Significant effect of size on the in vivo biodistribution of gold composite nanodevices in mouse tumor models.
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.
Balogh
Lajos
L
The NanoBiotechnology Center at Roswell Park Cancer Institute (NBC at RPCI), Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Nigavekar
Shraddha S
SS
Nair
Bindu M
BM
Lesniak
Wojciech
W
Zhang
Chunxin
C
Sung
Lok Yun
LY
Kariapper
Muhammed S T
MS
El-Jawahri
Areej
A
Llanes
Mikel
M
Bolton
Brian
B
Mamou
Fatema
F
Tan
Wei
W
Hutson
Alan
A
Minc
Leah
L
Khan
Mohamed K
MK
D000818:Animals; D045744:Cell Line, Tumor; D006046:Gold / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure*; D009928:Organ Specificity; D010316:Particle Size; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014018:Tissue Distribution
D006046:Gold