Nanoprobes for two-photon excitation time-resolved imaging of living animals: In situ analysis of tumor-targeting dynamics of nanocarriers.
Great challenges remain in the noninvasive luminescence imaging analysis of tumor-targeting dynamics of nanocarriers in living animals which is of significance for the development of anti-cancer nanomedicine. In this work, luminescent nanoparticles Eu(tta)3bpt@SMA (dav = 15 nm), which exhibited good water dispersion stability and high yields of red Eu-luminescence under near-infrared two-photon excitation, were prepared by a modified microfluidic mixing method in the absence of surfactants. Tumor-targeting agents, Arg-Gly-Asp-D-Phe-Lys (cRGD) polypeptide or transferrin (Tf), were then anchored on the nanoparticle surfaces to form the desired nanocarriers Eu@SMA-RGD or Eu@SMA-Tf. The tumor-targeting processes of the prepared nanocarriers in intact living mice were analyzed on a home-built two-photon excitation time-resolved (TPE-TR) imaging apparatus having a wide view filed. The TPE-TR strategy could effectively suppress the interference from biological autofluorescence, which allowed the targeted domains to be visualized with a high signal-to-noise ratio. It was found that the tumor-tissue trapping efficacy of Eu@SMA-RGD was much higher than that of Eu@SMA-Tf, and the desorption process from the tumor tissues of Eu@SMA-RGD was slower than that of Eu@SMA-Tf. The methods developed in this work pave a way to investigate the in vivo tumor-targeting dynamics of nanocarriers by noninvasive luminescence imaging of living animals.
Beijing National Laboratory for Molecular Science, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Wen
W
Yang
Department of Chemistry, Renmin University of China, Beijing, 100872, China.
Li-Min
LM
Fu
Beijing National Laboratory for Molecular Science, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Xue
X
Wen
Beijing National Laboratory for Molecular Science, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Ying
Y
Liu
Department of Biophysics, School of Basic Medical Sciences and Biomed-X Center, Peking University, Beijing, 100191, China.
Ye
Y
Tian
Department of Chemistry, Renmin University of China, Beijing, 100872, China.
Yu-Chen
YC
Liu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.
Rong-Cheng
RC
Han
Beijing National Laboratory for Molecular Science, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Zhi-Yue
ZY
Gao
Beijing National Laboratory for Molecular Science, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Tian-En
TE
Wang
Department of Biophysics, School of Basic Medical Sciences and Biomed-X Center, Peking University, Beijing, 100191, China.
Yin-Lin
YL
Sha
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.
Yu-Qiang
YQ
Jiang
Beijing National Laboratory for Molecular Science, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. Electronic address: wangy@pku.edu.cn.
Yuan
Y
Wang
Department of Chemistry, Renmin University of China, Beijing, 100872, China. Electronic address: jpzhang@chem.ruc.edu.cn.
Jian-Ping
JP
Zhang
D000818:Animals; D005063:Europium / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging*; D049408:Luminescent Agents / Q000737:chemistry*; D008163:Luminescent Measurements / Q000379:methods*; D008298:Maleates / Q000737:chemistry*; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D061848:Optical Imaging / Q000379:methods*; D010456:Peptides, Cyclic / Q000737:chemistry; D017785:Photons; D011137:Polystyrenes / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry
D049408:Luminescent Agents; D008298:Maleates; D010456:Peptides, Cyclic; D011137:Polystyrenes; D014168:Transferrin; C507169:cyclic arginine-glycine-aspartic acid peptide; C024074:styrene-maleic acid polymer; D005063:Europium
Nanocarriers; Nanoprobes; Noninvasive luminescence analysis; Time-resolved imaging; Tumor-targeting dynamics; Two-photon-excitation