Nanoscale Metal-Organic Frameworks for Phototherapy of Cancer

Abstract

Phototherapy involves the irradiation of tissues with light, and is commonly implemented in the forms of photodynamic therapy (PDT) and photothermal therapy (PTT). Photosensitizers (PSs) are often needed to improve the efficacy and selectivity of phototherapy via enhanced singlet oxygen generation in PDT and photothermal responses in PTT. In both cases, efficient and selective delivery of PSs to the diseased tissues is of paramount importance. Nanoscale metal-organic frameworks (nMOFs), a new class of hybrid materials built from metal connecting points and bridging ligands, have been examined as nanocarriers for drug delivery due to their compositional and structural tunability, highly porous structures, and good biocompatibility. This review summarizes recent advances on using nMOFs as nanoparticle PSs for applications in PDT and PTT.

Keywords: Metal-organic framework; Nanophotosensitizers; Photodynamic therapy; Photothermal therapy.

Fig. 1

(a) TEM image and (b) high-resolution TEM image of DBP-Hf. (c) Singlet oxygen generation of DBP-Hf, H₂DBP, and H₂DBP+HfCl₄ with SOSG assay. (d) In vitro PDT cytotoxicity of DBP-Hf and H₂DBP. (e) In vivo tumor growth inhibition curve of DBP-Hf and H₂DBP. Black and red arrows refer to the time of injection and light irradiation, respectively. Reprinted with permission form ref. [127]. Copyright 2014 American Chemical Society.

Fig. 2

(a) TEM image of DBC-Hf. Uv-vis spectra (b) and singlet oxygen generation (c) of DBC-Hf, DBP-Hf, H₂DBC and H₂DBP. Tumor growth inhibition curves after PDT treatment in CT26 (e) and HT29 (f) models. Red arrows refer to the time of light irradiation. Reprinted with permission form ref. [128]. Copyright 2015 American Chemical Society.

Fig. 3

(a) Schematic presentation of singlet oxygen generation by Hf-TCPP-PEG. (b) TEM image of Hf-TCPP. (c) Blood circulation of Hf-TCPP-PEG in healthy mice. (d) Biodistribution of Hf-TCPP-PEG in 4T1 tumor-bearing mice at 12 h post injection. Reprinted with permission form ref. [131]. Copyright 2016 Elsevier Ltd.

Fig. 4

(a) TEM images of PCN-224 with different sizes. (b) In vitro PDT cytotoxicity efficacy of different sized PCN-224. (c) In vitro PDT cytotoxicity efficacy of pristine PCN-224 and 1/4FA-PCN-224 in HeLa cells. Reprinted with permission form ref. [134]. Copyright 2016 American Chemical Society.

Fig. 5

Proposed mechanism of energy transfer in SO-PCN and illustration of switching operation in SO-PCN. Reprinted with permission form ref. [130]. Copyright 2015 Wiley.

Fig. 6

(a) Proposed mechanism of synthesis of UiO-PDT. (b) Singlet oxygen generation of UiO-PDT and I2-BDP with DPBF assay. (c) In vitro PDT cytotoxicity efficacy of UiO-PDT and I2-BDP in B16F10 cells. Reprinted with permission of ref. [135]. Copyright 2016 Royal Society of Chemistry.

Fig. 7

(a) Schematic presentation of combined PDT and immunotherapy by IDOi@TBC-Hf. Tumor inhibition curves for treated (b, d) and untreated (c, e) tumors of CT26 (b, c) or MC38 (d, e) models after PDT treatment. Black and red arrows refer to the time of injection and light irradiation, respectively. Reprinted with permission form ref. [129]. Copyright 2016 American Chemical Society.

Fig. 8

(a) Schematic figures of drug loading and EPR targeting strategy. (b) pH-responsive outer MOFs for drug release and dual-modal optical- and MRI-guided cancer therapy in vitro and in vivo. (c) MRI T₂ images of lung, liver and tumor before, 30 min and 24 h after intravenous injection of d-MOFs. d) Tumor growth curves after treatments. Reprinted with permission of ref. [150]. Copyright 2016 Elsevier Ltd.

Fig. 9

Schematic fugure of the synthetic strategy for PPy@MIL-100(Fe) as pH/NIR-responsive drug carriers for MRI/PAI dual-modality imaging and PTT/chemo synergistic therapy. Reprinted with permission of ref. [143]. Copyright 2016 Royal Society of Chemistry.

Fig. 10

(a) Fluorescent imaging of tumor-bearing mice before and after intravenous injection of Fe₃O₄@C@PMOF. The red arrow points to liver region and the yellow arrow points to tumor region. (b) MRI T₂ images of tumor-bearing mice. (c) Tumor growth curves after treatment. V₀ and V refer to tumor volumes before and after PTT and/or PDT treatment with Fe₃O₄@C@PMOF. Black and red arrows refer to injection and irradiation time points, respectively. (d) Representative optical images of tumor-bearing mice after treatments. Reprinted with permission of ref. [138]. Copyright 2017 Nature Publishing Group.