Enhanced radiotherapy using photothermal therapy based on dual-sensitizer of gold nanoparticles with acid-induced aggregation

doi:10.1016/j.nano.2020.102241

Nanomedicine: Nanotechnology, Biology and Medicine

Volume 29, October 2020, 102241

https://doi.org/10.1016/j.nano.2020.102241 Get rights and content

Highlights

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A dual-sensitizer of RT and PTT based on a GNPs system with acid-induced aggregation was successfully developed to enhance anti-tumor effect.
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The enhanced DNA damage and inhibition of DNA repair have been successfully integrated by using a combination therapy of RT and mild PTT.
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The multi-modal imaging effect of GNPs was simultaneously improved as aggregation of GNPs system, thus showing an all-in-one system of imaging-guided enhanced combination therapy.

Abstract

The damaged DNA strands caused by radiotherapy (RT) can repair by themselves. A gold nanoparticles (GNPs) system with acid-induced aggregation was developed into a dual sensitizer owing to its high radioactive rays attenuation ability and enhanced photothermal heating efficiency after GNPs aggregation to achieve a combination therapy of RT and photothermal therapy (PTT). In this combination therapy, the formed GNP aggregates firstly showed a higher sensitize enhancement ratio (SER) value (1.52). Importantly, the self-repair of damaged DNA strands was inhibited by mild PTT through down-regulating the expression of DNA repair protein, thus resulting in a much higher SER value (1.68). Anti-tumor studies further demonstrated that this combination therapy exhibited ideal anti-tumor efficacy. Furthermore, the imaging signals of GNPs in computed tomography and photoacoustic were significantly improved following the GNPs aggregation. Therefore, a dual sensitizer with multimodal imaging was successfully developed and can be further applied as a new anti-tumor therapy.

Graphical Abstract

Based on a GNPs system with acid-induced aggregation as a dual sensitizer, a combination therapy of RT and PTT from DNA level was successfully integrated by enhancing DNA damage and inhibiting DNA repair.

Section snippets

Materials

HAuCl₄·3H₂O was purchased from the Sigma Aldrich (USA). 2,3-Dimethylmaleic anhydride (DA) was provided by J&K Scientific Ltd. (Beijing, China). Peptide A (DDDDDC) and peptide B (KGGKGGKC) were obtained from GL Biochem Ltd. (Shanghai, China). mPEG2000-SH was provided by Yare Biotech (Shanghai, China).

Preparation and characterization of the GNPs system

The GNPs system was synthesized as in our previous studies.⁴⁰ Briefly, 200 mg of peptide B (KGGKGGKC) and 412 mg of 2,3-dimethylmaleic anhydride (DA) were co-dissolved in PBS (pH 8.0) and slowly

Characterization of the GNPs system

We first prepared the GNPs system as described in our previous studies. As shown in Figure 1, A-C, GNPs system exhibited a particulate structure under TEM and a diameter of ~40 nm, as shown by DLS. The size and UV–vis spectrum of the GNPs system remained unchanged after their incubation at pH 7.4 for 30 min. In contrast, in the acidic tumor environment (pH 6.5), the GNPs-B of the GNPs system suffered from a charge reversion from negative to positive owing to the DA fell off from peptide B, and

Discussion

Although there are many new anti-tumor strategies, such as photodynamic therapy⁴⁵^,⁴⁶ and photothermal therapy,⁴⁷^,⁴⁸ the radiotherapy (RT) can not be ignored in the clinical application.⁴⁹^,⁵⁰ Therefore, it is much necessary to improve the anti-tumor efficiency of RT, and its adverse effect for healthy tissues could not be ignored. In our previous study, the GNPs system with pH induced aggregation showed a preferable tumor retention and much higher radiosensitization under a γ ray radiation.⁴⁰

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: There are no conflicts of interest pertinent to the development of manuscript.

: Acknowledgments: This work was supported by the National Natural Science Foundation of China (51703247, 81722026, 51603231), the National Science Fund for Distinguished Young Scholars of Tianjin (18JCJQJC47300), the CAMS Innovation Fund for Medical Sciences (2016-I2M-3-022), the PUMC Youth Fund and the Fundamental Research Funds for the Central Universities (3332015100, 2018RC350016, 3332018115), and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT35031).

¹: These authors contributed equally to this work.

View full text

Enhanced radiotherapy using photothermal therapy based on dual-sensitizer of gold nanoparticles with acid-induced aggregation

Highlights

Abstract

Graphical Abstract

Section snippets

Materials

Preparation and characterization of the GNPs system

Characterization of the GNPs system

Discussion

Cancer Treat Rev

Mol Cell

Int J Radiat Oncol Biol Phys

Cancer Lett

Eur J Cancer

Biomaterials

Biomaterials

Cancer Radiother

Biomaterials

Trends Pharmacol Sci

Biomaterials

J Hematol Oncol

J Pharmacol Sci

Pancreatology

Biochem Biophys Res Commun

Adv Drug Deliv Rev

Biomaterials

DNA damage in cancer therapeutics: a boon or a curse?

Cancer Res

Sensitization of cancer cells to radiation and topoisomerase I inhibitor camptothecin using inhibitors of PARP and other signaling molecules

Cancers (Basel)

Protective effect of antrodia cinnamomea extract against irradiation-induced acute hepatitis

Int J Mol Sci

Establishment and characterization of a radiation-induced dermatitis rat model

J Cell Mol Med

The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence

Nat Rev Cancer

Molecular pathways: overcoming radiation resistance by targeting DNA damage response pathways

Clin Cancer Res

Sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway

Tumour Biol

Sodium glycididazole enhances the efficacy of combined iodine-125 seed implantation and chemotherapy in patients with non small-cell lung cancer

Oncol Lett

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ACS Nano

PEGylated Au@Pt nanodendrites as novel theranostic agents for computed tomography imaging and photothermal/radiation synergistic therapy

ACS Appl Mater Interfaces