Functionalized Scintillating Nanotubes for Simultaneous Radio- and Photodynamic Therapy of Cancer

Our plain-English summary of Functionalized Scintillating Nanotubes for Simultaneous Radio- and Photodynamic Therapy of Cancer, by I. Villa, C. Villa, R. Crapanzano, et al (ACS Applied Materials & Interfaces, 2021).

The study

• Authors: I. Villa, C. Villa, R. Crapanzano, V. Secchi, M. Tawfilas, E. Trombetta, L. Porretti, A. Brambilla, M. Campione, Y. Torrente, A. Vedda, A. Monguzzi
• Journal: ACS Applied Materials & Interfaces
• Published: 2021;13(11):12997-13008
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

As a model radio-photodynamic therapy (RPDT) agent, we developed a multicomponent nanomaterial by anchoring conjugated chromophores on the surface of scintillating chrysotile nanotubes. Its ultimate composition makes the system a scintillation-activated photosensitizer for the singlet oxygen production. This nanomaterial shows a remarkable ability to enhance the production of singlet oxygen in an aqueous environment, under X-ray irradiation, boosting its production by almost 1 order of magnitude. Its efficiency as a coadjutant for radiotherapy has been tested in vitro, showing a striking efficacy in enhancing both the prompt cytotoxicity of the ionizing radiation and the long-term cytotoxicity given by radiation-activated apoptosis. Notably, the beneficial activity of the RPDT agent is prominent at low levels of delivered doses comparable to the one employed in clinical treatments. This opens the possibility of effectively reducing the therapy exposure and consequently undesired collateral effects due to prolonged exposure of patients to high-energy radiation.

In plain English

In this laboratory study, the authors coated synthetic chrysotile nanotubes with light-activated dyes to boost X-ray radiotherapy by producing singlet oxygen, a reactive form of oxygen. Of three dyes tested, a porphyrin worked best. A version with lower porphyrin coverage, made from a 50 times lower starting dye concentration, plus a PEO polymer coating, raised singlet oxygen under X-rays by almost an order of magnitude over radiation acting on the test liquid alone. In glioblastoma (brain tumour) cells grown without X-rays, 20 micrograms of tubes per square centimetre changed cell numbers by under 5% versus untreated cells after 72 hours. At 40 and 60 micrograms per square centimetre, growth slowed, with untreated cultures 15 to 20% more populated. At 2 Gy, cells with tubes had a 500% enhancement in the fraction of dead cells versus cells irradiated without tubes, and a 97% loss of colony-forming ability. Without tubes, cells lost about 90% of colony-forming ability at 1 Gy, with no further change up to 8 Gy. The authors concluded that the tubes enhanced radiation's effects, especially at low doses.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory materials-development study with in vitro (cell culture) experiments
• Who was studied: Human primary glioblastoma cell line U-87, grown in culture dishes; no human or animal subjects
• Exposure: Synthetic chrysotile nanotubes made in the laboratory and coated with photosensitizer dyes (Erythrosine B, Rose Bengal or a porphyrin). The final version (NT-PEO-Por*) had lower porphyrin coverage, made from a 50 times lower starting porphyrin concentration, and a PEO coating. It was combined with soft X-ray doses of 0 to 12 Gy.
• Main results:
  • The optimized nanotubes (NT-PEO-Por*) increased singlet oxygen under X-rays by almost an order of magnitude compared with the amount produced by radiation interacting with the aqueous environment without nanotubes
  • At 20 μg per square centimetre of NT-PEO-Por*, the U-87 cell population changed by less than 5% compared with the unstained control after 72 hours of incubation (viability test without X-rays)
  • At 40 and 60 μg per square centimetre the nanotubes slowed growth of U-87 cells. The unstained control culture was 15 to 20% more populated after 72 hours.
  • At 2 Gy, nanotubes with PEO but no dye increased the number of dead cells by 150% compared with the unstained control sample, which was also irradiated
  • At 2 Gy, with NT-PEO-Por* staining, the fraction of dead cells was enhanced by 500% compared with the unstained irradiated control
  • In the MTT test, living cells stained with NT-PEO-Por* were reduced by 30 to 40% compared with unstained cells at 1 to 4 Gy
  • In flow cytometry of NT-PEO-Por*-stained cells, necrotic cells made up 11.9% at 1 Gy and 9.4% at 2 Gy
  • At 1 Gy, stained cells had twice as many apoptotic cells as the control sample (caspase assay)
  • Unstained cells exposed to 1 Gy lost about 90% of their colony-forming (proliferation) ability, with no further change up to 8 Gy
  • Cells treated with the nanotube agent lost 97% of their colony-forming ability at 2 Gy
• The authors' conclusion: The authors concluded that the functionalized nanotubes clearly enhanced the effect of X-ray exposure on the tumour cells, particularly at low doses comparable to clinical ones, and that the findings support future in vivo tests for brain tumours
• Limitations the authors state:
  • Rapid cell death left debris that could not be counted as exact cell numbers, adding uncertainty to the Trypan blue assay
  • The caspase (apoptosis) assay could not be done at doses above 2 Gy because too few non-necrotic cells survived
  • How dye molecules interact on the nanotube surfaces was not fully analysed and needs further study

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Chrysotile, Apoptosis.

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