Core-shell metal-organic frameworks with fluorescence switch to trigger an enhanced photodynamic therapy

Abstract

The design of hybrid metal-organic framework (MOF) nanomaterials by integrating inorganic nanoparticle into MOF (NP@MOF) has demonstrated outstanding potential for obtaining enhanced, collective, and extended novel physiochemical properties. However, the reverse structure of MOF-integrated inorganic nanoparticle (MOF@NP) with multifunction has rarely been reported. Methods: We developed a facile in-situ growth method to integrate MOF nanoparticle into inorganic nanomaterial and designed a fluorescence switch to trigger enhanced photodynamic therapy. The influence of "switch" on the photodynamic activity was studied in vitro. The in vivo mice with tumor model was applied to evaluate the "switch"-triggered enhanced photodynamic therapy efficacy. Results: A core-satellites structure with fluorescence off and on function was obtained when growing MnO₂ on the surface of fluorescent zeolitic imidazolate framework (ZIF-8) nanoparticles. Furthermore, A core-shell structure with photodynamic activity off and on function was achieved by growing MnO₂ on the surface of porphyrinic ZrMOF nanoparticles (ZrMOF@MnO₂). Both the fluorescence and photodynamic activities can be turned off by MnO₂ and turned on by GSH. The GSH-responsive activation of photodynamic activity of ZrMOF@MnO₂ significantly depleted the intracellular GSH via a MnO₂ reduction reaction, thus triggering an enhanced photodynamic therapy efficacy. Finally, the GSH-reduced Mn²⁺ provided a platform for magnetic resonance imaging-guided tumor therapy. Conclusion: This work highlights the impact of inorganic nanomaterial on the MOF properties and provides insight to the rational design of multifunctional MOF-inorganic nanomaterial complexes.

Keywords: Core-shell structure; Fluorescence switch; Metal-organic frameworks; Photodynamic therapy.

Figure 1

Illustration of the in-situ growth method to integrate MOF into inorganic nanomaterials and intracellular GSH-responsive activation of photodynamic activity of ZrMOF@MnO₂ hybrid nanoparticles for MRI-guided enhanced tumor therapy.

Figure 2

ZIF-FITC@MnO₂ core satellites structure with fluorescence off and on function. (A) TEM of FITC-encapsulated ZIF-8 nanoparticles. (B) TEM of ZIF-FITC@MnO₂ core satellites nanoparticles. (C) Digital picture of color change after in situ growth of MnO₂ on ZIF-FITC and GSH reduction. (D) Fluorescence turn off by MnO₂ nanodots and turn on by GSH.

Figure 3

(A) HAADF-STEM of ZrMOF@MnO₂. (B) HAADF-STEM image of area of interest used for element mapping. (C) Mn element map. (D) Zr element map. (E) Mn and Zr composite element map. (F) Sum EDS spectrum of area used for element mapping. (G) Dynamic light scattering of ZrMOF nanoparticles before and after integrating into MnO₂.

Figure 4

(A) UV-vis of ZrMOF, ZrMOF@MnO₂, and GSH treated ZrMOF@MnO₂. (B) Digital picture of GSH responsive ZrMOF@MnO₂. (C) Fluorescence of ZrMOF, ZrMOF@MnO₂, and GSH treated ZrMOF@MnO₂. (D) Singlet oxygen generation of ZrMOF. (E) Singlet oxygen generation of ZrMOF@MnO₂. (F) Singlet oxygen generation of GSH treated ZrMOF@MnO₂. To measure the singlet oxygen generation, nanoparticles were irradiated with 650 nm laser (200 mW/cm²). (G) LC-MS of GSH and GSSG from GSH oxidized by ZrMOF@MnO₂ hybrid nanoparticles.

Figure 5

Singlet oxygen generation of ZrMOF (top) and ZrMOF@MnO₂ (bottom) with different concentration of GSH. Black: background of singlet oxygen after adding SOSG; red: singlet oxygen generated after 15 min laser irradiation; blue: singlet oxygen generation after adding GSH; pink: generated singlet oxygen after a second 15 min laser irradiation.

Figure 6

(A) The summary of GSH effect on the generation of singlet oxygen of ZrMOF and ZrMOF@MnO₂ under irradiation of 650 nm laser (200 mW/cm²). (B) The release behavior of Mn from ZrMOF@MnO₂ under different conditions. (C) The r₁ value of ZrMOF@MnO₂ hybrid nanoparticles with and without GSH. (D) T₁-weighted images of mice at different times after intravenous injection with PEGylated ZrMOF@MnO₂ hybrid nanoparticles.

Figure 7

(A) Cell viability of U87MG cells with different treatments. (B) The curves of tumor growth after various treatments. (C) Survival rate of mice with U87MG tumor after various treatments. (D) The images of H&E stained tumor sections after various treatments.