QDs which do not contain any special surface attachments like receptor ligands, targeting peptides or antibodies are called non-functionalised. Nevertheless, these QDs can still contain a shell or be coated with different substances as described in section “exposure / in vitro”.
Such non-functionalised QDs enter cells by endocytosis most often ending up in the cytoplasm. Additionally it could be shown that some types of small nanoparticles can enter the nucleus [^2,6,7]. Furthermore, different coatings of non-functionalised QDs seem to influence their uptake behaviour. The more biocompatible (thus non-toxic) the coating renders the QDs, the less cellular uptake occurs ^[7,8].

QDs may be functionalised by the attachment of specific molecules to the surface as for example antibodies. Such molecules are known as functional groups or moieties. Depending on these functional moieties attached to the QDs surface the mode of entry into the cells as well as the intracellular localisation changes. Using for example QD-labelled antibodies it is possible to stain specifically the plasma membrane or intracellular organelles ^[2]. Another study shows that breast cancer cells could be specifically labelled by CdSe/ZnS QDs linked to immunoglobulin G (a special protein) ^[2,9].

Literature

1. Jaiswal, JK et al. (2003), Nat Biotechnol, 21(1): 47-51.
   
2. Maysinger, D et al. (2007), Eur J Pharm Biopharm, 65(3): 270-281.
   
3. Chan, WC et al. (1998), Science, 281(5385): 2016-2018.
   
4. Chen, F et al. (2004), Nano Letters, 4(10): 1827-1832.
   
5. Voura, EB et al. (2004), Nat Med, 10(9): 993-998.
   
6. Lovric, J et al. (2005), J Mol Med (Berl), 83(5): 377-385.
   
7. Bottrill, M et al. (2011), Chem Commun (Camb), 47(25): 7039-7050.
   
8. Chang, E et al. (2006), Small, 2(12): 1412-1417.
   
9. Wu, X et al. (2003), Nat Biotechnol, 21(1): 41-46.

The longer Cadmium (Cd)-based QDs reside in the body the greater is the chance of coating degeneration, subsequent leakage of Cd²⁺-ions and thus the induction of toxicity at sides of deposition. The clearance of differently sized, modified and coated CdSe/ZnS QDs was systematically analysed in a rat model. The scientists could show that urine excretion was reduced with increasing size of the QDs ^[3]. Bigger particles were not excreted but found in the liver, lung and spleen which correlates well with the above mentioned results. They defined the maximum hydrodynamic diameter for excretion to be 5,5 nm (which is very small!). Furthermore their results demonstrate that positively as well as negatively charged QDs bind to serum proteins and with that largely increase in size up to a diameter of 15 nm.

In conclusion the production of QDs suitable for in vivo applications is complex and sophisticated. On the one hand particles should be as stable as possible to prevent Cd²⁺-ion leakage. This could be achieved by different coatings. But on the other hand, to be cleared from the body QD size should not exceed 5,5 nm which is hardly possible with currently used coatings.

Literature

1. Hardman, R (2006), Environ Health Perspect, 114(2): 165-172.
   
2. Bottrill, M et al. (2011), Chem Commun (Camb), 47(25): 7039-7050.
   
3. Choi, HS et al. (2007), Nat Biotechnol, 25(10): 1165-1170.

It is very challenging to deliver drugs to the brain because the blood brain barrier (BBB) functions as a gatekeeper guarding the brain from exogenous substances.

In a recent study bioconjugated QDs were injected intraperitoneally (meaning into the body cavity) into mice and their distribution in the body was investigated ^[1]. Scientists found, that the QDs reached the blood circulation and mainly accumulated within the spleen, the liver and the kidney (correlating very well with other studies). However, a very small but still considerable amount ended up in the brain. Although most of the particles resided in blood vessels of the liver, the kidney and the brain, a few reached the brain tissue.

Literature

1. Kato, S et al. (2010), Nanotechnology, 21(33): 335103.

Under certain conditions this coating can be lost, which can lead to leaching of toxic heavy metals. Part of these dissolved metals could be bound by numerous compounds present in the environment (dissolved organic materials, proteins) and are therefore no longer available for organisms ^[1,2].

Depending on the type of organic coating, agglomeration and sedimentation of the QDs occur under specific environmental conditions ^[1]. Quantum Dots interact with compounds present in the environment (dissolved organic materials, alginates, metal ions), which either bind to the particles, change their agglomeration and sedimentation behaviour, or restrict the fluorescence of the particles ^[3,4]. Quantum Dots can slow down the microbial decomposition of dead organic materials in the environment ^[5]. In general, when present in the environment over longer periods of time, the particles seem to dissolve and release e.g. Cadmium ions ^[6].

Literature 

1. Mahendra S. et al., 2008, Environ Sci Technol, 42, 9424-9430 .
   
2. Lee S et al., 2011, J Nanopart Res, 13, 3051-3061 .
   
3. Slaveykova VI and Startchev K, 2009, Environ Pollut 157, 3445-3450 .
   
4. Zhang Y et al., 2008 Environ Sci Technol, 42, 321-325 .
   
5. Gao J et al., 2011, J Hazard Mater, 186, 940-945 .
   
6. Pace, HE et al., 2010, ETC, 29, 1338-1344 .