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. 2022 Nov 19;20(1):490.
doi: 10.1186/s12951-022-01694-1.

Lactic acid modified rare earth-based nanomaterials for enhanced radiation therapy by disturbing the glycolysis

Hu Liu  1   2 , Han Wang  3 , Dalong Ni  4 , Youjia Xu  5   6
Affiliations

Lactic acid modified rare earth-based nanomaterials for enhanced radiation therapy by disturbing the glycolysis

Hu Liu et al. J Nanobiotechnology. .

Abstract

Deficient deposition of X-rays and strong capacity of repairing damage DNA of cancer cells limit the effect of radiation therapy (RT). Herein, we synthesize CsLu2F7 nanoparticles with lactic acid (LA) ligands (CsLu2F7-LA) to overcome these limitations. The high-Z atoms of Lu and Cs can deposit more X-rays for generating enhanced hydroxyl radicals (·OH). Meanwhile, the LA ligand will guide CsLu2F7-LA to target monocarboxylic acid transporter (MCT) and impede the transportation of free LA, leading to decreased glycolysis and DNA damage repair. Consequently, the curative effect of RT will be enhanced and the strategy of LA accumulation induced radiosensitization is proved by in vivo and in vitro experiments, which will bring prospects for enhanced RT with nanomedicine.

Keywords: Glycolysis; Lactic acid; Nanomedicine; Radiation therapy; Rare earth.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Illustration of a synthetic procedure of CsLu2F7-LA and b the mechanism that CsLu2F7-LA enhance the effect of RT
Fig. 2
Fig. 2
Characterization of nanomaterials. a TEM image of CsLu2F7-OA. b TEM image of CsLu2F7-LA. c HAADF image of CsLu2F7-LA. d Cs, e Lu and f F Elements mapping of CsLu2F7-LA. g EDS spectrum of CsLu2F7-LA. h XPS spectrum of CsLu2F7-LA. i XRD pattern of CsLu2F7-OA and CsLu2F7-LA
Fig. 3
Fig. 3
Experiments in vitro. a 143B cells viability of different concentrations of LA (n = 6, mean ± SD). b HUVEC cells viability of different concentrations of CsLu2F7-LA (n = 6, mean ± SD). c 143B cells viability of different concentrations of CsLu2F7-LA (n = 6, mean ± SD). d 143B cell pH staining of control group and CsLu2F7-LA group. Scale bar: 50 μm. e Relative intensity of BCECF in control group and CsLu2F7-LA group (n = 3, mean ± SD). f Relative content of ATP in control group and CsLu2F7-LA group (n = 3, mean ± SD). Two asterisks indicate P < 0.01, three asterisks indicate P < 0.001, and four asterisks indicate P < 0.0001 according to Student’s two-tailed t-test
Fig. 4
Fig. 4
Experiments in vitro. a Survival fraction of cell colony formation assay (n = 3, mean ± SD, single asterisk indicates P < 0.05 according to Student’s two-tailed t-test). b Photographs of cell colony formation assay. c Relative intensity of PI in each group (n = 3, mean ± SD, two asterisks indicate P < 0.01 according to Student’s two-tailed t-test). d Calcein-AM and PI staining of each group. e The yield of ·OH of each group measured by 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) staining. f Cell γ-H2AX staining of each group. Scale bar: 100 μm
Fig. 5
Fig. 5
Experiments in vivo. a Illustration of the experimental design. b The weights of tumor-bearing mice of each group (6 Gy, n = 5, mean ± SD). c Relative tumor volume of each group (6 Gy, n = 5, mean ± SD, triple asterisks indicate P < 0.001 according to Student’s two tailed t-test). d H&E staining, Ki67 staining and TUNEL staining of tumor sections. Scale bar: 100 μm
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