Highly luminescent semiconductor quantum dots (zinc sulfide-capped cadmium selenide) have been covalently coupled to biomolecules for use in ultrasensitive biological detection. In comparison with organic dyes such as rhodamine, this class of luminescent labels is 20 times as bright, 100 times as stable against photobleaching, and one-third as wide in spectral linewidth. These nanometer-sized conjugates are water-soluble and biocompatible. Quantum dots that were labeled with the protein transferrin underwent receptor-mediated endocytosis in cultured HeLa cells, and those dots that were labeled with immunomolecules recognized specific antibodies or antigens.

We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).The chemical design and synthesis of nanoparticles have fueled the growth of nanotechnology. The foundation of nanotechnology research is based on the size and shape of the structures, where distinct optical, electronic, or magnetic properties can be tuned during chemical synthesis. There is an enormous interest in exploiting nanoparticles in various biomedical applications since their size scale is similar to that of biological molecules (e.g., proteins, DNA) and structures (e.g., viruses and bacteria). Furthermore, useful properties can be incorporated into the design of the nanoparticles for manipulation or detection of biological structures and systems. Nanoparticles are currently used in imaging, 1-6 biosensing, 7-9 and gene and drug delivery. 10-12As the field continues to develop, quantitative and qualitative studies on the cellular uptake of nanoparticles, with respect to their size and shape, are required in order to advance nanotechnology for biomedical applications. This will be important for assessing nanoparticle toxicity (i.e., if nanoparticles do not enter cells, they are less prone to killing cells or altering cellular function), for advancing nanoparticles for imaging, drug delivery, and therapeutic applications (i.e., how to maximally accumulate nanoparticles in cells, tumors, and organs?), and for designing multifunctional nanoparticles (i.e., are there dimensional limits to designing nanoparticles that can target and kill diseased cells?). Detailed studies of uptake kinetics of nanoparticles by cells have not been well characterized and quantified as a function of their size and shape (i.e., trends have not been determined). Most studies have focused on liposomes [13][14][15][16] and polymer particles, 17,18 which are generally larger than 100 nm. Furthermore, metallic, semiconductor, and carbon-based nanoparticles can be synthesized with greater size and shape variabilities than liposome and polymer particles.We selected gold nanoparticles as the model system for our studies; the rationale being that gold nanoparticles could be synthesized at a large size (1-100 nm diameter) and shape range (1:1 to 1:5 aspect ratio). Gold nanoparticles are also easy to characterize by the techniques of UV-vis spectrophotometry, inductively coupled plasma atomic emission spectroscopy (ICP-AES), and transmission electron microscopy (TEM). Furthermore, gold nanoparticles have recently been demonstrated...

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With their bright, photostable fluorescence, semiconductor quantum dots show promise as alternatives to organic dyes for biological labeling. Questions about their potential cytotoxicity, however, remain unanswered. While cytotoxicity of bulk cadmium selenide (CdSe) is well documented, a number of groups have suggested that CdSe QDs are cytocompatible, at least with some immortalized cell lines. Using primary hepatocytes as a liver model, we found that CdSe-core QDs were indeed acutely toxic under certain conditions. Specifically, we found that the cytotoxicity of QDs was modulated by processing parameters during synthesis, exposure to ultraviolet light, and surface coatings. Our data further suggests that cytotoxicity correlates with the liberation of free Cd ions due to deterioration of the CdSe lattice. When appropriately coated, CdSe-core QDs can be rendered non-toxic and used to track cell migration and reorganization . Our results inform design criteria for the use of QDs in vitro and especially in vivo where deterioration over time may occur.

An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices. Here, we provide rationales for these studies, review the current progress in studies of the interactions of nanomaterials with biological systems, and provide a perspective on the long-term implications of these findings.