yulius hermanto
Concept of Nanomedicine
Introduction
Nowadays, we already improved our knowledge of medicine, including the concept of the disease pathogenesis. Most of the diseases that we face recently can be explained as an alterations in biologic processes at the molecular or nanoscale level. Wheter it caused by external (such as infection) or internal (such as mutated genes).
Gene mutations, abnormal proteins, and infections caused by viruses or bacteria can lead to cell malfunction or miscommunication, sometimes leading to life-threatening diseases. Infectious agents and molecules changes in nucleus are nanometers in size and may be located in biologic systems that are protected by nanometer-size barriers. Their chemical properties, size, and shape appear to dictate the transport of molecules to specific biologic compartments and the interactions between molecules.
Nanomedicine is defined as the “intentional design, characterization, production, and applications of materials, structures, devices, and systems by controlling their size and shape in the nanoscale range (1 to 100 nm) for the diagnosis and treatment of diseases at the molecular level.
Nanomaterials are being designed to aid the transport of diagnostic or therapeutic agents through biologic barriers or to gain access to molecules; to mediate molecular interactions; and to detect molecular changes. Compare with atoms and macroscopic materials, nanomaterials have a high ratio of surface area to volume as well as tunable optical, electronic, magnetic, and biologic properties, and they can be engineered to have different sizes, shapes, chemical compositions, surface chemical characteristics, and hollow or solid structures. These properties are being incorporated into new generations of drug-delivery vehicles, contrast agents, and diagnostic devices.
Properties of Nanomaterials
An understanding of these fundamental physical and chemical properties is necessary for the optimal use of nanomaterials in medical applications. Nanomaterials consist of metal atoms, nonmetal atoms, or a mixture of metal and nonmetal atoms, commonly referred to as metallic, organic, or semiconducting particles, respectively. The surface of nanomaterials is usually coated with polymers or biorecognition molecules for improved biocompatibility and selective targeting of biologic molecules. The final size and structure of nanomaterials depend on the salt and surfactant additives, reactant concentrations, reaction temperatures, and solvent conditions used during their synthesis.
Unique aspects of metal-containing materials are their size, shape, and composition-tunable electronic, magnetic, and optical properties. This relationship is a direct consequence of the behavior of electrons in the nanomaterial. Electrons have two important characteristics: their spin and their ability to move in a quantized fashion between specific energy levels. Electrons are similar to tiny bar magnets, with a surrounding magnetic field that corresponds to the electron spin in an applied field. Also, after absorbing energy, electrons can generate light or heat when they move between different energy levels.
In macrostructures, electrons can spin in two directions, in opposition or in alignment, and can move among many energy levels. The behavior of electrons in nanostructures is more constrained and depends on the size or shape of the material or on the electrons' interactions with the surface coating. The chemical composition of a nanomaterial determines whether one or both electron characteristics (spin and energy transition) are affected, as well as the extent of that effect.
Nanomaterials Applications in Medicine
Many of these nanomaterials are designed to target tumors in vivo and are intended for use either as drug carriers for therapeutic applications or as contrast agents for diagnostic imaging. Nanomaterials infused into the bloodstream can accumulate in tumors owing to the enhanced permeability and retention effect when the vasculature of immature tumors has pores smaller than 200 nm, permitting extravasation of nanoparticles from blood into tumor tissue. The infusion of antineoplastic drugs with nanomaterials as carriers results in an increased payload of drugs to the tumor, as compared with conventional infusion. With nanomaterials, the high ratio of surface area to volume permits high surface loading of therapeutic agents; in the case of organic nanomaterials, their hollow or porous core allows encapsulation of hundreds of drug molecules within a single carrier particle. When the carrier particle degrades, the drug molecules are released, and the rate of degradation can even be controlled and fine-tuned according to the polymer composition. These nanomaterial delivery vehicles can also be coated with polymers, such as polyethylene glycol, to increase their half-life in the blood circulation, prevent opsonizing proteins from adhering to the nanomaterial surface, and reduce rapid metabolism and clearance. Moreover, the use of nanomaterials for drug delivery may minimize adverse effects by preventing the nonspecific uptake of therapeutic agents into healthy tissues.
Nanoparticles are also attractive as sensitive contrast agents for cancer imaging. On nanoparticle-enhanced MRI, a contrast can be observed between tissues with and those without superparamagnetic iron oxide nanoparticles (SPIONs). In one study, dextran-coated SPIONs were injected into patients with prostate cancer to detect possible lymph-node metastases.17 The dextran coating increased the circulation time of the nanoparticles, and because of their small size, these particles could traverse the lymphatic vessels to reach the lymph nodes and be taken up by the resident macrophages. The use of SPIONs with MRI, as compared with conventional MRI, was associated with substantial increases in both diagnostic sensitivity (90.5% vs. 35.4%) and specificity (97.9% vs. 90.4%) in the detection of metastatic tumors.
Take Home Message
To translate these applications into clinical use, researchers must optimize the nanomaterials, beginning with small-animal models and scaling up to nonhuman primate models — a process that will take some time. These studies should provide a solid foundation for the long-term advancement of nanotechnology into an effective new area in clinical medical practice.
Nowadays, we already improved our knowledge of medicine, including the concept of the disease pathogenesis. Most of the diseases that we face recently can be explained as an alterations in biologic processes at the molecular or nanoscale level. Wheter it caused by external (such as infection) or internal (such as mutated genes).
Gene mutations, abnormal proteins, and infections caused by viruses or bacteria can lead to cell malfunction or miscommunication, sometimes leading to life-threatening diseases. Infectious agents and molecules changes in nucleus are nanometers in size and may be located in biologic systems that are protected by nanometer-size barriers. Their chemical properties, size, and shape appear to dictate the transport of molecules to specific biologic compartments and the interactions between molecules.
Nanomedicine is defined as the “intentional design, characterization, production, and applications of materials, structures, devices, and systems by controlling their size and shape in the nanoscale range (1 to 100 nm) for the diagnosis and treatment of diseases at the molecular level.
Nanomaterials are being designed to aid the transport of diagnostic or therapeutic agents through biologic barriers or to gain access to molecules; to mediate molecular interactions; and to detect molecular changes. Compare with atoms and macroscopic materials, nanomaterials have a high ratio of surface area to volume as well as tunable optical, electronic, magnetic, and biologic properties, and they can be engineered to have different sizes, shapes, chemical compositions, surface chemical characteristics, and hollow or solid structures. These properties are being incorporated into new generations of drug-delivery vehicles, contrast agents, and diagnostic devices.
Properties of Nanomaterials
An understanding of these fundamental physical and chemical properties is necessary for the optimal use of nanomaterials in medical applications. Nanomaterials consist of metal atoms, nonmetal atoms, or a mixture of metal and nonmetal atoms, commonly referred to as metallic, organic, or semiconducting particles, respectively. The surface of nanomaterials is usually coated with polymers or biorecognition molecules for improved biocompatibility and selective targeting of biologic molecules. The final size and structure of nanomaterials depend on the salt and surfactant additives, reactant concentrations, reaction temperatures, and solvent conditions used during their synthesis.
Unique aspects of metal-containing materials are their size, shape, and composition-tunable electronic, magnetic, and optical properties. This relationship is a direct consequence of the behavior of electrons in the nanomaterial. Electrons have two important characteristics: their spin and their ability to move in a quantized fashion between specific energy levels. Electrons are similar to tiny bar magnets, with a surrounding magnetic field that corresponds to the electron spin in an applied field. Also, after absorbing energy, electrons can generate light or heat when they move between different energy levels.
In macrostructures, electrons can spin in two directions, in opposition or in alignment, and can move among many energy levels. The behavior of electrons in nanostructures is more constrained and depends on the size or shape of the material or on the electrons' interactions with the surface coating. The chemical composition of a nanomaterial determines whether one or both electron characteristics (spin and energy transition) are affected, as well as the extent of that effect.
Nanomaterials Applications in Medicine
Many of these nanomaterials are designed to target tumors in vivo and are intended for use either as drug carriers for therapeutic applications or as contrast agents for diagnostic imaging. Nanomaterials infused into the bloodstream can accumulate in tumors owing to the enhanced permeability and retention effect when the vasculature of immature tumors has pores smaller than 200 nm, permitting extravasation of nanoparticles from blood into tumor tissue. The infusion of antineoplastic drugs with nanomaterials as carriers results in an increased payload of drugs to the tumor, as compared with conventional infusion. With nanomaterials, the high ratio of surface area to volume permits high surface loading of therapeutic agents; in the case of organic nanomaterials, their hollow or porous core allows encapsulation of hundreds of drug molecules within a single carrier particle. When the carrier particle degrades, the drug molecules are released, and the rate of degradation can even be controlled and fine-tuned according to the polymer composition. These nanomaterial delivery vehicles can also be coated with polymers, such as polyethylene glycol, to increase their half-life in the blood circulation, prevent opsonizing proteins from adhering to the nanomaterial surface, and reduce rapid metabolism and clearance. Moreover, the use of nanomaterials for drug delivery may minimize adverse effects by preventing the nonspecific uptake of therapeutic agents into healthy tissues.
Nanoparticles are also attractive as sensitive contrast agents for cancer imaging. On nanoparticle-enhanced MRI, a contrast can be observed between tissues with and those without superparamagnetic iron oxide nanoparticles (SPIONs). In one study, dextran-coated SPIONs were injected into patients with prostate cancer to detect possible lymph-node metastases.17 The dextran coating increased the circulation time of the nanoparticles, and because of their small size, these particles could traverse the lymphatic vessels to reach the lymph nodes and be taken up by the resident macrophages. The use of SPIONs with MRI, as compared with conventional MRI, was associated with substantial increases in both diagnostic sensitivity (90.5% vs. 35.4%) and specificity (97.9% vs. 90.4%) in the detection of metastatic tumors.
Take Home Message
To translate these applications into clinical use, researchers must optimize the nanomaterials, beginning with small-animal models and scaling up to nonhuman primate models — a process that will take some time. These studies should provide a solid foundation for the long-term advancement of nanotechnology into an effective new area in clinical medical practice.
