Targeted delivery of epirubicin to tumor-associated macrophages by sialic acid-cholesterol conjugate modified liposomes with improved antitumor activity.
With the knowledge that the receptors of sialic acid are overexpressed on the surface of tumor-associated macrophages (TAMs), which play a crucial role in the tumor's progression and metastasis, a sialic acid-cholesterol conjugate (SA-CH) was synthesized and modified on the surface of epirubicin (EPI)-loaded liposomes (EPI-SAL) to improve the delivery of EPI to the TAMs. The liposomes were developed using remote loading technology via a pH gradient. The liposomes were evaluated for particle size, encapsulation efficiency, in vitro release, stability, in vitro cytotoxicity and pharmacokinetics. And the in vitro and in vivo cellular uptake studies demonstrated EPI-SAL achieved enhanced accumulation of EPI into TAMs. The antitumor studies indicated that EPI-SAL provided the strongest antitumor activity compared with the other formulations (EPI-S, EPI-CL and EPI-PL represent EPI solution, conventional liposomal EPI, PEGylated liposomal EPI, respectively), and the survival percent of tumor-bearing mice was 83.3%. The superior antitumor efficacy was probably attributed to the killing of TAMs by EPI-SAL, and modulating the tumor microenvironment with the depletion of TAMs. These findings suggested that SA-CH decorated EPI-loaded liposomes may present an effective strategy to eradicate TAMs, which may be a promising approach for cancer therapy.
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China.
Songlei
S
Zhou
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China.
Ting
T
Zhang
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China.
Bo
B
Peng
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China.
Xiang
X
Luo
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China.
Xinrong
X
Liu
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China.
Ling
L
Hu
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China.
Yang
Y
Liu
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China.
Donghua
D
Di
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China.
Yanzhi
Y
Song
College of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, PR China, PR China. Electronic address: pharmdeng@gmail.com.
Yihui
Y
Deng
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry*; D065546:Drug Liberation; D004355:Drug Stability; D015251:Epirubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000067996:RAW 264.7 Cells; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D015251:Epirubicin; D002784:Cholesterol; D019158:N-Acetylneuraminic Acid
Antitumor activity; Epirubicin; Liposomes; Sialic acid; Tumor-associated macrophages