The potential of liposomes with carbonic anhydrase IX to deliver anticancer ingredients to cancer cells in vivo

Abstract

Drug delivery nanocarriers, especially targeted drug delivery by liposomes are emerging as a class of therapeutics for cancer. Early research results suggest that liposomal therapeutics enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumors and active cellular uptake. Here, we highlight the features of immunoliposomes that distinguish them from previous anticancer therapies, and describe how these features provide the potential for therapeutic effects that are not achievable with other modalities. While a large number of studies has been published, the emphasis here is placed on the carbonic anhydrase IX (CA-IX) and the conjugated liposomes that are likely to open a new chapter on drug delivery system by using immunoliposomes to deliver anticancer ingredients to cancer cells in vivo.

Figure 1

Dimeric structure of CA-ΙΧ. SP, signal peptide; PG, proteoglycan-like segment; CA, carbonic anhydrase domain; TM, transmembrane anchor; IC, intracytoplasmic tail [92].

Figure 2

Introduction of sulfhydryl group in IgG antibodies (such as G250 mAb) via enzymatic digestion. Enzyme digestion of IgG antibodies with papain results in cleavage of the hinge region above the interchain disulfides. This produces two identical Fab fragments (heavy-light chain pairs), each containing one antigen binding site and one Fc region. Pepsin digestion of IgG antibodies cleaves below the disulphides in the hinge region, resulted in the formation of a bivalent fragment F(ab)₂. The remaining Fc region is extensively degraded into smaller peptide fragments. F(ab)₂ fragments are subsequently reduced with MEA-HCl and produced two Fab fragments.