Phenylboronic-acid-based nanocomplex as a feasible delivery platform of immune checkpoint inhibitor for potent cancer immunotherapy.

Affiliation

Lim J(1), Lee J(2), Jung S(3), Kim WJ(4).
Author information:
(1)Department of Chemistry, POSTECH-CATHOLIC Biomedical Engineering Institute, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
(2)Department of Chemistry, POSTECH-CATHOLIC Biomedical Engineering Institute, Pohang University of Science and Technology, Pohang 37673, Republic of Korea; OmniaMed Co, Ltd., Pohang 37673, Republic of Korea.
(3)School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
(4)Department of Chemistry, POSTECH-CATHOLIC Biomedical Engineering Institute, Pohang University of Science and Technology, Pohang 37673, Republic of Korea; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 37673, Republic of Korea; OmniaMed Co, Ltd., Pohang 37673, Republic of Korea. Electronic address: [Email]

Abstract

Inspired by our previous study, we report a simple yet effective platform for therapeutic antibody delivery. A polymeric phenylboronic acid (pPBA)-antibody nanocomplex was simply formulated by mixing pPBA and antibody, derived by the formation of a pH-responsive phenylboronic ester between the PBA group on pPBA and diol on the inherent glycosylation site of the antibody. We focused on the basic prerequisites for a successful delivery, protection from degradation during the circulation, and release at the target lesion. To evaluate the antibody delivery system, anti-PD-L1, one of the most common antibody therapeutics in immuno-oncology, and mouse colon cancer model with an MC-38 cell line were used. Several in-vitro assays reveal the outstanding protective effect of the nanocomplexes as well as the pH-responsive release of antibodies. Moreover, the anti-PD-L1 nanocomplex exhibited an enhanced circulation as well as a better accumulation in tumor lesions after administration in vivo, which led to a significant antitumor effect in comparison to that of a free antibody. Our nanocomplex platform is a promising antibody delivery system for application in conventional antibody-mediated therapies.