**5. Cadmium-containing quantum dots as a platform for nanoparticle drug delivery vehicle design**

and traceable drug delivery. However, high-quality QDs are mainly made with heavy metals, like cadmium, whose long-term toxicity is currently largely unknown. Despite this limitation, QDs have been applied to cells and small animals as drug carriers, serving as an outstanding discovery tool for drug screening and validation, and as prototype materials for drug carrier engineering [75]. One primary challenge of drug delivery is maintaining a useful concentration

Pharmacokinetic Properties and Safety of Cadmium-Containing Quantum Dots as Drug Delivery Systems

http://dx.doi.org/10.5772/58553

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Nanoparticle-based drug delivery is on its way to overcoming the fundamental limitations of simple free drug formulations, providing means to change their pharmacological properties and also understand their biological fate in great detail. Among many contrast agents for studying nanoparticle-based drug delivery vehicles, QDs are particularly suitable. Their unique amalgamation of useful features, such as small size, versatile surface chemistry, and exquisite optical properties make them an ideal platform for the comprehensive characteriza‐ tion of nanoparticle-based drug delivery vehicle behavior across single-cell to whole organism levels. In this new field, QDs have already made substantial contributions, enabling dynamic monitoring of nanocarrier cell uptake, intracellular distribution, circulation half-times, and biodistribution. Early on, the design of QDs drug delivery vehicles was governed by the intrinsically poor pharmacokinetic (PK) properties of conventional drugs. Low drug solubility, rapid metabolism and clearance and, most importantly, a lack of selectivity, regularly lead to therapeutic failure by causing severe systemic toxicity in healthy tissues, thus prohibiting the dose escalation necessary to eliminate tumor cells. Incorporating these drugs into nanocarriers offers an exciting opportunity to redefine the PK properties, improving therapeutic efficacy

When we utilize a nanopharmaceutical, it is important to realize that, in contrast to delivering a drug that is an organic molecule, we are delivering something of a discrete entity in a nanoparticle-comprised of atomic scale parts. Due to the quantum effects and electronic interactions that predominate at the nanoscale, we need to alter the way in which we think about pharmacological parameters in order to adapt to nanoscience. Nanopharmacology is further complicated by the need to establish the behavior of nanoparticles such as QDs within the traditional pharmacological parameters of absorption, distribution, metabolism and excretion (ADME). Nanoconstructs, in many cases, have limited metabolism and excretion and persist in biological systems; this becomes particularly important when toxic atoms such as cadmium are involved. The pharmacological parameters of the behavior of cadmiumcontaining quantum dots in biological systems is currently still under investigation. Dosing parameters, absorption, distribution, metabolism and excretion require considerable further

The first factor we need to establish before we study the pharmacokinetics parameter is the dose. Adequate estimates of QDs exposure during treatments such as cancer therapy must be in place so that both pharmacological and toxicological studies can be conducted within a

study, since we have little information on these parameters at this point.

of the drug in the targeted tissue while preventing toxicity.

and reducing side effects.

**6. Pharmacokinetics of cadmium-containing quantum dots**

Recently, there has been an explosion in the development of nanoparticle-based drug delivery vehicles composed of lipids, polymers, carbon materials, and even hybrid combinations of those materials tailored not only for the dramatic improvement of the pharmacological properties of existing drugs, but also for enabling the delivery of new classes of potent anticancer drugs for gene therapy and immunotherapy [67, 68]. With QDs, a combination of unique physical, chemical, and optical properties facilitates in-depth study of nanocarrier interactions with biological systems through real-time monitoring of QDs biodistribution, intracellular uptake, drug release, and long-term nanocarrier fate. At the same time, compact size and compatibility with a variety of surface modification strategies enables substitution of virtually any QD core with a QD within single-nanoparticle drug delivery vehicles, or incorporation of QD tags within larger multicomponent vehicles. The combination of superior brightness and resistance to photo-degradation represents another set of QD properties that highly useful for long-term nanocarrier tracking.

The great interest in engineering NP-based drug delivery vehicles is driven by the powerful capability of nanocarriers to completely redefine the pharmacokinetic properties of virtually any drug, ranging from small-molecule therapeutics to large proteins and DNA plasmids. Encapsulation of the drug within the nanoparticles keeps it shielded from the biological environment until the moment of carrier degradation and drug release, thus minimizing nonspecific and potentially adverse interactions en route to the target [69].

A few reports have appeared recently regarding this ambitious goal. It has previously conjugated captopril, an antihypertensive drug, to the QD surface and studied its pharmaco‐ dynamics and pharmacokinetics in stroke-prone spontaneously hypertensive rats [70]. The results show that the administered QD-captopril conjugates are capable of decreasing rat blood pressure to the same extent as the captopril alone in the first 30 min, but the therapeutic effect of QD-captopril disappears after 60 min. It is unclear whether the therapeutic effect results from the QD-captopril conjugates or captopril molecules detached from the QD surface. Another piece of interesting work was previously reported, wherein a targeting functionality was added to QDs by linking them with RNA aptamers (A10) that specifically bind to prostate specific membrane antigen (PSMA) [71]. Doxorubicin, a DNA-interacting drug widely used in chemotherapy, was immobilized onto QDs by intercalation within the A10 RNA aptamer [72]. Another study reported the ability of nanoconjugates of CdSe/CdS/ZnS and doxorubicin (Dox) to target alveolar macrophages, cells that play a critical role in the pathogenesis of inflammatory lung injuries. The results demonstrated that nanoparticle platforms can provide targeted macrophage-selective therapy for the treatment of pulmonary disease [73]. This was previously reported regarding siRNA delivery using QDs as delivery vehicles [74].

QDs already play an important role in fundamental biology and *in vitro* disease diagnostics and prognostics. Their unique structural and surface properties, such as their tunable and uniform size, flexible drug-linking and doping mechanisms, large surface-to-volume ratio and wide spectrum of surface reactive groups have enabled a new avenue of research: targeted and traceable drug delivery. However, high-quality QDs are mainly made with heavy metals, like cadmium, whose long-term toxicity is currently largely unknown. Despite this limitation, QDs have been applied to cells and small animals as drug carriers, serving as an outstanding discovery tool for drug screening and validation, and as prototype materials for drug carrier engineering [75]. One primary challenge of drug delivery is maintaining a useful concentration of the drug in the targeted tissue while preventing toxicity.
