothermal and chemotherapy against melanoma. Green tea extract acted as a reducing agent of chloroauric acid and a stabilizer of the nanoclusters, and it also provided a co-polymerization site for doxorubicin. Gold nanoclusters were formed in the presence of the reductive polyphenols in the green tea extract. The accordingly converted polyphenol oxides could assemble into oligomers to stabilize the formulated nanoclusters while co-polymerizing with doxorubicin through π–π stacking and electrostatic interactions. This drug delivery system showed good stability, pH-sensitive drug release properties and enhanced cellular uptake. In vitro and in vivo experiments both demonstrated that our system with combinational photothermal and chemotherapy could achieve significantly enhanced tumor growth inhibition compared to monotherapy. Overall, this platform may provide a safe and efficient strategy for cancer treatment and new insight into green, natural extracts for nanoparticle fabrication.