2D LDH-MoS2 clay nanosheets: synthesis, catalase-mimic capacity, and imaging-guided tumor photo-therapy

Abstract

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg-Mn-Al layered double hydroxides (LDH) clay with MoS₂ doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS₂ and imaging and catalytic functions of Mg-Mn-Al LDH. The designed LDH-MoS₂ (LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg-Mn-Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H₂O₂ in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.

Keywords: Catalysis; Chlorin e6; LDH; MoS2; Tumor therapy.

Scheme 1

Schematic illustration of the hydrothermal synthesis with BSA coating and Ce6 loading and the synergistic tumor photo-therapy procedure of LMM@BSA/Ce6 nanosheets simultaneously including catalase-mimic and imaging-guided capacity

Fig. 1

a SEM of LMM nanosheets; b TEM of LMM@BSA nanosheets; c photographic image of typical Tyndall phenomenon of LMM@BSA clay nanosheets in water (left), saline (middle), and DMEM (right); d–i Al, Mg, Mo, Mn, O and S elemental distribution mappings of LMM nanosheets

Fig. 2

a XPS spectrum of Mn 2p; b XRD patterns of LDH, LDH-MoS_2, and LMM nanosheets; c FTIR spectra of LDH, LMM, and LMM@BSA nanosheets; d TG curves of LDH, LMM_, and LMM@BSA nanosheets

Fig. 3

a Light absorption of LMM@BSA clay nanosheets solution; b the photograph of the experimental appliance; c distilled water and concentration-dependent temperature profiles of LMM@BSA clay nanosheets (NIR laser: 1 W/cm²); d corresponding thermal imaging of c; e power density-dependent temperature profiles of LMM@BSA clay nanosheets solution; f corresponding thermal imaging of e; g time constant for heat transfer of LMM@BSA clay nanosheets; h steady-state heating curve of LMM@BSA clay nanosheets and distilled water and i recycling heating profiles of LMM@BSA clay nanosheets. The unit of bar in d and f is °C

Fig. 4

a The Ce6 loading efficiency of LMM@BSA clay nanosheets with different concentrations; b the DO content (mg/L) of dissolved oxygen in LMM@BSA and LMM@BSA + H₂O₂ solution; c, d absorption spectrum changes of DPBF under 660 nm laser irradiation with LMM@BSA/Ce6 nanosheets c in the absence and d presence of H₂O₂ (10 mM); e viability profile of HT29 cells after different treatments; f in vitro cumulative release profiles of DOX from LMM@BSA/DOX nanosheets under different pH and temperature; g–i the calcein-AM/PI dyeing morphology of HT29 cells corresponding to e; g LMM@BSA + PTT; h LMM@BSA/Ce6 + PDT; i LMM@BSA/Ce6 + PDT + PTT

Fig. 5

a The relative body weight changes of KM mice treated with saline and LMM@BSA clay nanosheets (n = 3); b long-term Mn bio-distribution of mice injected with LMM@BSA/Ce6 nanosheets; c, d serum biochemistry assay of mice injected with saline (control) and LMM@BSA dispersion and fed for different days. TB total bilirubin, CREA creatinine, ALT alanine transaminase, AST amino-transferase; e H&E-dyed tissue sections of major organs of KM mice that were injected with saline (control) or LMM@BSA clay nanosheets and fed for 14 days (scale bar = 100 μm)

Fig. 6

a In vitro brightness intensity of LMM@BSA in a mildly acidic environment (pH = 5.0), distilled water or GSH aqueous solutions after soaking at 37 °C for 2 h; b T₁-weighted MR imaging of solution corresponding to a, unit: mg/mL; c in vivo relative brightness intensity of mice tumor after I.T. or I.V. injected with saline and LMM@BSA; d–f in vivo T₁-weighted MR imaging corresponded to c, (d control, e I.V., and f I.T.)

Fig. 7

a The tumor heating curves of mice under NIR laser irradiation; b tumor growth profile of mice after various treatments as noted; c in vivo thermal imaging of mice after laser irradiation for different time points corresponding to a; d pictures of HT29 tumor-bearing mice at day 0 and day 28 corresponding to b. The unit of the bar in c: °C