Quantum Dots for Therapeutics and Diagnostics

Quantum dots with single functions or multifunctional nanoplatforms can be designed to implement therapeutic and diagnostic modalities.

Though some nanoparticles are used to implement single functions, the combination of certain drugs and QDs enables the design of multifunctional nanoplatforms that carry out the tasks of targeting, therapeutics and imaging at molecular level.

This article explains how QDs can be used for theranostics (a new medical word built from two words: diagnostics and therapeutics). These procedures provide the opportunity to evaluate in real time any type of molecular damage and to deliver the required medication in the affected area.

The advantage that clinical applications designed with QDs have in comparison to traditional therapies is that with this technology treatments can be specifically tailored to patient’s needs. In other words QD probes and biosensors allow for the personalization of therapies, a facility that will dramatically improve medicine in the years to come.

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Main Characteristics

It is important to bear in mind that QDs present a series of common characteristics that makes them suitable as theranostics systems.

They can be designed to target only specific cells. Capable of entering the cells, they generate variable levels of cytotoxicity (poisoning of the cytosol – liquid inside the cell). They can also penetrate the barriers within the cells facilitating intracellular trafficking, therefore entering in organelles (cells organs). These nanoparticles may be constructed with in-built capabilities that allow them to channel a therapeutic agent once they have reached the damaged area. Also they include an optical or magnetic agent that can provide real time assessment of the treatment given.

QDs with Single Functions

There are nanoparticles that carry out single functions, for example the detection of metastatic cancer cells. These unconjugated QDs can be delivered into the cell via non-specific endocytosis, transfection agents, electroporation, microinjections or needles penetrating the cell membrane.

Non-specific endocytosis means that nanoparticles are engulfed by the cell through a process where the plasma membrane invaginates and encloses the particles in a vesicle. This produces cellular internalization of that construct, and thus this vesicle passes through the cell wall and arrives in the cytoplasm

Transfection agent delivery is a more efficient tactic than non-specific endocytosis. It is the process through which nanoparticles are transferred to the plasma membrane inside a liposome, micelle or polymer and then endocytosed until they reach the cytoplasm. In this case there are fewer aggregations. It is easier to observe QDs within the cell.

Electroporation is the opening of the plasma membrane pores using an electric field that converts the membrane into a permeable layer. After a few seconds it reseals itself. Electroporation permits the delivery of QDs directly into the cell in order to increase gene expression (it makes easier to define the relevant genes). Setting the optimal electric field strength and the pulse length parameters is of paramount importance. These values need to be determined empirically (estimations based on observations and experiments conducted in a lab rather than theory).

Finally microinjections or needle penetration are produced by injecting QDs directly into the nucleus and cytoplasm. In this case there is no enzymatic degradation, that is to say: there are no vesicles (endosomes) formed by endocytosis whose content is deactivated later on in lysosomes. In fact, the use of needles spreads nanoparticles directly into the cell instead of inside a vesicle, making possible entry even into the nucleus.

It is important to note that the use of needles requires high levels of physical precision. Unfortunately, this system may produce irreversible damage to certain cells.

Multifunctional Quantum Dots

These developed nanoparticles are complex molecules that can be built by conjugating QDs with aptamers, a therapeutic agent such as a drug, and a targeting ligand (a substance that binds to another molecule to form a larger biochemical complex), a peptide (an organic molecule made out of two or more amino acids), an antibody or a protein. The loading of the drug and further release in the damaged area is mediated by the use of Forster Resonance Energy Transfer (FRET).

These multimodal nanoplatforms enter the cells containing what is known as stimuli-sensitive nano-antennae. These are particles that can be sensitive to pH (acidity), temperature or enzymes and, induced by stimuli that affect the factors previously mentioned, the release of the drug can be triggered in a specific section of the cell.

A known example carried out “in vitro” of a multifunctional nanoparticle is the QD-aptamerApt-doxorubicin conjugate (doxorubicin is an anthracycline drug used to treat several types of cancer). Another system utilized “in vivo” is the QD-L (liposome) complex. This latter integration produces lower cytotoxicity levels. In addition, there are other polymeric gene carriers that can be assembled with nanoparticles.

Microfluidics-based synthesis

Many research teams are investigating the physicochemical properties of QDs such as size, surface charge and surface coating materials. It has been demonstrated that the toxicity of nanoparticles depends on these values. Therefore one of the main targets that needs to be achieved in order to proceed with QDs as common theranostic instruments in the clinical environment is to convert them into non-toxic biosensors. Perhaps one of the systems to achieve minimum toxicity levels is microfluidics-based synthesis.

This technique is an alternative system that allows the manufacture of miniaturized devices (at a nano scale) such as lab-on-chips, through the manipulation of fluids. This process empowers scientists to control the size, shape, functionality and other characteristics of the nanoparticles they synthesize, maintaining uniform microenvironments.

Sources

Ho, Yi-Ping. and Leong, W Kam. "Quantum dot-based theranostics", Nanoscale, Vol 2