Investigation of the Impact of L-Phenylalanine and L-Tyrosine Pre-Treatment on the Uptake of 4-Borono-L-Phenylalanine in Cancerous and Normal Cells Using an Analytical Approach Based on SC-ICP-MS

Sep 24, 2026

Uploaded by Stanley

Boron, especially its B-10 isotope, is central to medical research because thermal-neutron reactions generate ionizing particles that can eliminate cancer cells, supporting boron neutron capture therapy (BNCT). 4-Borono-L-phenylalanine (BPA) is promising for BNCT, and improving BPA uptake is pursued through L-amino acid preloading. This study applies ICP-MS and single-cell ICP-MS (SC-ICP-MS) to test L-tyrosine and L-phenylalanine preloading in A549 non-small cell lung carcinoma and V79-4 normal lung fibroblast models. L-tyrosine and L-phenylalanine increased BPA uptake in V79-4 by 2.04 ± 0.74 and 1.46 ± 0.06 folds, respectively, whereas A549 showed increased uptake only with L-tyrosine (1.24 ± 0.47). SC-ICP-MS revealed pronounced boron content heterogeneity in A549, including a high-uptake subpopulation, confirming cellular uptake variability. The findings validate SC-ICP-MS for precise cellular boron quantification.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Keywords

1. Introduction

Boron properties and BNCT rationale

BPA transport via LAT-1 and relevance to cancer

Need for in vitro uptake evaluation and retention challenges

Results and analytical approach (study focus)

molecules Article Investigation of the Impact of L-Phenylalanine and L-Tyrosine Pre-Treatment on the Uptake of 4-Borono-L-Phenylalanine in Cancerous and Normal Cells Using an Analytical Approach Based on SC-ICP-MS Emilia Balcer 1,2, Joanna Giebułtowicz 2, *, Małgorzata Sochacka 2, Anna Ruszczy ´nska 3, Magdalena Muszy ´nska 3,4 and Ewa Bulska 3 Citation: Balcer, E.; Giebułtowicz, J.; Sochacka, M.; Ruszczy ´nska, A.; Muszy ´nska, M.; Bulska, E. Investigation of the Impact of L-Phenylalanine and L-Tyrosine Pre-Treatment on the Uptake of 4-Borono-L-Phenylalanine in Cancerous and Normal Cells Using an Analytical Approach Based on SC-ICP-MS. Molecules 2023, 28, 6552 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules28186552 Academic Editors: Raﬁk Karaman, Paola Fossa and Jarkko Rautio Received: 21 August 2023 Revised: 4 September 2023 Accepted: 6 September 2023 Published: 10 September 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Radiochemistry Team, Reactor Research Division, Nuclear Facilities Operations Department, National Centre for Nuclear Research, Sołtana 7, ´Swierk, 05-400 Otwock, Poland; [emilia.balcer@ncbj.gov.pl](emilia.balcer@ncbj.gov.pl) 2 Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland; [malgorzata.bogucka@wum.edu.pl](malgorzata.bogucka@wum.edu.pl) 3 FacultyZwirki iofWChigeumryit0y,,B02i-o0log89icWaalransa,CPemlanicda;Rruesseazczrch@cCenhemtruew, Ueverpls(ityAoRf);Warsaw, [magdalena.muszynska@pepolska.pl](magdalena.muszynska@pepolska.pl) (M.M.); [ebulska@chem.uw.edu.pl](ebulska@chem.uw.edu.pl) (E.B.) 4 Pro-Environment Polska Sp. z o.o., Z˙ wirki i Wigury 101, 02-089 Warsaw, Poland * [Correspondence: joanna.giebultowicz@wum.edu.pl](Correspondence: joanna.giebultowicz@wum.edu.pl); Tel.: +48-22-5720630 Abstract: Boron has gained signiﬁcant attention in medical research due to its B-10 isotope's high cross section for the reaction with thermal neutrons, generating ionizing particles that can eliminate cancer cells, propelling the development of boron neutron capture therapy (BNCT) for cancer treatment. The compound 4-borono-L-phenylalanine (BPA) has exhibited potential in BNCT clinical trials. Enhancing BPA uptake in cells involves proposing L-amino acid preloading. This study introduces a novel analytical strategy utilizing ICP-MS and single cell ICP-MS (SC-ICP-MS) to assess the effectiveness of L-tyrosine and L-phenylalanine preloading on human non-small cell lung carcinoma (A549) and normal Chinese hamster lung ﬁbroblast (V79-4) models, an unexplored context. ICP-MS outcomes indicated that L-tyrosine and L-phenylalanine pre-treatment increased BPA uptake in V79-4 cells by 2.04 􀀆 0.74-fold (p = 0.000066) and 1.46 􀀆 0.06-fold (p = 0.000016), respectively. Conversely, A549 cells manifested heightened BPA uptake solely with L-tyrosine preloading, with a factor of 1.24 􀀆 0.47 (p = 0.028) . BPA uptake remained higher in A549 compared to V79-4 regardless of preloading. SC-ICP-MS measurements showcased noteworthy boron content heterogeneity within A549 cells, signifying diverse responses to BPA exposure, including a subset with notably high BPA uptake. This study underscores SC-ICP-MS's utility in precise cellular boron quantiﬁcation, validating cellular BPA uptake's heterogeneity. Keywords: 4-borono-L-phenylalanine; boron; boron neutron capture therapy; L-phenylalanine; L-tyrosine; single cell ICP-MS 1. Introduction Cancer is a complex and life-threatening disease characterized by uncontrolled cellular growth and division. Dev

FAQs

Why is boron important for cancer treatment in BNCT?

Boron-10 has a high cross section for reactions with thermal neutrons, producing ionizing particles that can kill cancer cells, which is the basis of BNCT.

How did L-tyrosine and L-phenylalanine pre-treatment affect BPA uptake?

In V79-4 cells, both L-tyrosine and L-phenylalanine pre-treatment increased BPA uptake, while in A549 cells increased uptake was observed only with L-tyrosine preloading.

What did single-cell ICP-MS reveal about BPA uptake in A549 cells?

Single-cell measurements showed notable heterogeneity in boron content, indicating varied cellular responses and identifying a subset of cells with notably high BPA uptake.

Sep 24, 2026

Uploaded by Stanley