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Review
. 2022 Nov 11;15(22):7977.
doi: 10.3390/ma15227977.

Biofunctional Layered Double Hydroxide Nanohybrids for Cancer Therapy

Joonghak Lee  1   2   3 , Hee Seung Seo  4   5 , Wooram Park  6   7 , Chun Gwon Park  4   5   8   9 , Yukwon Jeon  10 , Dae-Hwan Park  1   2   3
Affiliations
Review

Biofunctional Layered Double Hydroxide Nanohybrids for Cancer Therapy

Joonghak Lee et al. Materials (Basel). .

Abstract

Layered double hydroxides (LDHs) with two-dimensional nanostructure are inorganic materials that have attractive advantages such as biocompatibility, facile preparation, and high drug loading capacity for therapeutic bioapplications. Since the intercalation chemistry of DNA molecules into the LDH materials were reported, various LDH nanohybrids have been developed for biomedical drug delivery system. For these reasons, LDHs hybridized with numerous therapeutic agents have a significant role in cancer imaging and therapy with targeting functions. In this review, we summarized the recent advances in the preparation of LDH nanohybrids for cancer therapeutic strategies including gene therapy, chemotherapy, immunotherapy, and combination therapy.

Keywords: cancer therapy; drug delivery system; layered double hydroxide; nanohybrid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 3
Figure 3
(A) Gel retardation assay of siRNA nanohybrids with LDH and LDHFA; (B) SEM image of LDHFA/siRNA; (C) in vivo tumor growth inhibition rate and (D) image of anti-tumor effect of KB tumor-bearing mice treated with LDHFA/siRNA nanohybrids [35] (reproduced from Ref. [35] with permission from the WILEY-VCH Verlag GmbH & Co. KGaA) * p < 0.05, ** p < 0.01; (E) schematic illustration of strategy to synthesize siRNA-Mn-LDH; (F) XPS spectra of Mn 2p; (G) T1-weighted MR images; (H) positive-cell percentage of N2a cells internalizing CD-siRNA/LDH (**** p < 0.0001) [44] (reproduced from Ref. [44] with permission from the WILEY-VCH Verlag GmbH & Co. KGaA).
Figure 1
Figure 1
Overview of layered double hydroxide nanohybrids and strategies for therapeutic applications: (A) gene therapy; (B) chemotherapy; (C) immunotherapy; (D) combination therapy.
Figure 2
Figure 2
Various ways to prepare LDH nanohybrids for therapeutic application from top to bottom co-precipitation, ion exchange, surface functionalization, and exfoliation reassembling.
Figure 4
Figure 4
(A) X-ray diffraction (XRD) patterns; (B) high-resolution transmission electron microscopy (HR-TEM) images of MTX-LDH nanohybrid; (C) anti-tumor activity in the MCF7/mot orthotopic breast model * p < 0.05, ** p < 0.01; (D) survival rate of tumor-bearing mice; (E) histological and immunohistological analysis of tumor tissue sections from MCF-7/mot orthotopic tumor-bearing mice; (F) quantification of TUNEL-positive spots in tumor sections [46] (reproduced from Ref. [46] with permission from the Springer Nature Limited).
Figure 5
Figure 5
(A) X-ray diffraction (XRD) patterns; (B) scanning electron-microscopic (SEM) image of the Co@MTX-LDH; (C) Co k-edge X-ray adsorption spectroscopy (XAS), (D) and Fourier transform-extended X-ray absorption fine structure (FT-EXAFS) spectra; (E) SPECT/CT image of a tumor in mouse model after IV injection [31] (reproduced from Ref. [31] with permission from the WILEY-VCH Verlag GmbH & Co. KGaA).
Figure 6
Figure 6
(A) TEM images of the MgAl-LDH and DOX@MgAl−LDH; (B) release pattern of DOX from the DOX@MgAl−LDH in PBS with different pH values at 37 °C; (C) cell viability of the DOX@MgAl−LDH in HepG2 (D) and H22 cells; (E) tumor volume change in H22 tumor−bearing mice after IV administration of each sample; ** p < 0.01, *** p < 0.001. (F) in vivo Cy5 fluorescence images of H22 tumor−bearing mice at different time courses after IV injection [49] (reproduced from Ref. [49] with permission from the Royal Society of Chemistry).
Figure 7
Figure 7
(A) Particle size distribution, and (B) TEM image of Mg2Al-Cl-LDH; (C) OVA adsorption isotherm to MgAl-LDH [27] (reproduced from Ref. [27] with permission from Elsevier Ltd.); (D) SIINFEKL-specific IFN-γ secretion treated with each sample; (E) reduction in tumor growth treated with each sample * p < 0.05, ** p < 0.01, *** p < 0.001. (Two-way ANOVA with Tukey’s post-test); (F) percentage of survival mice with EG7-OVA lymphoma cells [63] (reproduced from Ref. [63] with permission from the Royal Society of Chemistry).
Figure 8
Figure 8
(A) XRD patterns of various size of LDH NPs; (B) FT-IR spectra of OVA-LDH NPs; (C) TEM images of different sizes of OC-LDH; (D) schematic illustration of behavior in terms of various sizes of CO-LDH; (E) the average volume of tumor after IV vaccinations; (F) secreted level of IFN-γ and (G) OVA-specific IgG1 (* p < 0.05, ** p < 0.01, *** p < 0.001) [65] (reproduced from Ref. [65] with permission from Springer Nature).
Figure 9
Figure 9
(A) XRD patterns of 5-FU/LDH nanohybrid; (B) TEM image of the siRNA-5-FU/LDH nanohybrid; (C) agarose gel retardation assay with various mass ratios of siRNA:LDH; (D) cytotoxicity to various concentration of LDHs to MCF-7 cell lines; (E) MTT assay analysis on the viability of MCF-7 cells at the 5-FU concentration ranging from 0 to 9.6 μg/mL and 40 nm concentration of CD-siRNA (* p < 0.01, ** p < 0.05, **** p < 0.0001); (F) expression levels of Bcl-2 against α-tubulin. Concentration of CD-siRNA was 2.4 μg/mL and 40 nm, and LDH concentration was 50 μm/mL, respectively [34] (reproduced from Ref. [34] with permission from Elsevier Ltd.).
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