In vivo heart targeting and therapeutic effects of a mitochondrial-targeting nanotherapy TTPCD NP in mice. (A) Ex vivo fluorescence images (left) and quantitative analysis (right) of hearts isolated from mice after inhalation of Cy7.5/TPCD NP or Cy7.5/TTPCD NP. (B) The heart weight of different groups. (C) Ratios of HW/TL for mice with DOX-induced heart failure after treatment with TPCD NP or TTPCD NP at 25 mg/kg via inhalation. (D) Representative M-mode echocardiography images of mouse hearts after different treatments. (E-F) LVEF and LVFS quantified by echocardiography. (G-H) The levels of MDA (G) and H2O2 (H) in heart homogenates of mice treated with different formulations. The total protein content in heart homogenates was measured by the BCA assay. (I-J) Serum levels of cTnI (I) and CK (J). Data are mean ± SD (A, n = 3; B-C,E-J, n = 5). Statistical significance was assessed by the one-way ANOVA with post-hoc LSD tests. *P < 0.05, **P < 0.01, ***P < 0.001.