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.