Aydemir, U., Ugur, E., Ermis, C., Aydemir, F. N., Ozdemir, E., Banerjee, S., et al. (2022). Boron Cage Triggered Micellization of a Neutral–Cationic Block Copolymer and Preparation of Boron-Containing Layer-by-Layer Microparticles. ACS Applied Polymer Materials, 4(5), 3448-3461. DOI: 10.1021/acsapm.2c00060

The preparation of a polymer carrier for a boron delivery agent is presented through a combination of experimental and computational studies. A dodecahydro-closo-dodecaborate (B₁₂H₁₂)^2– (B₁₂) anion was used as a model boron-containing agent due to its high boron content. Quaternized poly(2-vinyl pyridine)-b-poly(ethylene oxide) (QP₂VP-b-PEO) was chosen as a model neutral–cationic block copolymer to construct the carrier. The electrostatic association between QP₂VP and B₁₂ induced the self-assembly of QP₂VP-b-PEO, resulting in micelles with (B₁₂ + QP₂VP)-core and PEO-corona. The mechanism of formation of (B12 + QP2VP)-b-PEO micelles was examined through density functional theory (DFT) calculations and classical simulations. (B12 + QP2VP)-b-PEO micelles were found to be undurable in biological medium. To enhance stability, micelles were utilized as building blocks together with poly(N-vinyl caprolactam) (PVCL) and tannic acid (TA) to construct layer-by-layer (LbL) microparticles. Cytotoxicity and cellular association of LbL particles were assessed using the HepG₂ cell line. Multilayered particles were found to show no cellular cytotoxicity. Association studies and the boron content of treated cells through inductively coupled plasma optical emission spectroscopy (ICP-OES) showed that LbL microparticles were extensively associated with and successfully delivered boron to HepG₂ cells. This study reveals the challenges and possible solutions to obtain stable self-assembled structures in a cell culture medium. These findings contribute to a fundamental understanding of the structure–property relationship in self-assembled micelles/LbL particles and provide a basis for further development of boron-containing polymer vehicles for boron neutron capture therapy.