Novel Pancreatic Cancer Therapy Targeting Cell Surface Glycans by Liposomes Modified with rBC2LCN Lectin.

Abstract

INTRODUCTION:

Since the outermost layer of cancer cells is covered with various glycans, targeting these groups may serve as an effective strategy in cancer therapy. We previously reported that fucosylated glycans are specifically expressed on pancreatic cancer cells, and that a protein specifically binding to these glycans, namely rBC2LCN lectin, is a potential guiding drug carrier. In the present study, a novel type of glycan-targeting nanoparticle was developed by modifying the surface of doxorubicin-containing liposomes with rBC2LCN lectin. The efficiency and specificity of this formulation, termed Lec-Doxosome, were examined in vitro and in vivo in human pancreatic cancer models.

METHODS:

Lec-Doxosome was prepared by a post-insertion method based on the insertion of rBC2LCN lectin into the liposomal surface via a lipid linker. The in vitro cellular binding, uptake, and cytotoxicity of Lec-Doxosome were compared with the corresponding parameters in the unmodified liposomes by applying to human pancreatic cancer cell line (Capan-1) with affinity for rBC2LCN lectin. For the in vivo assay, Lec-Doxosome was intravenously injected once per week for a total of 3 weeks into mice bearing subcutaneous tumors.

RESULTS:

The in vitro application of Lec-Doxosome resulted in a 1.2- to 1.6-fold higher intracellular doxorubicin accumulation and a 1.5-fold stronger cytotoxicity compared with the respective rates of accumulation and cytotoxicity in the unmodified liposomes. In vivo, Lec-Doxosome reduced the mean tumor weight (368 mg) compared with that in mice treated with unmodified liposomes (456 mg), without causing any additional adverse events.

CONCLUSION:

It was demonstrated from the results obtained herein that rBC2LCN lectin is a potent modifier, as a means for boosting the efficiency of nanoparticles in the targeting of cancer cell surface glycans.

• Authors: Sota Kimura, Tatsuya Oda, Osamu Shimomura, Tsuyoshi Enomoto, Shinji Hashimoto, Yukihito Kuroda, Yang Yu, Ko Kurimori, Tomoaki Furuta, Yoshihiro Miyazaki, Hiroaki Tateno
• Journal: European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes (Eur Surg Res) Vol. 61 Issue 4-5 Pg. 113-122 ( 2020) ISSN: 1421-9921 [Electronic] Switzerland
• PMID: 33503609 (Publication Type: Journal Article)
• Copyright: © 2021 S. Karger AG, Basel.

Chemical References

• Lectins
• Polysaccharides
• liposomal doxorubicin
• Polyethylene Glycols
• Doxorubicin

Topics

• Animals
• Cell Line, Tumor
• Doxorubicin (administration & dosage, analogs & derivatives, chemistry, metabolism)
• Drug Delivery Systems
• Female
• Humans
• Lectins (chemistry, metabolism)
• Mice
• Mice, Inbred BALB C
• Nanoparticles (chemistry)
• Pancreatic Neoplasms (drug therapy)
• Polyethylene Glycols (administration & dosage, chemistry, metabolism)
• Polysaccharides (metabolism)