Metal-Organic Framework Nanoparticle-Based Biomineralization: A New Strategy toward Cancer Treatment

Abstract

Cancer treatment using functional proteins, DNA/RNA, or complex bio-entities is important in both preclinical and clinical studies. With the help of nano-delivery systems, these biomacromolecules can enrich cancer tissues to match the clinical requirements. Biomineralization via a self-assembly process has been widely applied to provide biomacromolecules exoskeletal-like protection for immune shielding and preservation of bioactivity. Advanced metal-organic framework nanoparticles (MOFs) are excellent supporting matrices due to the low toxicity of polycarboxylic acids and metals, high encapsulation efficiency, and moderate synthetic conditions. In this review, we study MOFs-based biomineralization for cancer treatment and summarize the unique properties of MOF hybrids. We also evaluate the outlook of potential cancer treatment applications for MOFs-based biomineralization. This strategy likely opens new research orientations for cancer theranostics.

Keywords: biomineralization; cancer treatment; metal-organic framework; theranostics.

Figure 1

MOFs-based biomineralization of proteins, enzymes, DNA/RNA and virus, and their applications in cancer treatment.

Figure 2

(A) Illustration of MOFs-based biomineralization and surface modification, and the intracellular delivery of MOF hybrid. (B) The cell fluorescence of BSA@MOF hybrid (a), FITC-BSA (b), BSA@MOF hybrid and early endosomes localized EER (c), BSA@MOF hybrid and lysosome localized LyR (d). (C) The study of the caspase 3/HSA@ MOF hybrid: (a) The cell fluorescence of HSA and caspase 3 co-encapsulated MOF hybrid. (b) The fluorescence intensity of control cells (1), HSA@MOF hybrid (2), caspase 3/HSA@ MOF hybrid 2 h (3) and 4 (4). (c)The cell viability after treatment with different MOF hybrids . Copyright 2018 American Chemical Society.

Figure 3

(A) Schematic illustration of the EMP nanoparticles and the application of the intracellular delivery system. (B) TEM images of MP (a), EVs (b), EVM (c), and EMP (d) nanoparticles, scale bars: 100 nm. (C) The flow cytometry analysis study of the bare protein (a), MP (b), EMP (c) and LMP (d) nanoparticles incubated MDA-MB-231 cells. (D) The tumor growth curves (a), body weight variation (b) after injected intravenously with PBS, gelonin, MP and EMP nanoparticles (n = 5). *P < 0.05, **P < 0.01. The MDA-MB-231 xenograft tumors images (c) and the weights (d) after different treatments . Copyright 2018 American Chemical Society.

Figure 4

(A) Schematic illustration of the TGZ@eM and the cancer starvation therapy; (B) the cell viability after treated with different nanoparticles; (C) the HIF-1α staining of MCTS after different treatments; (D) the fluorescence images of MCTS after treated with different nanoparticles ((1) PBS, (2) ZIF-8@eM, (3) GZ@eM, (4) TZ@eM, (5) TGZ@eM) . Copyright 2018 American Chemical Society.

Figure 5

(A) The preparation procedure of the multifunctional GOx-loaded ZIF-8 MOFs and the glucose-responsive degradation procedure. (B) SEM images of insulin/GOx@MOFs (II), MOFs after reacted with glucose (50 mM) for 1 h (III) and MOFs incubated in PBS (pH 7.4) for 2 days. (C) Glucose-induced release from the insulin/GOx@MOFs (a) and VEGF aptamer/GOx@MOFs (b) in the presence of glucose ((1) 0 mM, (2) 1 mM, (3) 5 mM, (4) 10 mM, (5) 50 mM); selective glucose-induced release from the insulin/GOx@MOFs (c) and VEGF aptamer/GOx@MOFs (d) in the presence of glucose (1), galactose (2), β-lactose (3), sucrose (4), pure buffer solution (5) . Copyright 2018 American Chemical Society.

Figure 6

(A) Biomimetic Cas9/sgRNA@MOF hybrid for genome editing: (a) schematic illustration of the Cas9/sgRNA encapsulated within ZIF-8; the Flow cytometry analysis (B) and qPCR quantitation (c) of different treatments 2 and 4 days . Copyright 2018 American Chemical Society.

Figure 7

The precise inclusion of single-stranded DNA using isoreticular MOFs: (A) the ssDNA transfection procedure of ssDNA@Ni-IRMOF-74-II; (B) the protection studies of ssDNA using different porous nanostructures in FBS; (C) the intracellular delivery of ssDNA using ssDNA@Ni-IRMOF-74-II and pure ssDNA; (D) gene silencing efficiency of MCF-7 cells for the DNAzyme delivery with Ni-IRMOF-74-II, Lipo, and Neofec . Copyright 2018 Nature.

Figure 8

The MOFs-based biomineralization of anaerobic bacteria: (A) the formation of the MOF (a), the M. thermoacetica-MOF wrapping cycle (b), the interface of the MOF and bacteria (c), the ROS response of the interface (d); (B) High-angle annular dark-field STEM image (a) and SEM image (b) of the prepared M. thermoacetica-MOF, EDS mapping of the M. thermoacetica-MOF ((c) C element, (d) S element, (e) P element, (f) Zr element); (C) PXRD pattern and Bragg position of M. thermoacetica-MOF, MOF soaked in culture media, MOF as-synthesized and MOF simulated; (D) The viability of M. thermoacetica and M. thermoacetica-MOF when treated with 5 μM (a), and 50 μM (b) H₂O₂ . Copyright 2018 National Academy of Sciences. The preparation of TMV@ZIF-8 nanocomposites: (E) the schematic illustration of the TMV@ZIF-8 rod-shaped nanocomposites; (F) the SEM of the TMV@ZIF-8 composites varying the reaction time. . Copyright 2018 American Chemical Society.

Figure 9

The potential encapsulation procedure (A) and the intracellular delivery (B) of OVs using MOF.