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

J Control Release. 2021 Feb 10:330:1168-1177. doi: 10.1016/j.jconrel.2020.11.024. Epub 2020 Nov 17.

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.

Keywords: Antitumor therapy; Cancer immunotherapy; Immune checkpoint inhibitor; Nanocomplex; Phenylboronic ester.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Boronic Acids / therapeutic use
  • Cell Line, Tumor
  • Immune Checkpoint Inhibitors*
  • Immunotherapy
  • Mice
  • Neoplasms* / drug therapy

Substances

  • Boronic Acids
  • Immune Checkpoint Inhibitors
  • benzeneboronic acid