The anti-glypican 1 AT101 antibody as targeting agent to effectively deliver chitosan nanobubbles to glioblastoma cells

Abstract

Background: Recently, we developed AT101, an IgM-class mouse monoclonal antibody directed against glypican-1 (GPC1), a proteoglycan that can be considered as useful target for glioblastoma multiforme (GBM) treatment being specifically and highly expressed on GBM cell surface. Here, we proposed the use of AT101 as targeting agent in a drug delivery nanoplatfom to effectively deliver chitosan nanobubbles (NBs) for GBM treatment.

Methods: Chitosan NBs were prepared and conjugated with AT101 or left unconjugated as control.

Results: The ability of AT101 to bind the GPC1 protein was demonstrated by flow cytometry and immunofluorescence analysis in the "GBM-like" GPC1-expressing cell lines U-87 MG and T98G. AT101 was shown to bind GPC1-expressing GBM tumor samples by immunofluorescence. In-vivo experiments in the U-87 MG xenograft model showed that AT101 was able to bind GPC1 on cell surface and accumulate in U-87 MG tumor masses (p = 0.0002 respect to control). Moreover, in-vivo experiments showed that AT101 is able to target GPC1 when conjugated to chitosan NBs, thus increasing their specific deliver to GPC1-expressing cells of U-87 MG tumor, as compared to chitosan NBs not conjugated to AT101 (p = 0.02).

Conclusions: AT101 is an useful targeting agent for the development of drug delivery nanoplatforms for GBM treatment.

Keywords: GBM; GPC1; chitosan nanobubbles; monoclonal antibody; targeted therapy.