Bindu M. Nair

In Vivo Biodistribution of Dendrimers and Dendrimer Nanocomposites — Implications for Cancer Imaging and Therapy

Our results indicate that the surface chemistry, composition, and 3-D structure of nanoparticles are critical in determining their in vivo biodistribution, and therefore the efficacy of nanodevice imaging and therapies. We demonstrate that gold/dendrimer nanocomposites in vivo, present biodistribution characteristics different from PAMAM dendrimers in a B16 mouse tumor model system. We review important chemical and biologic uses of these nanodevices and discuss the potential of nanocomposite devices to greatly improve cancer imaging and therapy, in particular radiation therapy. We also discuss major issues confronting the use of nanoparticles in the near future, with consideration of toxicity analysis and whether biodegradable devices are needed or even desirable.

In vivo toxicity evaluation of gold-dendrimer composite nanodevices with different surface charges

Abstract Composite nanodevices (CNDs) are multifunctional nanomaterials with potential uses in cancer imaging and therapy. Poly(amidoamine) dendrimer-based composite nanodevices are important members of this group and consist of an organic dendrimer component and an incorporated inorganic component, in this case, gold. This study addresses the short- (14 days) and long-term (78 days) in vivo toxicity of generation-5 (G5; 5 nm) PAMAM dendrimer-based gold-CNDs (Au-CNDs) with varying surface charges (positive, negative and neutral) in C57BL/6J male mice. Detailed toxicological analyses of (1) body weight changes, (2) serum chemistry and (3) histopathological examination of 22 organs showed no evidence of organ injury or organ function compromise. Zeta potential of Au-CNDs showed significant change from their parent dendrimers upon gold incorporation, making the normally lethal positive surface dendrimer biologically safe. Also homeostatic mechanisms in vivo may compensate/repair toxic effects, something not seen with in vitro assays.

Toxicity evaluation of gold-dendrimer composite nanodevices in vitro – difference found between tumour and proliferating endothelial cells

Composite nanodevices (CNDs) are a well-studied class of multifunctional nanomaterials with several potential medical uses, including cancer imaging and therapy. Gold/ dendrimer CNDs are organic/inorganic hybrid materials consisting of physical networks of dendrimer(s) and inorganic materials. This design permits properties of dendrimers and inorganic materials to be individually modified and optimized. A detailed understanding of factors regulating toxicity is lacking. We develop and test toxicity assays for CNDs in vitro both for cancer cells and for normal endothelial cells. We show how CND surface charge (positive, negative or neutral) and exposure time affects biosafety for d = 5 nm nanodevices. We also show that formation of the CND (incorporation of gold into a dendrimer template) can lower toxicity of a dendrimer. Interestingly, we also show that tumour cells and proliferating endothelial cells have different toxicity profiles.