Journal
BIOMATERIALS
Volume 35, Issue 19, Pages 5216-5225Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.03.022
Keywords
Sialic acid-octadecylamine conjugate; Tumor shed; Liposome pixantrone; Tumor-associated macrophages
Funding
- National Natural Science Foundation of China [81373334]
Ask authors/readers for more resources
Based on the knowledge that sialic acid is a critical element for tumor development and its receptors are highly expressed on the tumor-associated macrophages (TAMs) which play important roles in the growth and metastasis of tumors, we synthesized a sialic acid octadecylamine conjugate (SA ODA) and anchored it on the surface of pixantrone (Pix)-loaded liposomes, to achieve an improved anticancer effect. Four Pix formulations (Pix-S, Pix-CL, Pix-PL and Pix-SAL represent solution, conventional liposome, stealth liposome, and SA ODA modified liposome, respectively) were developed, and various parameters, including drug loading, stability, in vitro release, cytotoxicity and pharmacokinetics, were evaluated. The tumor growth inhibition and toxicity studies were performed in S180-bearing Kunming mice. Pix-S exhibited a strong toxicity to the immune system, accelerated the growth of tumors and reduced the lifespan of mice. In contrast, Pix-SAL displayed the strongest anticancer and life-prolonging effects among all of the formulations in this study. More importantly, injection of Pix-SAL induced a phenomenon whereby the cancerous tissues were shed from mice, after which the wound healed. We speculate that this special efficacy may be partly due to the killing of TAMs by Pix-SAL. This study suggests that SA ODA modified liposomes may serve as an effective intravenous delivery vehicle for Pix. (c) 2014 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available