Nanotechnology & Nanobiotechnology Nanotechnology, in simple terms, means the study and exploitation of tiny objects, whose dimensions are just a few molecules and atoms. In strict scientific terms, nanotechnology concerns physical dimensions ranging from 1-100 nm (1 nm = 10-9 m = 10 atoms wide) down to 1 nm. Nanobiotechnology is the application of nanotechnology to the life sciences: The technology encompasses precision engineering as well as electronics, and electromechanical systems as well as mainstream biomedical applications in areas as diverse as gene therapy, drug delivery and novel drug discovery techniques.

LEADING SEGMENTS IN NANOBIOTECHNOLOGY Demand for more advanced technologies and innovations in nanomaterials have created three major segments within nanobiotechnology: Drug delivery Biosensors Imaging agents

Drug Delivery Till early 1970, drugs were delivered to the human body exclusively via oral and intravenous (靜脈內的) means. Disadvantages: High doses of drug cannot be injected into the body at one time. Intravenous (靜脈內的) delivery leads to high concentration of drug into the blood stream and can create toxic side effects. Only a very small percentage of the injected drug reaches the affected area in the body and hence multiple injections are often required for effective treatment.

Delivery vehicle & Method of administration Construct of the drug : Delivery vehicle & Method of administration New Drug Delivery Vehicles: Organic and synthetic polymers, and other chemical constructs that can release drugs at a sustained rate, or release them only in certain environments 2. Liposome New Methods of Administration: Medicated skin patches Implanted devices that can release drugs with an external remote control Powder forms of traditional drugs which can be inhaled and absorbed through the lungs.

Liposomes encapsulate active drugs to improve their delivery Liposomes encapsulate active drugs to improve their delivery. Depending on the construction of the liposome, the active drug can be carried within its layers or in the hallow space created by the encapsulation. Liposomes mimic the natural phospholipid cell membranes in the human body. The immune system, which seeks out foreign material for destruction, can be a major obstacle to liposomes. In 1992, researchers discovered that coating liposomes with inactive polymers, such as polyethylene glycol (PEG), drastically increased the liposome's ability to evade recognition by the immune system. The main mechanism of a liposome is simply fusing to the cell membrane or through endocytosis.

Drug Delivery Systems in Development The creation of vehicles or constructs that can target the disease tissue more accurately: Smart Drugs – are designed to work only when activated by certain components in the body. For example, a smart drug designed to be activated by a certain enzyme will be activated only in tissues that produces that specific enzyme. Monoclonal Antibodies – These are antibodies (抗體) made in the lab that can target antigens (抗原) with extreme specificity. They are attached to a drug in order to guide it to a specific cell. For example, cancer drugs can be attached to monoclonal antibodies made against tumour cells, which helps the drug target only tumour cells. This reduces the toxic effects of cancer drugs.

Antibody (抗體) & Antigen (抗原) Antibodies (ab) are proteins that attach to foreign material in the body (such as bacteria and viruses) and are released by certain cells of the immune system. They "mark" these foreign material for removal or destruction by other components of the immune system. Any foreign substance that can make the immune system release antibodies is called an antigen (ag). For example, a flu virus is an antigen because it makes the immune system release antibodies. Antibodies are unique because they are made in response to specific antigens. In fact, antigens and antibodies fit like puzzle pieces. For example, a particular type of flu virus prompts the immune system to produce antibodies that fit that particular type of flu virus. ab + ag = ab-ag

Biosensors Biosensor = bioreceptor + transducer Transducer: a device that transfers or translates energy from one kind of a system to another. For example, a transducer can transfer a thermal signal into an electrical signal.

Bioreceptor is a biomaterial or a biomimic that recognizes the target analyte: tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids etc. Transducer or transducing microsystem converts the recognition event into a measurable signal : optical, electrochemical, thermometric, piezoelectric or magnetic. 

Specific interactions between the target analyte and recognition sites within the bioreceptor produces a physico-chemical change which is detected and may be measured by the transducer.  In principle, any biomolecule or molecular assembly that has the capability of recognizing the analyte can be used as a bioreceptor.

Specificity  -remarkable ability to distinguish between the analyte of interest and similar substances.  -measure specific analytes with great accuracy.  Speed  -the analyte tracers or catalytic products can be directly and instantaneously measured. -no need to wait for results from lengthy procedures carried out in centralised laboratories.   Simplicity  -one single sensor. -enables the measurement of target analytes without using reagents. For example, the glucose concentration in a blood sample can be measured directly by a biosensor (which is made specifically for glucose measurement) by simply dipping the sensor in the sample. This is in contrast to the conventional assay in which many steps are used and each step may require a reagent to treat the sample.  Continuous monitoring capability  -can regenerate and reuse the immobilized biological recognition element. For enzyme-based biosensors, an immobilized enzyme can be used for repeated assays

Applications of Biosensors Clinical diagnosis and biomedicine  Farm, garden and veterinary analysis  Process control: fermentation control and analysis  Food and drink production and analysis  Microbiology: bacterial and viral analysis  Pharmaceutical and drug analysis  Industrial effluent control  Pollution control and monitoring  Mining, industrial and toxic gases  Military applications 

Imaging agents Magnetic Resonance Imaging (MRI) Near-Infrared Fluorescence Imaging (NIRF) Combined with MRI Drug Discovery Rapid Ex-Vivo Diagnostics

 Domains enriched in cholesterol (膽固醇) and sphingolipids Lipid Rafts  Domains enriched in cholesterol (膽固醇) and sphingolipids Lipid rafts are thought to be in liquid-ordered (lo) phase ( lo-phase lipid “island” floats in the lc-phase lipid “sea”.) Lipid rafts are postulated to be very important in signal transduction in cells (as signaling platforms, for example). Size of raft domain: 0 - 700 nm Fraction of lipid rafts in cell membranes

Yuan et al., 2002 Raft marker