Polymer-Directed Self-Assembly of BCNO Nanoparticles for Efficient Boron Utilization in Boron Neutron Capture Therapy.
5 affiliations
- 1Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu City 300, Taiwan.
- 2Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu City 300, Taiwan.
- 3Boron Neutron Capture Therapy (BNCT) center, National Tsing Hua University, Hsinchu City 300, Taiwan.
- 4Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu City 300, Taiwan.
- 5Institute of Oral Biology, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Abstract
Boron carbon oxynitride (BCNO) nanoparticles are attractive boron-rich agents for boron neutron capture therapy (BNCT), yet their polymer-directed self-assembly, structural regulation, and delivery-function relationships remain insufficiently explored. Here, we report a stimuli-responsive polymer-BCNO nanoassembly, mPEG/PS-b-PEI@BCNO, that integrates macromolecular self-assembly with efficient boron utilization for BNCT against pancreatic cancer. The amphiphilic mPEG/PS-b-PEI copolymer was constructed by coupling methoxy poly-(ethylene glycol) (mPEG), polystyrene (PS), and poly-(ethylenimine) (PEI) through acid-labile Schiff-base linkages. Electrostatic complexation between negatively charged BCNO nanoparticles and cationic PEI, combined with solvent-driven amphiphilic assembly, generated spherical nanoassemblies with tunable morphology, size, and surface charge. Systematic variation of the mPEG/PS ratio revealed that the hydrophobic-hydrophilic balance of the copolymer governs BCNO packing and nanoassembly formation. The optimized mPEG/PS-b-PEI@BCNO nanoassemblies exhibited a uniform diameter of approximately 61 nm, positive surface charge, PEG-mediated colloidal stabilization, and acid-triggered disassembly into smaller BCNO-containing fragments under tumor-relevant acidic conditions. Despite a relatively low BCNO content of approximately 8 wt %, mPEG/PS-b-PEI@BCNO markedly improved boron delivery in UN-KC-6141 pancreatic cancer cells; the nanoassemblies achieved higher boron uptake efficiency than bare BCNO and boronophenylalanine (BPA). In 3D pancreatic tumor spheroids, mPEG/PS-b-PEI@BCNO delivered boron concentrations above the therapeutic threshold for BNCT and exhibited boron utilization efficiencies of 16.64% at pH 7.4 and 10.89% at pH 6.5. Under equivalent ¹⁰B dosing, the nanoassemblies produced the strongest BNCT response in 3D spheroids, inducing approximately 52% cell death and significantly outperforming bare BCNO and BPA. These findings demonstrate that polymer-controlled nanoassembly architecture enhances boron utilization without relying solely on high intrinsic boron loading, establishing a design framework for the next-generation BNCT nanodrugs.
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BibTeX
@article{chan2026polymerdirected,
title = {{Polymer-Directed Self-Assembly of BCNO Nanoparticles for Efficient Boron Utilization in Boron Neutron Capture Therapy.}},
author = {Wei-Hsin Chan and Lu-Ang Chen and Wei-Yuan Huang and Lin-Sheng Yu and Tzu-Chieh Sun and Fang-Hsin Chen and Chi-Shuo Chen and Tzu-Wei Wang and Pei-Yuin Keng},
journal = {ACS nanoscience Au},
year = {2026},
month = sep,
doi = {10.1021/acsnanoscienceau.6c00088},
url = {https://europepmc.org/article/MED/42921422},
note = {CC BY},
}
RIS
TY - JOUR
TI - Polymer-Directed Self-Assembly of BCNO Nanoparticles for Efficient Boron Utilization in Boron Neutron Capture Therapy.
AU - Wei-Hsin Chan
AU - Lu-Ang Chen
AU - Wei-Yuan Huang
AU - Lin-Sheng Yu
AU - Tzu-Chieh Sun
AU - Fang-Hsin Chen
AU - Chi-Shuo Chen
AU - Tzu-Wei Wang
AU - Pei-Yuin Keng
PY - 2026
DA - 2026/09/26
JO - ACS nanoscience Au
DO - 10.1021/acsnanoscienceau.6c00088
UR - https://europepmc.org/article/MED/42921422
AB - Boron carbon oxynitride (BCNO) nanoparticles are attractive boron-rich agents for boron neutron capture therapy (BNCT), yet their polymer-directed self-assembly, structural regulation, and delivery-function relationships remain insufficiently explored. Here, we report a stimuli-responsive polymer-BCNO nanoassembly, mPEG/PS-b-PEI@BCNO, that integrates macromolecular self-assembly with efficient boron utilization for BNCT against pancreatic cancer. The amphiphilic mPEG/PS-b-PEI copolymer was constructed by coupling methoxy poly-(ethylene glycol) (mPEG), polystyrene (PS), and poly-(ethylenimine) (PEI) through acid-labile Schiff-base linkages. Electrostatic complexation between negatively charged BCNO nanoparticles and cationic PEI, combined with solvent-driven amphiphilic assembly, generated spherical nanoassemblies with tunable morphology, size, and surface charge. Systematic variation of the mPEG/PS ratio revealed that the hydrophobic-hydrophilic balance of the copolymer governs BCNO packing and nanoassembly formation. The optimized mPEG/PS-b-PEI@BCNO nanoassemblies exhibited a uniform diameter of approximately 61 nm, positive surface charge, PEG-mediated colloidal stabilization, and acid-triggered disassembly into smaller BCNO-containing fragments under tumor-relevant acidic conditions. Despite a relatively low BCNO content of approximately 8 wt %, mPEG/PS-b-PEI@BCNO markedly improved boron delivery in UN-KC-6141 pancreatic cancer cells; the nanoassemblies achieved higher boron uptake efficiency than bare BCNO and boronophenylalanine (BPA). In 3D pancreatic tumor spheroids, mPEG/PS-b-PEI@BCNO delivered boron concentrations above the therapeutic threshold for BNCT and exhibited boron utilization efficiencies of 16.64% at pH 7.4 and 10.89% at pH 6.5. Under equivalent ¹⁰B dosing, the nanoassemblies produced the strongest BNCT response in 3D spheroids, inducing approximately 52% cell death and significantly outperforming bare BCNO and BPA. These findings demonstrate that polymer-controlled nanoassembly architecture enhances boron utilization without relying solely on high intrinsic boron loading, establishing a design framework for the next-generation BNCT nanodrugs.
SN - 2694-2496
ER -