Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles - Synthesis, Stability, and Tumor Inhibition Studies

Sep 22, 2026

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Boron neutron capture therapy (BNCT) targets invasive, radioresistant cancers but needs a selective boron-10 drug with high tumor delivery. This study evaluates boron-rich poly(ethylene glycol)-block-(poly(4-vinylphenyl boronate ester)) polymer micelles prepared by atom transfer radical polymerization for BNCT. TEM shows spherical micelles of 43 ± 10 nm with improved size and morphology after lyophilization and reconstitution. In vitro and in vivo results demonstrate markedly higher boron accumulation, improved tumor selectivity, and delayed tumor growth.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

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Abstract

Introduction

BNCT mechanism and boron-10 requirements

Approved BNCT boron compounds (BSH and BPA)

Rationale for third-generation boron agents

Polymer micelles as boron delivery carriers

This article is licensed under CC-BY 4.0 [pubs.acs.org/Biomac](pubs.acs.org/Biomac) Article Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles: Synthesis, Stability, and Tumor Inhibition Studies Wan Yun Fu, Yi-Lin Chiu, Shi-Chih Huang, Wei-Yuan Huang, Fang-Tzu Hsu, Han Yu Lee, Tzu-Wei Wang, and Pei Yuin Keng* Cite This: Biomacromolecules 2024, 25, 4215−4232 Read Online | | | | | | | | --- | --- | --- | --- | --- | --- | | ACCESS | Metrics & More | | Article Recommendations | | *sı Supporting Information | ABSTRACT: Boron neutron capture therapy (BNCT) targets invasive, radioresistant cancers but requires a selective and high B- 10 loading boron drug. This manuscript investigates boron-rich poly(ethylene glycol)-block-(poly(4-vinylphenyl boronate ester)) polymer micelles synthesized via atom transfer radical polymerization for their potential application in BNCT. Transmission electron microscopy (TEM) revealed spherical micelles with a uniform size of 43 ± 10 nm, ideal for drug delivery. Additionally, probe sonication proved effective in maintaining the micelles’ size and morphology postlyophilization and reconstitution. In vitro studies with B16−F10 melanoma cells demonstrated a 38-fold increase in boron accumulation compared to the borophenylala- nine drug for BNCT. In vivo studies in a B16−F10 tumor-bearing mouse model confirmed enhanced tumor selectivity and accumulation, with a tumor-to-blood (T/B) ratio of 2.5, surpassing BPA’s T/B ratio of 1.8. As a result, mice treated with these micelles experienced a significant delay in tumor growth, highlighting their potential for BNCT and warranting further research. ■ INTRODUCTION Boron neutron capture therapy (BNCT) is a promising cancer treatment modality, particularly effective against radioresistant and highly invasive tumors. 1 This method exploits the unique capability of nonradioactive boron-10 (10B) to capture thermal neutrons, leading to a nuclear fission reaction. This reaction generates two high-energy particles: an α particle with an energy of approximately 150 keV μm−1 and 7Li nuclei with an energy of around 175 keV μm−1 .2 These particles are characterized by high linear energy transfer (LET) and limited path lengths between 4 to 9 μm, effectively confining their ionization energy within the diameter of a single cell.3 As a result, BNCT facilitates the targeted destruction of cancer cells enriched with 10B, while sparing the surrounding healthy tissues. The success of BNCT critically depends on the tumorspecific uptake of boron-10 agents. Therefore, the development of selective boron delivery agents is of the utmost importance. According to the established criteria for an ideal BNCT agent,4 the optimal boron concentration in tumor tissues should range between 20 and 35 μg of 10B per gram of tumor tissue, which equates to approximately 109 boron-10 atoms per cell. Additionally, an essential criterion for these agents is achieving a tumor-to-normal tissue ratio exceeding 3:1. This ratio is crucial to ensure targeted destruction of tumor cells, while minimizing damage to adjacent healthy cells. In light of these requirements, contemporary research efforts have been intensively focused on developing boron-10 agents with enhanced tumor-specific accumulation capabilities. To date, the U.S. Food and Drug Administration has approved only two boron compounds for BNCT clinical trials: sodium borocaptate (BSH) and L-4-dihydroxyboronylphenylalanine (BPA) that are approved by the U.S. Food and Drug Administration for clinical trials.5,6 BPA is a derivative of the amino acid phenylalanine, exhibiting selective tumor cell uptake due to the overexpression of the L-amino acid transporters (LAT1) across various cancer types.7 This feature endows BPA with a higher selectivity for uptake by tumor cells. Conversely, BSH, a member of the polyhedral boranes, boasts a significantly higher boron content compared to BPA, with ap

FAQs

What is the key role of boron-10 in boron neutron capture therapy (BNCT)?

BNCT relies on boron-10 capturing thermal neutrons, which triggers nuclear fission and produces high-energy particles. Those particles destroy cancer cells enriched with boron-10 while sparing surrounding healthy tissue.

How were the boronate ester polymer micelles prepared for BNCT application?

The boron-rich micelles were synthesized via atom transfer radical polymerization from poly(ethylene glycol)-block-(poly(4-vinylphenyl boronate ester)).

What evidence supports that the micelles enhance tumor boron delivery and therapeutic effect?

Transmission electron microscopy shows uniform micelle size, and sonication helps preserve morphology after lyophilization and reconstitution. In vitro studies show a large increase in boron accumulation versus BPA, and in vivo tumor-bearing mice show improved tumor-to-blood selectivity and delayed tumor growth.

Sep 22, 2026

Upload by Liam