TY - JOUR
T1 - Significant effect of size on the in vivo biodistribution of gold composite nanodevices in mouse tumor models
AU - Balogh, Lajos
AU - Nigavekar, Shraddha S.
AU - Nair, Bindu M.
AU - Lesniak, Wojciech
AU - Zhang, Chunxin
AU - Sung, Lok Yun
AU - Kariapper, Muhammed S.T.
AU - El-Jawahri, Areej
AU - Llanes, Mikel
AU - Bolton, Brian
AU - Mamou, Fatema
AU - Tan, Wei
AU - Hutson, Alan
AU - Minc, Leah
AU - Khan, Mohamed K.
N1 - Funding Information:
This research was federally funded, in part by the U.S. Department of Energy (grant FG01-00NE22943), the Department of Defense (grant DAMD17-03-1-0018), and the National Institutes of Health/National Cancer Institute (grant R01-CA-104479-01). The authors also want to thank Christopher Becker for his valuable contribution to this work.
PY - 2007/12
Y1 - 2007/12
N2 - There is growing interest in developing tissue-specific multifunctional drug delivery systems with the ability to diagnose or treat several diseases. One class of such agents, composite nanodevices (CNDs), is multifunctional nanomaterials with several potential medical uses, including cancer imaging and therapy. Nanosized metal-dendrimer CNDs consist of poly(amidoamine) dendrimers (in various sizes, surface substituents, and net charges) and inorganic nanoparticles, properties of both of which can be individually modified and optimized. In this study we examine effects of size and surface charge on the behavior of Au-dendrimer CNDs in mouse tumor models. Quantitative biodistribution and excretion analyses including 5-nm and 22-nm positive surface, 5-nm and 11-nm negative surface, and a 5-nm neutral surface CNDs were carried out in the B16 mouse melanoma tumor model system. Results seen with the 22-nm CND in the B16 melanoma model were corroborated in a prostate cancer mouse tumor model system. Quantitative in vivo studies confirm the importance of charge and show for the first time the importance of size in affecting CND biodistribution and excretion. Interestingly, CNDs of different size and/or surface charge had high levels of uptake ("selective targeting") to certain organs without specific targeting moieties placed on their surfaces. We conclude that size and charge greatly affect biodistribution of CNDs. These findings have significance for the design of all particle-based nanodevices for medical uses. The observed organ selectivity may make these nanodevices exciting for several targeted medical applications.
AB - There is growing interest in developing tissue-specific multifunctional drug delivery systems with the ability to diagnose or treat several diseases. One class of such agents, composite nanodevices (CNDs), is multifunctional nanomaterials with several potential medical uses, including cancer imaging and therapy. Nanosized metal-dendrimer CNDs consist of poly(amidoamine) dendrimers (in various sizes, surface substituents, and net charges) and inorganic nanoparticles, properties of both of which can be individually modified and optimized. In this study we examine effects of size and surface charge on the behavior of Au-dendrimer CNDs in mouse tumor models. Quantitative biodistribution and excretion analyses including 5-nm and 22-nm positive surface, 5-nm and 11-nm negative surface, and a 5-nm neutral surface CNDs were carried out in the B16 mouse melanoma tumor model system. Results seen with the 22-nm CND in the B16 melanoma model were corroborated in a prostate cancer mouse tumor model system. Quantitative in vivo studies confirm the importance of charge and show for the first time the importance of size in affecting CND biodistribution and excretion. Interestingly, CNDs of different size and/or surface charge had high levels of uptake ("selective targeting") to certain organs without specific targeting moieties placed on their surfaces. We conclude that size and charge greatly affect biodistribution of CNDs. These findings have significance for the design of all particle-based nanodevices for medical uses. The observed organ selectivity may make these nanodevices exciting for several targeted medical applications.
KW - Composite nanodevice
KW - Melanoma
KW - Nanocomposite
KW - PAMAM dendrimer
KW - Tumor biodistribution
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U2 - 10.1016/j.nano.2007.09.001
DO - 10.1016/j.nano.2007.09.001
M3 - Article
C2 - 17962085
AN - SCOPUS:36749089482
SN - 1549-9634
VL - 3
SP - 281
EP - 296
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 4
ER -