The anticancer efficacy of pixantrone-loaded liposomes decorated with sialic acid-octadecylamine conjugate.
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.
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Zhennan
Z
She
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Ting
T
Zhang
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Xuling
X
Wang
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Xuan
X
Li
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Yanzhi
Y
Song
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Xiaobo
X
Cheng
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Zhenjun
Z
Huang
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China. Electronic address: pharmdeng@gmail.com.
Yihui
Y
Deng
D000588:Amines / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D007546:Isoquinolines / Q000737:chemistry* / Q000627:therapeutic use*; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D023041:Xenograft Model Antitumor Assays
D000588:Amines; D000970:Antineoplastic Agents; D007546:Isoquinolines; D008081:Liposomes; C086548:pixantrone; C009317:stearylamine; D019158:N-Acetylneuraminic Acid
Liposome pixantrone; Sialic acid–octadecylamine conjugate; Tumor shed; Tumor-associated macrophages