Sialic Acid Conjugate-Modified Cationic Liposomal Paclitaxel for Targeted Therapy of Lung Metastasis in Breast Cancer: What a Difference the Cation Content Makes.

Abstract

Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand-receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.

• Authors: Wenliang Sun, Chao Han, Ruirui Ge, Xiaotong Jiang, Yu Wang, Yingchao Han, Ning Wang, Yanzhi Song, Mingshi Yang, Guoliang Chen, Yihui Deng
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 21 Issue 4 Pg. 1625-1638 (Apr 01 2024) ISSN: 1543-8392 [Electronic] United States
• PMID: 38403951 (Publication Type: Journal Article)

Chemical References

• Liposomes
• N-Acetylneuraminic Acid
• COVID-19 Vaccines
• Paclitaxel
• Lipids
• Cations

Topics

• Humans
• Female
• Liposomes (chemistry)
• N-Acetylneuraminic Acid (chemistry)
• Breast Neoplasms (drug therapy)
• COVID-19 Vaccines
• Paclitaxel (therapeutic use)
• Lung Neoplasms (drug therapy)
• Lipids
• Cations
• Cell Line, Tumor