Small particles have been in use for biomedical research and in vitro diagnostic protocols during the last fifty years. Polymeric microparticles (specially latex microspheres) obtained as highly monosized assemblies have the advantages of biocompatibility and large reactive surface for biological units. These micro-particles have been adopted by food industry for diagnostics and testing in the production line, such as latex agglutination (LA) for identifying staphylococci, streptococci or Escherichia coli (E. coli). Clinical uses of polymeric microspheres include immunology diagnostics for malignant proliferative plasma cell disorders (i.e., multiple myeloma); immunodiagnostic assay systems using antibody-charged particles for quantification of immunoglobulin molecules in serum or cerebrospinal fluid, and fluorescent neuronal markers for studying the visual cortex. For cancer diagnostics and therapy there are currently a number of techniques based on different types of nanoparticles. Nanotechnological advances are at the bottom of the next paradigm shift in cancer research, diagnostics and therapy by improving direct visualization of malignant cells, targeting at molecular level and safely delivering large amounts of chemotherapeutic agents to desired cells. These techniques should be capable of rapid and sensitive detection of malignant cells at early stages.
The common feature of all nanoparticle-based cancer therapies is the need of specific NPs for achieving the desired therapeutic effect. However, each diagnostic/therapeutic technique requires a different chemical or physical property of the particles involved, which depends on the specific function played by the NPs in that therapy (e.g., vector, porous receptacle, heating agent, magnetic moment carrier, etc…). Sometimes the particle function is activated using an external agent (magnetic fields, light, radiation, etc…) that interacts with the NPs. Therefore the requirements for NPs as biomedical agents span a broad range of novel materials, synthesis strategies, and research fields (see Table).
The common feature of all nanoparticle-based cancer therapies is the need of specific NPs for achieving the desired therapeutic effect. However, each diagnostic/therapeutic technique requires a different chemical or physical property of the particles involved, which depends on the specific function played by the NPs in that therapy (e.g., vector, porous receptacle, heating agent, magnetic moment carrier, etc…). Sometimes the particle function is activated using an external agent (magnetic fields, light, radiation, etc…) that interacts with the NPs. Therefore the requirements for NPs as biomedical agents span a broad range of novel materials, synthesis strategies, and research fields (see Table).
Basic mechanisms and types of NPs used for different NP-based diagnostics and therapy.
Magnetic nanoparticles (MNPs) are one sub-class of this broad cancer-therapy designed NPs. The first therapeutic applications of magnetic devices to humans can be chased back to the 16th century, when Austrian physician Franz Anton Mesmer (1734-1815) developed his theories about magnetic fluids. He sustained the influence of invisible ‘universal fluids’ on the human body (after the Newtonian ideas of ‘aether’ associated to gravitational forces and tidal cycles), and proposed his theory of ‘animal magnetism’ gaining notoriety across Europe. Since then Mesmerism (a therapeutics based mainly on hypnotism) has triggered a sustained flood of both research and ‘supernatural’ quackery.
Pushed by advances in the synthesis of biocompatible magnetic nanoparticles (MNPs) in a reproducible way, the concept of targeting magnetic nanospheres inside microscopic living organisms regained interest and finally became a reality. Since the size of MNPs is comparable to the DNA or subcellular structures, this field opened the door for cell separation strategies using magnets as external driving forces. Similarly, recent advancements on binding chemistry of biological units onto MNPs surface and the engineering of particle’s surface/shape have opened new exciting possibilities for drug delivery with high selective vectors. Nonetheless, in vivo applications entangle subtle problems related to the response of a living organism to alien objects (i.e., NPs-drug assemblies). For example, even if a perfectly selective drug delivery system could be designed (e.g., by using some monoclonal antibody-loaded particles), any real experiment has to overcome the problem of immunological reactions triggered by the invading NPs within the host, mainly from the reticuloendothelial system (RES).
At present, most applications of MNPs are based on the following physical principles:
a) The application of controlled magnetic field gradients (i.e., a magnetic force) around the desired target location for remotely positioning MNPs in organs or tissues (targeting, magnetic implants, magnetic separation applied to the sequencing of DNA, etc… );
b) The utilization of the magnetic moment of the MNPs as a disturbance of the proton nuclear resonance (e.g., contrast media for Magnetic Resonance Imaging, MRI).
c) The magnetic losses of nanometric particles in colloids for heating purposes (magnetic hyperthermia )
Any of the above applications requires the concourse from many disciplines in order to solve wide-ranging biomedical problems, and there are great efforts being done to approach these problems within multidisciplinary teams. The outcome of these efforts is reflected in comprehensive works and reviews on biomedical applications of MNPs. In this work we propose to review the most recent developments of MNPs applications to cancer therapies, with special emphasis in the physics behind new approaches. In addition to a state-of-the-art landscape of the field, we identify the main obstacles yet to be solved for the next generation of MNPs and their applications.
Magnetic nanoparticles (MNPs) are one sub-class of this broad cancer-therapy designed NPs. The first therapeutic applications of magnetic devices to humans can be chased back to the 16th century, when Austrian physician Franz Anton Mesmer (1734-1815) developed his theories about magnetic fluids. He sustained the influence of invisible ‘universal fluids’ on the human body (after the Newtonian ideas of ‘aether’ associated to gravitational forces and tidal cycles), and proposed his theory of ‘animal magnetism’ gaining notoriety across Europe. Since then Mesmerism (a therapeutics based mainly on hypnotism) has triggered a sustained flood of both research and ‘supernatural’ quackery.
Pushed by advances in the synthesis of biocompatible magnetic nanoparticles (MNPs) in a reproducible way, the concept of targeting magnetic nanospheres inside microscopic living organisms regained interest and finally became a reality. Since the size of MNPs is comparable to the DNA or subcellular structures, this field opened the door for cell separation strategies using magnets as external driving forces. Similarly, recent advancements on binding chemistry of biological units onto MNPs surface and the engineering of particle’s surface/shape have opened new exciting possibilities for drug delivery with high selective vectors. Nonetheless, in vivo applications entangle subtle problems related to the response of a living organism to alien objects (i.e., NPs-drug assemblies). For example, even if a perfectly selective drug delivery system could be designed (e.g., by using some monoclonal antibody-loaded particles), any real experiment has to overcome the problem of immunological reactions triggered by the invading NPs within the host, mainly from the reticuloendothelial system (RES).
At present, most applications of MNPs are based on the following physical principles:
a) The application of controlled magnetic field gradients (i.e., a magnetic force) around the desired target location for remotely positioning MNPs in organs or tissues (targeting, magnetic implants, magnetic separation applied to the sequencing of DNA, etc… );
b) The utilization of the magnetic moment of the MNPs as a disturbance of the proton nuclear resonance (e.g., contrast media for Magnetic Resonance Imaging, MRI).
c) The magnetic losses of nanometric particles in colloids for heating purposes (magnetic hyperthermia )
Any of the above applications requires the concourse from many disciplines in order to solve wide-ranging biomedical problems, and there are great efforts being done to approach these problems within multidisciplinary teams. The outcome of these efforts is reflected in comprehensive works and reviews on biomedical applications of MNPs. In this work we propose to review the most recent developments of MNPs applications to cancer therapies, with special emphasis in the physics behind new approaches. In addition to a state-of-the-art landscape of the field, we identify the main obstacles yet to be solved for the next generation of MNPs and their applications.
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