Structural Biochemistry/Quantum Dot-Aptamer Conjugate
Nanomedicine is really an interdisciplinary subject. It includes subject such as Nanoengineering, chemical engineering, bioengineering, chemistry, material science, biology, physics, pharmacy, and medicine. In order to ensure a drug is effectively taken place inside the body, the biological system, the chemical reactivity of the drug, and the physical transportation inside the body must be well considered. Nanomedicine is a field that is being heavily studied in recent decades. There are more and more innovative ways to make an already known drug more effective, such as combining a drug with two or three materials to achieve a goal that just drug alone cannot achieve.
Example Quantum Dot – Aptamer Conjugates In cancer treatment, it is important to see whether the cancer drug is killing tumor tissue or normal healthy tissue. Therefore, imaging is an important application. Fluorescent and quantum dots are two good indicators. Quantum dots, a type of semiconductor nanocrystal that functions similarily as fluorescent, has been increasingly utilized in biological system and labeling due to their unique optical properties, including board range of absorption with narrow photoluminescence spectra, high quantum yield, low photobleaching, and resistance to chemical degradation. The surface of quantum dot can be modified such that antibodies, aptamers, or peptide bonds can be attached to it. Now this complex exhibits several properties that are useful for cancer therapy.
The specific example given here comprises of quantum dots, aptamers, and doxorubicin conjugate (as the schematic shown below) that targets and kills prostate cancer cells. The quantum dot fluorescent functions as an imaging tool. One end of the RNA aptamers attaches to the surface of quantum dot and the other end attaches to doxorubicin. This aptamer also functions as an active ligand that targets cancer cells. Lastly, doxorubicin is a well-known cancer therapeutic agent that also has slight fluorescent property. The fluorescent of doxorubicin is too weak to be detected; therefore, it is not viable. However, if quantum dots are used, the fluorescent signal inside thin human body tissue can be detected.
When the quantum dot is by itself, it has a fluorescent color of green. That is known as the “on” state. In order to temporarily “turn off” the fluorescent of quantum dot, the fluorescent property of doxorubicin becomes crucial in this conjugate. When two materials both exhibit a fluorescent property are close together, they “quench” each other. In this case, they can temporarily disable the fluorescent property of each other. Doxorubicin exhibits a red fluorescent, while this specific quantum dot exhibits a green fluorescent. When the two form a conjugate, the two colors are able to “cancel” each other. The ratio to cancel doxorubicin to quantum dot is approximately 8 to 1.
Before this conjugate enters the cancer cell, this conjugate is in the “off” state. When the conjugate is being transported to the tumor site in blood streams by both convection and diffusion, the conjugate is able to target tumor cell due to the aptamer ligands on the conjugate. After the conjugate enters through endocytosis into the tumor cell, the conjugate is sent to lysosome. The lysosome is able to digest aptamer, breaking the conjugate. The release of doxorubicin recovers the fluorescent property of the quantum dot back to the “on” state, enabling imaging and detection. The released doxorubicin moves to the nucleus to kill the cancer cell. The figure shown below is a schematic of the conjugate inside the cancer cell.
This innovative conjugate is able to not only target the cancer cell but also provide imaging inside the cancer cell. There are numerous other methods that is yet to be discovered to achieve more effective targeted drug delivery.
Bagalkot, Vaishali, Liangfang Zhang, Etgar Levy-Nissenbaum, Sangyong Jon, Philip W. Kantoff, Robert Langer, and Omid C. Farokhzad. "Quantum Dot−Aptamer Conjugates for Synchronous Cancer Imaging, Therapy, and Sensing of Drug Delivery Based on Bi-Fluorescence Resonance Energy Transfer."Nano Letters 7.10 (2007): 3065-070. Print.