TY - JOUR
T1 - Dynamics of different-sized solid-state nanocrystals as tracers for a drug-delivery system in the interstitium of a human tumor xenograft
AU - Kawai, Masaaki
AU - Higuchi, Hideo
AU - Takeda, Motohiro
AU - Kobayashi, Yoshio
AU - Ohuchi, Noriaki
N1 - Funding Information:
Noriaki Ohuchi has received research grants from Takeda Pharmaceutical Company Limited, and Konica Minolta Medical & Graphic, Inc. Motohiro Takeda has received a research grant from Konica Minolta Medical & Graphic, Inc. Masaaki Kawai, Hideo Higuchi, and Yoshio Kobayashi have no competing interests.
Funding Information:
This work was supported by Grants-in-Aid for the Research Project, Promotion of Advanced Medical Technology (H14-Nano-010) and Grants-in-Aid for the Research Project, Promotion of Medical Instruments, from the Ministry of Health, Labor and Welfare of Japan (H18-Nano-001; NO), Grant-in-Aid for Scientific Research (B) (20310067;NO) and Grant-in-Aid for Young Scientists (Start-up) (20890018;MK) from Japan Society for the Promotion of Science (JSPS), Core Research for Evolutional Science and Technology (CREST) from the Japan Science and Technology Agency (JST; HH) and Special Coordination Funds for Promoting Science and Technology of Japan (HH). We express our thanks to Prof. N. Suzuki and Dr. M. Sato from the Department of Advanced Interdisciplinary Sciences, Graduate School of Engineering, Utsunomiya University, Japan, for assistance in measuring the zeta potential of particles and for fruitful discussions.
PY - 2009/7/3
Y1 - 2009/7/3
N2 - Introduction: Recent anticancer drugs have been made larger to pass selectively through tumor vessels and stay in the interstitium. Understanding drug movement in association with its size at the single-molecule level and estimating the time needed to reach the targeted organ is indispensable for optimizing drug delivery because single cell-targeted therapy is the ongoing paradigm. This report describes the tracking of single solid nanoparticles in tumor xenografts and the estimation of arrival time.Methods: Different-sized nanoparticles measuring 20, 40, and 100 nm were injected into the tail vein of the female Balb/c nu/nu mice bearing human breast cancer on their backs. The movements of the nanoparticles were visualized through the dorsal skin-fold chamber with the high-speed confocal microscopy that we manufactured.Results: An analysis of the particle trajectories revealed diffusion to be inversely related to the particle size and position in the tumor, whereas the velocity of the directed movement was related to the position. The difference in the velocity was the greatest for 40-nm particles in the perivascular to the intercellular region: difference = 5.8 nm/s. The arrival time of individual nanoparticles at tumor cells was simulated. The estimated times for the 20-, 40-, and 100-nm particles to reach the tumor cells were 158.0, 218.5, and 389.4 minutes, respectively, after extravasation.Conclusions: This result suggests that the particle size can be individually designed for each goal. These data and methods are also important for understanding drug pharmacokinetics. Although this method may be subject to interference by surface molecules attached on the particles, it has the potential to elucidate the pharmacokinetics involved in constructing novel drug-delivery systems involving cell-targeted therapy.
AB - Introduction: Recent anticancer drugs have been made larger to pass selectively through tumor vessels and stay in the interstitium. Understanding drug movement in association with its size at the single-molecule level and estimating the time needed to reach the targeted organ is indispensable for optimizing drug delivery because single cell-targeted therapy is the ongoing paradigm. This report describes the tracking of single solid nanoparticles in tumor xenografts and the estimation of arrival time.Methods: Different-sized nanoparticles measuring 20, 40, and 100 nm were injected into the tail vein of the female Balb/c nu/nu mice bearing human breast cancer on their backs. The movements of the nanoparticles were visualized through the dorsal skin-fold chamber with the high-speed confocal microscopy that we manufactured.Results: An analysis of the particle trajectories revealed diffusion to be inversely related to the particle size and position in the tumor, whereas the velocity of the directed movement was related to the position. The difference in the velocity was the greatest for 40-nm particles in the perivascular to the intercellular region: difference = 5.8 nm/s. The arrival time of individual nanoparticles at tumor cells was simulated. The estimated times for the 20-, 40-, and 100-nm particles to reach the tumor cells were 158.0, 218.5, and 389.4 minutes, respectively, after extravasation.Conclusions: This result suggests that the particle size can be individually designed for each goal. These data and methods are also important for understanding drug pharmacokinetics. Although this method may be subject to interference by surface molecules attached on the particles, it has the potential to elucidate the pharmacokinetics involved in constructing novel drug-delivery systems involving cell-targeted therapy.
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U2 - 10.1186/bcr2330
DO - 10.1186/bcr2330
M3 - Article
C2 - 19575785
AN - SCOPUS:77449084996
VL - 11
JO - Breast Cancer Research
JF - Breast Cancer Research
SN - 1465-5411
IS - 4
M1 - R43
ER -