Preparation and In Vitro Evaluation of a MRI Contrast Agent Based on Aptamer-Modified Gadolinium-Loaded Liposomes for Tumor Targeting.
The aim of this study was to prepare aptamer-modified liposomes loaded with gadolinium (Gd) to enhance the effective diagnosis for tumor by MRI. A modified GBI-10 (GBI-10m) was used to prepare targeted liposomes (GmLs). Liposomes with GBI-10 aptamer (GLs) and without aptamer (non-targeted liposomes (NLs)) were also prepared as controls. The particle size and zeta potential of GmLs, GLs, and NLs were all assayed. A clinical 3.0 T MR scanner was employed to assess the imaging efficiency and measure the longitudinal relaxivity (r1) of the above liposomes. Confocal laser scanning microscopy and flow cytometry were used to analyze and compare the targeting effects of GmLs, GLs, and NLs to MDA-MB-435s cells at 37°C. The particle size of the prepared liposomes was scattered at 100-200 nm, and their values of r1were ∼4 mM-1s-1. The images of confocal laser scanning microscopy showed that GmLs in the cytoplasm were significantly more than GLs and both GmLs and GLs were more than NLs. The fluorescence intensity of GmLs was increased by about two times than that of GLs and three times than that of NLs by flow cytometry. Therefore, the GmLs in this initial study were suggested to be a potential MRI contrast agent at 37°C for diagnosing tumors with the protein of tenascin-C over-expressed.
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.|Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
Lan-Xin
LX
Zhang
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
Kun-Feng
KF
Li
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.|Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
Huan
H
Wang
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.|Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
Meng-Jie
MJ
Gu
Department of Radiology, Peking University Third Hospital, Beijing, 100191, China.
Li-Si
LS
Liu
Department of Radiology, Peking University Third Hospital, Beijing, 100191, China.
Zhuo-Zhao
ZZ
Zheng
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
Nan-Yin
NY
Han
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China. yangzj@bjmu.edu.cn.
Zhen-Jun
ZJ
Yang
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China. tianyuan_fan@bjmu.edu.cn.|Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. tianyuan_fan@bjmu.edu.cn.
Tian-Yuan
TY
Fan
D000818:Animals; D052157:Aptamers, Nucleotide / Q000494:pharmacology; D003287:Contrast Media / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D005682:Gadolinium / Q000494:pharmacology*; D006801:Humans; D008081:Liposomes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D018613:Microscopy, Confocal / Q000379:methods; D009369:Neoplasms / Q000175:diagnosis*; D010316:Particle Size
D052157:Aptamers, Nucleotide; D003287:Contrast Media; D008081:Liposomes; D005682:Gadolinium
aptamer; contrast agent; liposomes; magnetic resonance imaging; target