A novel pH sensitive theranostic PLGA nanoparticle for boron neutron capture therapy in mesothelioma treatment

Our plain-English summary of A novel pH sensitive theranostic PLGA nanoparticle for boron neutron capture therapy in mesothelioma treatment, by J. Sforzi, A. Lanfranco, R. Stefania, et al (Scientific Reports, 2023).

The study

• Authors: J. Sforzi, A. Lanfranco, R. Stefania, D. Alberti, V. Bitonto, S. Parisotto, P. Renzi, N. Protti, S. Altieri, A. Deagostino, S. Geninatti Crich
• Journal: Scientific Reports
• Published: 2023;13(1):620
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This study aims to develop poly lactic-co-glycolic acid (PLGA) nanoparticles with an innovative imaging-guided approach based on Boron Neutron Capture Therapy for the treatment of mesothelioma. The herein-reported results demonstrate that PLGA nanoparticles incorporating oligo-histidine chains and the dual Gd/B theranostic agent AT101 can successfully be exploited to deliver a therapeutic dose of boron to mesothelioma cells, significantly higher than in healthy mesothelial cells as assessed by ICP-MS and MRI. The selective release is pH responsive taking advantage of the slightly acidic pH of the tumour extracellular environment and triggered by the protonation of imidazole groups of histidine. After irradiation with thermal neutrons, tumoral and healthy cells survival and clonogenic ability were evaluated. Obtained results appear very promising, providing patients affected by this rare disease with an improved therapeutic option, exploiting PLGA nanoparticles.

© 2023. The Author(s).

In plain English

This was a laboratory study in cell cultures. It did not study people or asbestos exposure. The authors made biodegradable nanoparticles (PLGA) carrying AT101, a compound containing boron and gadolinium (used for MRI). One version, PLGA-His, carried histidine chains designed to release its load in slightly acidic conditions like those around tumours. A comparison version, PLGA-CTRL, did not. At pH 6.0, PLGA-His released 10% of AT101 after 24 hours and 30% after 72 hours. Mouse mesothelioma cells (AB22) and healthy human mesothelial cells (MeT-5A) were treated with the particles, then irradiated with thermal neutrons. The calculated maximum boron in AB22 cells was 62.8 ± 12.0 ppm with PLGA-His and 30.6 ± 8.6 ppm with PLGA-CTRL. In MeT-5A cells it was 5.0 ± 0.17 and 4.3 ± 0.8 ppm. After irradiation, compared with irradiated untreated cells, 60% of AB22 cells given PLGA-His and 30% given PLGA-CTRL died. MeT-5A cell counts showed no significant decrease 24 hours after irradiation, and their colony formation at 18 days was only slightly reduced. The authors proposed this boron neutron capture therapy approach as a possible alternative strategy to treat mesothelioma.

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 (in vitro) cell-culture experiment: nanoparticles were developed and tested, and the cells were then irradiated with thermal neutrons (boron neutron capture therapy)
• Who was studied: Two cell lines: AB22 murine (mouse) mesothelioma cells and MeT-5A human healthy mesothelial cells. No human or animal subjects.
• Exposure: No asbestos exposure was studied. Cells were treated for 24 h with PLGA-CTRL or PLGA-His nanoparticles carrying the gadolinium/boron agent AT101 (97 micromolar gadolinium and 970 micromolar boron), then irradiated with thermal neutrons.
• Main results:
  • Only at pH 6 was a significant AT101 release observed. According to Table 3, PLGA-His at pH 6.0 released 10% at 24 h and 30% at 72 h, versus 3% and 6% at pH 7.4. PLGA-CTRL released 2 to 4%.
  • Calculated maximum boron taken up (Table 4): AB22 mesothelioma cells 30.6 ± 8.6 ppm with PLGA-CTRL and 62.8 ± 12.0 ppm with PLGA-His. MeT-5A healthy cells 4.3 ± 0.8 ppm with PLGA-CTRL and 5.0 ± 0.17 ppm with PLGA-His. The calculation assumed a cell density of about 10 to the 8th cells per cubic centimetre.
  • MRI images of cell pellets suggested greater uptake of PLGA-His in mesothelioma cells than in healthy cells, and than with PLGA-CTRL.
  • In AB22 mesothelioma cells, 24 h after irradiation and compared with irradiated untreated control cells, 30% of cells treated with PLGA-CTRL died and 60% of cells treated with PLGA-His died.
  • MeT-5A healthy mesothelial cells showed no significant decrease in cell number 24 h after irradiation.
  • In the clonogenic assay 18 days after irradiation, AB22 cells stopped forming colonies, particularly when treated with PLGA-His.
  • In the same clonogenic assay, MeT-5A healthy cells showed only slightly reduced colony formation compared with irradiated untreated control cells.
• The authors' conclusion: The authors concluded that the nanoparticles were preferentially taken up by mesothelioma cells rather than healthy mesothelial cells. They proposed boron neutron capture therapy as a possible alternative therapeutic strategy to treat mesothelioma.
• Limitations the authors state:
  • The histidine signal intended to report on particle integrity (the quadrupolar peak) could not be detected in the PLGA-His particles used, because the gadolinium in them dominated the measurement.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Mesothelial Cells.

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