Polymer-Coated Nanoparticles for Therapeutic and Diagnostic Non-10B Enriched Polymer-Coated Boron Carbon Oxynitride (BCNO) Nanoparticles as Potent BNCT Drug.

Chen-Wei Chiang,Yun-Chen Chien,Pei-Yuin Keng,Wen-Jui Yu,Tzu-Wei Wang,Chia-Yu Ho,Chi-Shiun Chiang,Chih-Yi Wang

doi:10.3390/nano11112936

Chen-Wei Chiang, Yun-Chen Chien + Show 6 more

Open Access

https://doi.org/10.3390/nano11112936

Copy DOI

Abstract

Boron neutron capture therapy (BNCT) is a powerful and selective anti-cancer therapy utilizing 10B-enriched boron drugs. However, clinical advancement of BCNT is hampered by the insufficient loading of B-10 drugs throughout the solid tumor. Furthermore, the preparation of boron drugs for BNCT relies on the use of the costly B-10 enriched precursor. To overcome these challenges, polymer-coated boron carbon oxynitride (BCNO) nanoparticles, with ~30% of boron, were developed with enhanced biocompatibility, cell uptake, and tumoricidal effect via BNCT. Using the ALTS1C1 cancer cell line, the IC50 of the PEG@BCNO, bare, PEI@BCNO were determined to be 0.3 mg/mL, 0.1 mg/mL, and 0.05 mg/mL, respectively. As a proof-of-concept, the engineered non-10B enriched polymer-coated BCNO exhibited excellent anti-tumor effect via BNCT due to their high boron content per nanoparticle and due to the enhanced cellular internalization and retention compared to small molecular 10B-BPA drug. The astrocytoma ALTS1C1 cells treated with bare, polyethyleneimine-, and polyethylene glycol-coated BCNO exhibited an acute cell death of 24, 37, and 43%, respectively, upon 30 min of neutron irradiation compared to the negligible cell death in PBS-treated and non-irradiated cells. The radical approach proposed in this study addresses the expensive and complex issues of B-10 isotope enrichment process; thus, enabling the preparation of boron drugs at a significantly lower cost, which will facilitate the development of boron drugs for BNCT.

Highlights

This treatment paradigm can lead to significant toxicity and side effects in patients because both treatments destroy the neighboring healthy tissues surrounding the cancer cells or healthy tissues that are in the lane of the radiation beam
Boron neutron capture therapy (BNCT) is an alternative radiotherapy that enables the selective destruction of individual cancer cells when a boron drug is administered
TEM images in Figure 1 revealed the as prepared boron carbon oxynitride (BCNO) nanoparticles is irregular in shapes with an average lateral diameter of 6.1 ± 0.73 nm) and possessed a turbostractic boron nitride diffraction patterns. (Figure 1a and Figure S1—XRD) The as prepared bare BCNO quasi-spherical nanoparticles and the PEG@BCNO nanoparticles remained dispersed in aqueous solution and randomly assembled onto the TEM Cu grid as shown in

Summary

Introduction

More than 50% of cancer patients received radiation therapy during their course of treatment [1]. The combination of chemotherapy and radiation therapy remains the first line of treatment in the clinical management of several solid tumors. This treatment paradigm can lead to significant toxicity and side effects in patients because both treatments (i.e., chemotherapy and radiation therapy) destroy the neighboring healthy tissues surrounding the cancer cells or healthy tissues that are in the lane of the radiation beam. Boron neutron capture therapy (BNCT) is an alternative radiotherapy that enables the selective destruction of individual cancer cells when a boron drug is administered

Methods

Results

Conclusion