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

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.

Recent progress of nano-drugs in neutron capture therapy

“…Lan et al prepared a polyethylene-glycol-coated boron carbon oxynitride nanoparticle (PEG@BCNO), it showed better therapeutic performance in animal models than that of 10 BPA 66 . Besides PEG@BCNO, Chiang et al coated BCNO with polyethyleneimine (PEI), the PEI@BCNO exhibited higher boron content of 48μg B/g of tumor cell, while PEG@BCNO only reached 16μg 10 B/g of tumor cell in in-vitro studies (Figure 7 D) 67 . However, these nanoparticles lack targeting ability towards tumor cells, so further surface modification with antibody or specific proteins might largely improve the tumor cell uptake of 10 B, which leads to better clinical effects.…”

“…(D) Schematic illustration of functionalization of BCNO nanoparticles with PEI and PEG. Reproduced with permission from 67 . Copyright 2021, MDPI (Basel, Switzerland).…”

Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers

“…For effective BNCT, most of the current delivery strategies rely on 10 B-enriched boron precursors to achieve therapeutic boron levels in the tumor cells. To avoid the high costs associated with the 10 B enrichment process, Chiang et al prepared non- 10 B-enriched polymer-coated boron carbon oxynitride (BCNO) NPs to conduct a BNCT theranostic study [ 118 ]. BNCO is a non-toxic earth phosphor that requires no additional labeling modifications for its applications, due to its photoluminescence property.…”

Boron Vehiculating Nanosystems for Neutron Capture Therapy in Cancer Treatment

“…Considering the high time and cost consumption of the 10 B-enrichment process, limiting the clinical advances of BNCT agents, some research groups focused on the development of boron NPs whose efficacy only depends on the 10 B natural abundance. In this context, Chiang et al [ 116 ] developed polymer-coated boron carbon oxynitride (BCNO) NPs, possessing inherent luminescence, as a potential theranostic agent for BNCT. The NPs, prepared by a low-temperature sintering process using boric acid as a boron source, were coated with PEI or PEG.…”