Fig.1 TEM image and corresponding size distribution histogram of TPGS/Ppa nanomicelles(A), hydrodynamic size and PDI value of TPGS/Ppa nanomicelles measured by DLS(B), zeta potentials of TPGS and TPGS/Ppa(in PBS, pH 7.4)(C), UV⁃Vis absorption spectrum of TPGS/Ppa(in DMSO)(D), fluorescence emission spectrum(λex=608 nm) of TPGS/Ppa(in DMSO)(E), UV⁃Vis absorption spectra of Ppa(F) and TPGS/Ppa(G)(in PBS with 1% DMSO) under continuous laser irradiation(671 nm and 1 mW/cm2)

Fig.2 Relative viabilities of the 4T1 cells treated with different concentrations of TPGS, Ppa, or TPGS/Ppa for 24 h under dark(A) and laser conditions(660 nm, 2 mW/cm2, 2 min)(B); ROS levels of TPGS⁃, Ppa⁃, or TPGS/Ppa⁃treated 4T1 cells under laser condition(Ppa=0.5 μmol/L, laser: 660 nm, 2 mW/cm2, 1 min)(C); fluorescence intensities of the 4T1 cells incubated with Ppa(D) or TPGS/Ppa(E) for different periods as measured by flow cytometry; fluorescence intensity-time curves of the 4T1 cells incubated with Ppa or TPGS/Ppa for different periods(Ppa=2 μmol/L)(F); flow cytometric results of the 4T1 cells that were treated with culture medium(control), TPGS/Ppa+one endocytic inhibitor(amiloride, MβCD, genistein, or CPZ), or TPGS/Ppa under 4 ℃(G); and confocal fluorescence images of the 4T1 cells after incubation with Ppa or TPGS/Ppa(Ppa=2 μmol/L) for various periods as indicated(H)

Fig.3 Confocal fluorescence images of Ppa⁃ or TPGS/Ppa⁃treated 4T1 cells stained with ER⁃Tracker

Fig.4 Confocal fluorescence images of Ppa⁃ or TPGS/Ppa⁃treated 4T1 cells stained with LysoTracker

Fig.5 Confocal fluorescence images of Ppa⁃ or TPGS/Ppa⁃treated 4T1 cells stained with Rhod 123

Fig.6 Flow cytometric results of 4T1 cells after treatment with culture medium(control), Ppa, TPGS/Ppa, Ppa+laser, or TPGS/Ppa+laser(660 nm, 2 mW/cm2, 1 min)

Fig.7 Timeline of the in vivo therapeutic evaluation experiments(A), ex vivo fluorescence images of tumor tissues and major organs of the 4T1 tumor⁃bearing mice sacrificed before injection(control) and at different time points after i.v. injection with Ppa or TPGS/Ppa(Ppa=4 mg/kg)(B), experimental outline of various treatment steps for evaluating the anticancer efficiencies of different drugs in tumor⁃bearing mice(C), relative tumor volumes(D) and body weights of the tumor⁃bearing mice after different treatments(E),H&E⁃stained tissue slices of major organs(hearts, livers, spleens, lungs, and kidneys) and tumors of the mice sacrificed on the 20th day after treatment with PBS or “TPGS/Ppa+ laser”(F), TUNEL assay results of the tumor tissues collected from the mice after treatment with PBS or “TPGS/Ppa+laser”(G)（B） From top to bottom in each image： heart， liver， spleen， lung， kidneys， and tumor； （C） for phototherapy， 671 nm laser irradiation（15 mW/cm2， 15 min） was carried out at 1 d after i.v. injection of Ppa and TPGS/Ppa（Ppa=4 mg/kg）； （D） statistical significance was calculated via one⁃way analysis of variance（ANOVA） with a Tukey’s post⁃hoc test. The P values of less than 0.05 were considered significant. ***P < 0.001； ns： non⁃significant difference. （D， E） The statistical data were expressed as mean±standard deviation（n=3）.