OICC Press Journal of Nanostructure in Chemistry 2193-8865 12 6 (December 2022) 2021 10 20 Bimetallic Au–Ag nanocages extended TPP conjugate structure for self-enhancing therapy of tumors 10.1007/s40097-021-00457-y EN Yilin Wen Pharmaceutical Engineering Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, CN Lu Chen Pharmaceutical Engineering Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, CN Feng Leng Pharmaceutical Engineering Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, CN Zhangyou Yang Pharmaceutical Engineering Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, CN Chao Yu Pharmaceutical Engineering Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, CN Journal Article 2021 10 20 Abstract Mitochondria are particularly sensitive to heat and also can be easily damaged by reactive oxygen species (ROS). However, due to the extremely complicated microenvironment in tumors, monotherapies targeting mitochondria often fail to achieve desired results. To solve this problem, we synthesized Au–Ag cages via electrical substitution reaction and linked mitochondrial-targeting molecular (4-carboxybutyl) triphenyl phosphonium bromide (TPP) to obtain multifunctional nanoplatforms TPP-PEG-Au–Ag cages (TPCs). The self-augmented photothermal therapy (PTT) combined with photodynamic therapy (PDT) achieved triple antitumor treatment. Due to the surface-enhanced Raman scattering between the bimetal and the extended conjugate structure of TPP, the photothermal conversion efficiency of TPCs reached 58.47% under 808 nm laser irradiation, which amounts to an increase of 9.25% compared to the pure Au–Ag cages. Moreover, Ag particles generate more ROS and O 2 through the Fenton reaction to enhance PDT treatment. Cell experiments show that the complementary self-enhancement model of TPCs-Ce6 has excellent anti-cancer effects through PDT/PTT under laser irradiation. Therefore, this work created a multifunctional nanometer agent that realizes a mitochondrial-targeted combination therapy for cancer. It also provides a new idea for improving the light-to-heat conversion efficiency of materials. Graphic abstract