Introduction of Quantum Dots
Quantum dots (QDs) are nanometer-scale semiconductor materials. They range from 1 to 100 nanometers in size, and have tunable optical properties, depending on the size of the QD. This size-dependent optical property shows much promise in biomedicine, such as bioimaging, drug delivery, and biosensing. QDs have high brightness, a narrow emission spectrum, and long-term photostability, but also have excellent surface modifiability for binding biomolecules.
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Basic Properties and Synthesis Methods of Quantum Dots
Physicochemical Properties of Quantum Dots
The size of QDs can be precisely controlled, which is one of the most important advantages. Under well-controlled synthesis conditions, QDs with an average size between 1 and 100 nanometers can be prepared. The wavelength of the emitted light can be controlled by controlling the size of the QDs. The quantum confinement effect gives QDs excellent optical properties, including high brightness, narrow emission spectrum, and long photostability, which is far superior to conventional organic dyes in bioimaging.
In addition, the surface of QDs can be modified, which has also led to their extensive applications. Surface functionalization allows for conjugation of QDs with biomolecules such as antibodies, peptides, and DNA, which can be used for targeted delivery and imaging.
The researchers conjugated a HER2 antibody scFv fragment to liposomes and quantum dots to successfully prepare traceable immunoliposomes (QD-ILs) for targeted drug delivery to breast cancer cells.
Synthesis Methods
QDs can be synthesized through organometallic methods, hydrothermal methods, and microwave-assisted methods. Colloidal synthesis is one of the most common used methods. The precursors are injected into an organic or aqueous system and molecular assembly is promoted at a high temperature to form nanocrystals. The growth of the materials can be controlled by changing the process parameters which in turn results in QDs of a defined size, shape, and composition with optical properties of a particular design.
Biological templates and electrochemical assembly are other important synthetic routes. The biological template method uses a biomolecule as the template. The biomolecules help to control the structure of the QDs that are grown. Electrochemical assembly uses the electric field to cause the self-assembly to occur and has also been used in the preparation of QDs with the required morphologies.
Bottom-up synthesis methods include the wet chemical methods and vapor phase methods, and the top-down processing methods involve a method such as electron beam lithography. Bottom-up synthesis methods are not very costly but impurities can be introduced in the QDs as byproducts. Top-down processing techniques are complex and expensive.
Applications of Quantum Dots in Bioimaging
Applications of Quantum Dots in Cellular Imaging
The primary cell imaging application of quantum dots is as fluorescent probes. Brighter than traditional organic dyes, and more photostable, quantum dots can be used for single molecule imaging, to probe the molecular motion and dynamic process of molecules in cells.
Single molecule imaging: Specific biomolecules (such as antibodies, DNA) can be conjugated to quantum dots to label specific proteins or molecules in cells for specific targeting and tracking, so as to study the fine structure and function of cells.
Live cell imaging: Quantum dots can be introduced into living cells for long-term imaging without affecting the normal function of cells. For example, quantum dots combined with folic acid for cancer cell detection, so as to achieve targeted imaging.
Multicolor imaging: The emission wavelength of quantum dots can be tuned by controlling the size of the quantum dots, and quantum dots of different colors can be used for multiple labeling, so as to track the dynamic behavior of multiple target molecules at the same time. This has important application value in cell biology, tumor research and other fields.
Applications of Quantum Dots in In Vivo Imaging
The most widely used method of quantum dots in vivo imaging is via the encapsulation of quantum dots in phospholipid microspheres, which can improve biocompatibility and targeting. Encapsulated quantum dots can be stable in vivo and can be delivered to the target tissue or organ through the circulatory system.
Tumor-Targeted Imaging: Tumor specific receptors (e.g., integrins) can be targeted by quantum dots to image tumor angiogenesis and the presence of molecular markers in tumor microenvironments.
Vascular Imaging: Quantum dots can be used for vascular imaging as well, such as the integrin binding of quantum dots to image tumor angiogenesis for the purpose of determining the blood supply of a tumor by a physician.
Imaging in Small Animal Models: Quantum dots have been used for in vivo molecular and cellular imaging in mouse models. Quantum dots were intravenously delivered to specific tissues in mice and their in vivo distribution and metabolism were determined.
Applications of Quantum Dots in DNA Sequencing
The main role of quantum dots in DNA sequencing is as DNA probes. Quantum dots that are bound to a DNA molecule can be used for highly sensitive biological detection (gene transfer, biosensing etc. ).
DNA probes: Quantum dots bound to DNA molecules can label specific DNA sequences for highly sensitive DNA detection.
Gene transfer: Quantum dots can be used as gene carriers that can deliver genes to specific cells or tissues, which is the basis of gene therapy.
Biosensing: Quantum dots can bind to biomolecules (for example, urease) for the detection of specific molecules in biological samples (they have been used in the early detection of NSCLC).
Applications of Quantum Dots in Drug Delivery
Drug Carriers
The application of quantum dots in drug delivery is primarily reflected in their ability to act as drug carriers. Through surface modification, quantum dots can improve the biocompatibility and targeting of drugs, thereby enabling precision therapy.
Targeted delivery of anticancer drugs: Quantum dots can be combined with anticancer drugs (such as doxorubicin) for targeted delivery to tumor cells, thereby improving drug efficacy and reducing side effects.
siRNA delivery: Quantum dots can be combined with siRNA to inhibit the expression of pathogenic genes, thereby achieving gene silencing therapy.
Photothermal therapy: Quantum dots can also be combined with other therapeutic approaches (such as photothermal therapy or photodynamic therapy) to achieve even stronger therapeutic effects.
Design of Multifunctional Nanocomplexes
In order to further improve the drug delivery performance and targeting, researchers have also constructed multifunctional nanocomplexes by combining quantum dots with other drug delivery systems (liposomes, magnetic nanoparticles, etc.) for multifunctional combination.
Liposome complexes: The combination of quantum dots and liposomes can improve the bioavailability and targeting of drugs, and also reduce the toxicity and side effects of drugs.
Magnetic nanoparticle complexes: Quantum dots can be combined with magnetic nanoparticles for controlled release and targeted delivery of drugs, so as to improve the therapeutic effect.
Multimodal imaging: Quantum dots can be combined with MRI contrast agents for multimodal imaging, which can be used for dynamic monitoring of drug activity in the body.
Quantum Dots for Personalized Medicine
With the development of precision medicine, the application of quantum dots in personalized medicine has also gradually become a research hotspot. Quantum dots can be used to target disease biomarkers to improve the accuracy of diagnosis and treatment, thus achieving personalized treatment.
Targeted disease biomarkers: Quantum dots can be used to target disease biomarkers (such as specific proteins or receptors) for targeted delivery of drugs or diagnostic reagents.
Customized drug delivery systems: Quantum dots can be used to develop customized drug delivery systems in the future. The release rate and targeting of drugs are adjusted according to the patient's specific condition to achieve more accurate treatment.
