Nanotechnology and science of nanomaterials provide apt potential in engineering of materials and at present is the enormously growing and developing scientific technology. It is defined as the study of controlling, manipulating and creating systems based on their atomic or molecular specifications. As stated by the US National Science and Technology Council, the essence of nanotechnology is the ability to manipulate matters at atomic, molecular and supra-molecular levels for creation of newer structures and devices. Generally this science deals with structures sized between 1 to 100 nanometer (nm) in at least one dimension and involves in modulation and fabrication of nanomaterials and nanodevices. It has been endured as an area of intense scientific research in various fields like optical, electronic and biomedical fields. Bacterial cells, plant cells and mammalian cells which are more than 100 nm size can easily engulf or internalize the particulates of nano-size like viruses (75-100 nm), proteins (5-50 nm), nucleic acids (2 nm width) and atoms (0.1 nm). If we compare a single human hair diameter (50 μm) to 1 nm nanofibre, hair will be 50,000 times larger than the size of 1 nm. The great visionary late Nobel Physicist Richard P Feynman first designed the idea of molecular manufacturing in 1959. The legendary scientist who first suggested that devices and materials could someday have atomic specifications and that this development path cannot be avoided. For years this science have engaged scientist in exploring the very unique physico-chemical properties of nanoparticles.
Medical Use of Nanopartiches
Nanoparticles for Bioimaging
A number of molecular imaging techniques, such as optical imaging (OI), magnetic resonance imaging (MRI), ultrasound imaging (USI), positron-emission tomography (PET), and others, have been reported for imaging of in vitro and in vivo biological specimens. The current development of luminescent and magnetic nanoparticles advances bioimaging technologies. Two different type of nanoparticles have been widely used for imaging: luminescent nanoprobes for OI and magnetic nanoparticles for MRI. There are also dual-mode nanoparticles for simultaneous imaging by OI and MRI.
In Vitro Diagnostics
Novel sensor concepts based on nanotubes, nanowires, cantilevers, or atomic force microscopy are applied to diagnostic devices/sensors. The aim of these sensors is to improve the sensitivity, reduce production costs, or measure novel analytes (e.g., Alzheimer plaques) that were not detected until recently. For example, Nanomix (Emeryville, California) developed carbon nanotube–based sensors for monitoring the respiratory functions, and Bioforce’s Virichip (Ames, Iowa) uses atomic force microscopy for the detection of whole viruses for early diagnosis of viral infections.Known core materials and corresponding possible ligands used for surface functionalization.
Multifunctional Nanoparticles for Cancer Therapy
Biodegradable chitosan nanoparticles encapsulating quantum dots were prepared by D. K. Chatterjee and Y. Zhang, with suitable surface modification to immobilize both tumor targeting agent and chemokine on their surfaces. The interactions between immune cells and tumor cells were visualized using optical microscope. Use of quantum dots in the treatment of cancer is a great advancement in this area. Quantum dots glow when exposed to UV light. When injected they seep into cancer tumor and the surgeon can see the glowing tumor. Nanotechnology could be very helpful in regenerating the injured nerves. During the last decade, however, developments in the areas of surface microscopy, silicon fabrication, biochemistry, physical chemistry, and computational engineering have converged to provide remarkable capabilities for understanding, fabricating, and manipulating structures at the atomic level. The rapid evolution of this new science and the opportunities for its application demonstrates that nanotechnology will become one of the dominant technologies of the 21st century.
In a recent study, antibody-conjugated magnetic poly-(d, l-lactide-co-glycolide) (PLGA) nanoparticles with doxorubicin (DOX) were synthesized for the simultaneous targeted detection and treatment of breast cancer. DOX and magnetic nanoparticles were incorporated into PLGA nanoparticles, with DOX serving as an anticancer drug and Fe2O3 nanoparticles used as an imaging agent. They also used antibody herceptin 1 for targeting the breast cancer.
The use of magnetic nanoparticles embedded into PLGA nanoparticles for diagnosis and treatment of diseases. PLGA = poly-(d,l-lactide-co-glycolide).
Nanoparticles as Drug Delivery Systems (DDSs)
DDSscan improve several crucial properties of “free” drugs, such as solubility, in vivo stability, pharmacokinetics, and biodistribution, enhancing their efficacy. In this aspect, nanoparticles can be used as a potential DDS owing to their advantageous characteristics, as mentioned previously. As an example of cellular delivery, mixed monolayer protected gold clusters were exploited for in vitro delivery of a hydrophobic fluorophore (BODIPY) (BODIPY are a class of organic fluorescent dyes which have recently become interesting for organic photovoltaics because of their strong tuneable infrared absorption and their high stability); an analog of hydrophobic drugs.
The cationic surface of the nanoparticles facilitated the penetration through cell membrane, and the payload release was triggered by intracellular glutathione (GSH), relying on the ca. 1,000-fold higher intracellular concentration of GSH relative to the extracellular environment. Release of the dye was established by fluorogenesis upon release of the dye from the quenching nanoparticle. The controlled release of the fluorophore was observed in mouse embryonic fibroblast (MEF) cells, containing ca. 50% lower GSH levels than Hep G2; through incubation GSH monoethyl ester (GSH-OEt) is processed to GSH by esterases, transiently increasing intracellular GSH concentrations. Lin et al. have demonstrated that thiols, such as dihydrolipoic acid (DHLA) and dithiothreitol (DTT), can likewise act as stimuli to remove caps of the pores in mesoporous silica nanoparticles and hence release trapped molecules inside the pores. The pores were capped with removable cadmium sulfide (CdS) or ferric oxide (Fe3O4) nanoparticles through disulfide linkers that cleave in a reducing environment.
Release of encapsulated fluorescein isothiocyanate (FITC) from magnetic nanoparticle-capped MCM-41 was observed in cancer cells owing to the presence of significant amounts of intracellular DHLA. pH-responsive nanomateials provide an alternate mechanism for release, relying on the acidic condition inside the tumor and inflamed tissues (pH 6.8) and cellular compartments including endosomes (pH 5.5–6) and lysosomes (pH 4.5–5.0). Toward this end, magnetic nanoparticles (Fe3O4) were covalently functionalized with DOX, an anticancer drug, through an acid-labile hydrazone linker. The carrier was then encapsulated with thermosensitive polymer for temperature-controlled release of the drug. The hybrid system released DOX efficiently in mild acidic buffer solution of pH 5.3. Schoenfisch et al. have likewise shown that nitric oxide (NO) can be efficiently released at acidic pH from gold nanoparticles.
Besides the surface chemistry of nanoparticles, the unique physical properties of nanoparticles have been utilized in the design of DDSs. Ford et al. have designed a water-soluble nanocontainer for NO storage based on electrostatic assembly of DHLA-coated quantum dots and cationic dinitro complexes that uses energy transfer from the core to release NO. In another approach, doping of Ag/Au nanoparticles serves as an antenna to absorb the energy from a laser beam of “biologically friendly” near-infrared (NIR) region, causing local heating and disruption of microcapsules. More recently, Bhatia et al. designed multifunctional super paramagnetic nanoparticles for remote release of bound drugs. The particles transduce external electromagnetic force (EMF) at 350–400 kHz to local heating for breaking hydrogen bonds between DNA chains.
The cationic surface of the nanoparticles facilitated the penetration through cell membrane, and the payload release was triggered by intracellular glutathione (GSH), relying on the ca. 1,000-fold higher intracellular concentration of GSH relative to the extracellular environment. Release of the dye was established by fluorogenesis upon release of the dye from the quenching nanoparticle. The controlled release of the fluorophore was observed in mouse embryonic fibroblast (MEF) cells, containing ca. 50% lower GSH levels than Hep G2; through incubation GSH monoethyl ester (GSH-OEt) is processed to GSH by esterases, transiently increasing intracellular GSH concentrations. Lin et al. have demonstrated that thiols, such as dihydrolipoic acid (DHLA) and dithiothreitol (DTT), can likewise act as stimuli to remove caps of the pores in mesoporous silica nanoparticles and hence release trapped molecules inside the pores. The pores were capped with removable cadmium sulfide (CdS) or ferric oxide (Fe3O4) nanoparticles through disulfide linkers that cleave in a reducing environment.
Release of encapsulated fluorescein isothiocyanate (FITC) from magnetic nanoparticle-capped MCM-41 was observed in cancer cells owing to the presence of significant amounts of intracellular DHLA. pH-responsive nanomateials provide an alternate mechanism for release, relying on the acidic condition inside the tumor and inflamed tissues (pH 6.8) and cellular compartments including endosomes (pH 5.5–6) and lysosomes (pH 4.5–5.0). Toward this end, magnetic nanoparticles (Fe3O4) were covalently functionalized with DOX, an anticancer drug, through an acid-labile hydrazone linker. The carrier was then encapsulated with thermosensitive polymer for temperature-controlled release of the drug. The hybrid system released DOX efficiently in mild acidic buffer solution of pH 5.3. Schoenfisch et al. have likewise shown that nitric oxide (NO) can be efficiently released at acidic pH from gold nanoparticles.
Besides the surface chemistry of nanoparticles, the unique physical properties of nanoparticles have been utilized in the design of DDSs. Ford et al. have designed a water-soluble nanocontainer for NO storage based on electrostatic assembly of DHLA-coated quantum dots and cationic dinitro complexes that uses energy transfer from the core to release NO. In another approach, doping of Ag/Au nanoparticles serves as an antenna to absorb the energy from a laser beam of “biologically friendly” near-infrared (NIR) region, causing local heating and disruption of microcapsules. More recently, Bhatia et al. designed multifunctional super paramagnetic nanoparticles for remote release of bound drugs. The particles transduce external electromagnetic force (EMF) at 350–400 kHz to local heating for breaking hydrogen bonds between DNA chains.
Surgery
At Rice University, a flesh welder is used to fuse two pieces of chicken meat into a single piece. The two pieces of chicken are placed together touching. A greenish liquid containing gold-coated nanoshells is dribbled along the seam. An infrared laser is traced along the seam, causing the two sides to weld together. This could solve the difficulties and blood leaks caused when a surgeon tries to restitch the arteries that have been cut during a kidney or heart transplant. The flesh welder could weld the arteries perfectly.
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