Development of Irinotecan Liposome Armed with Dual-Target Anti-Epidermal Growth Factor Receptor and Anti-Fibroblast Activation Protein-Specific Antibody for Pancreatic Cancer Treatment

Abstract

Pancreatic cancer is one of the most common causes of death in Taiwan. Previous studies have shown that more than 90% of pancreatic cancer cells presented epidermal growth factor receptor (EGFR) cell marker, and this marker is thought to be important as it is related to activation of cancer cell proliferation, angiogenesis, and cancer progression. Moreover, tumor-associated fibroblasts were involved in tumor proliferation and progression. In this study, we fabricated an anti-EGFR and anti-fibroblast activation protein bispecific antibody-targeted liposomal irinotecan (BS−LipoIRI), which could specifically bind to pancreatic cancer cells and tumor-associated fibroblasts. The drug encapsulation efficiency of BS−LipoIRI was 80.95%, and the drug loading was 8.41%. We proved that both pancreatic cancer cells and fibroblasts could be targeted by BS−LipoIRI, which showed better cellular uptake efficacy compared to LipoIRI. Furthermore, an in vivo mouse tumor test indicated that BS−LipoIRI could inhibit pancreatic cancer growth up to 46.2% compared to phosphate-buffered saline control, suggesting that BS−LipoIRI could be useful in clinical cancer treatment.

Drug Delivery Strategies for the Treatment of Pancreatic Cancer

“…In a recent study conducted by Lin et al, anti-EGFR and anti-FAP bispecific antibody-targeted liposomal irinotecan was developed to target pancreatic cancer cells and tumor fibroblasts [ 100 ]. The formulation elicited improved cellular uptake and anticancer efficacy in a human pancreatic tumor-bearing mouse model compared to untargeted liposomal irinotecan and the results showed that fibroblast activation protein can be targeted for drug delivery.…”

Advances in Pancreatic Cancer Treatment by Nano-Based Drug Delivery Systems

“…Currently, nanoparticles conjugated to antibodies or peptides to deliver the siRNA to target cancer cells have been the goal of many researchers [ 118 ]. The transferrin receptor (TfR), folate receptor, and Arginine-Glycine-Aspartic ligands are several examples of cell surface target receptors used since several studies prove that they are highly expressed in various types of tumors [ 141 , 142 ].…”

“…The results also showed a similar release rate and a better cellular uptake efficacy of BS-LipoIRI when compared to LipoIRI alone. In vivo testing results also concluded that BS-LipoIRI inhibited cancer growth up to 46.2% when contrasting to the controls, showing the great promise of BS-LipoIRI as a possible novel treatment for pancreatic cancer ( Figure 5 ) [ 118 ].…”

“…Cationic lipid polymers can interact with negatively charged siRNA through ionic interactions. Thus, the self-assembled lipoplexes confer protection to the siRNA, preventing it from undergoing enzymatic degradation, increasing its cellular uptake by endocytosis, increasing the release of siRNA from the endosomal/lysosomal compartment, and promoting its accumulation in the cytosol [ 118 ].…”

“… Profile of irinotecan (IRI) in vitro release from LipoIRI and BS-LipoIRI ( a ); in vitro cytotoxicity of LipoIRI and BS-LipoIRI for BxPC3 pancreatic tumor cells ( b ). Adapted from with permission [ 118 ]. …”