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Recent Advancements of Nanoparticles as a Nanomedicine

Introduction of Nanoparticles:

Nanotechnology is the technology which allows the manipulation, study, control, manufacture of the devices and structures in the size range of nanometer. The nanomaterials such as nanoparticles are very trendy in use due to their remarkable properties and their functions. Their characteristics: customized surface, improved solubility, small size and multi-functionality have paved a way to new medical applications as they form interactions at cellular levels.

Nanotechnology uses the one billionth part of a meter i.e. 10^-9 (smaller than every object of daily life according to Newton’s law and as bigger than an atom described by Quantum physics: ranges b/w 1-100m)for manipulating the matter at the molecular and atomic level. Nanoparticles are used for fabrication of nanostructures as they have different chemical and physical properties which make them prone to be used in industries.

Nanomedicine is a highly interdisciplinary field and helpful for understanding the interaction with the human body.Nanomedicine is a highly interdisciplinary field and helpful for understanding the interaction with the human body.
Fig. 01: Nanomedicine is an interdisciplinary field.

Recent nanotechnology emerged in the 1980s with the experimental advancement of the discovery and use of scanning microscope (1981), fullerenes (1985) respectively, later on, a book was also published (1986) on nanotechnology. In the 2000s, the government raised awareness as well as funds for the development of this technology leading to its application’s success.

In another example of Middle Ages soluble gold was extensively used to cure many heart diseases, tumours, epilepsy, dysentery, venereal diseases, as well as diagnosing syphilis. All the history of ancient times up to Middle Ages related to the use of nanotechnology is shortlisted by Astruc and Daniel. In a book (1618) on Colloidal Gold was also published by a medical doctor named Francisci Antonii.

Types of Nanoparticles:

There are basically four types of nanomaterial:

1, Dendrimers

2. Composites

3. Carbon based materials

4. Metal based materials

Carbon Based Materials

As it is clear from the name that they contain carbon in the form of ellipsoids, tubes or spheres. Ellipsoid or spherical ones are called fullerenes while nanotubes are of cylindrical types. This type has many applications in the field of electronics.

Metal Based Materials

This category comprises of nanogold, metal oxides (titanium oxide), quantum dots and nano-silver. Quantum dots among them are closely packed crystals acting as a semiconductor containing numerous nanoparticles and atoms, by changing their size we can change the optical properties of quantum dots.

Dendrimers

This type is a 3D polymer, outer part contains branched units making surface chains which are responsible for various chemical reactions such as catalysis. The inner part has cavities for other molecules to fit in: an important use for drug delivery.

Composites

This type composed of combination of nanoparticles with either nano-sized particles or some bulk materials. These are used in packaging materials to enhance thermal, mechanical, flame retardant and barrier properties.

Nanozymes

Scientists have developed new artificial enzymes (alternative to naturally existing enzymes) which are very stable, cost-effective and have many applications. The materials were explored to mimic natural enzymes contained porphyrin rings, polymers, cyclodextrins, biomolecules and nanoparticles. Amongst all nanoparticles are the most efficient in mimicking natural enzymes, hence named as nanozymes which have numerous uses in immunoassays, bio-sensing, pollutant removal and stem cell growth.

Magnetic nanoparticles:

MNPs are used for MRI i.e. magnetic resonance imaging. These nanoparticles are non-invasive and have specific physicochemical and surface properties (adherence, coating, size, ligand binding molecular functioning) due to which they are used in drug delivery, cellular specific targeting by modifying their properties.

Different types of nanoparticle which can be used for useful purposes. Different types of nanoparticle which can be used for useful purposes.
Fig. 02: Types of Nanoparticles

Nanomedicine and Diagnostics:

nanoparticles have three-dimensional shape and they have internal compartments for other molecules to fit it in, so various drugs can be placed in them and nanoparticles are bombarded to the targeted sites or the specific sites to be treated. The properties of the nanoparticles’ surface, their physicochemical properties, release properties, delivery properties, stability, pH, can be modified, their toxicity could be reduced by various methods. Targeted drug delivery is significant in case of chemotherapies, to remove tumors. Oral and other drugs could take from hours to more long to reach a target or defective area, or may not even reach a target area. Using drugs through drug delivery carriers such as nanomaterial is hence useful. Two systems are used for carrying the drugs; depends on the preparation of nanomaterial produced for better delivery and release properties of drugs.

1: Nanocapsules, they are vascular bodies containing cavities in which the drugs are confined, around which a membrane of polymers covers.

2 Nanospheres containing macromolecular substances, are colloidal, solid particles (10nm-100nm). The drug is first dissolved and then adsorbed or attached or filled in the matrix of nanoparticles.

Difference between nanosphere and nanocapsule.Difference between nanosphere and nanocapsule.
Fig. 03: Nanosphere and Nanocapsule

Incorporation of drugs is achieved by either direct incorporation (polymerization) or by adsorbing the drug in nanoparticles in anticancer drugs, efficacy of drug release, adsorption, desorption, target selectivity and incorporation is examined using isotherms and kinetics as well using models of monoclonal antibodies binding to homing device. Target specificity is checked by labelling nanoparticles with radioactive material emitting gamma particles.

Nanomedicines have two Advantages in diagnostics

A disease can be diagnosed at its early stage and the patient thus may face less damage. As early diagnosis will lead to early treatment.

1. Within a single test, a disease can be diagnosed, leads the doctor to start a proper treatment rather than more or follow-up visits.

2. Nanoparticles carrying the drugs are coated with specific ligands which attach with their compatible(target) surfaces and release the drug to kill those targets. Many researchers have been working on such particles which make the detection of diseases earlier.

Mechanism

Nanoparticles are coated with a specific ligand such as folic acid, lectins, antigens, antibodies, carbohydrates etc. to detect the presence of certain pathogens or cancerous cells. Then they are attached with boilable such as fluorescent material, chemiluminescent or bioluminescent. For example, when the nanomedicine reaches the target cells say a tumor, the nanoparticles start releasing some biomarkers which are peptide molecules. These biomarkers are quantified. In both cases of luminescent material and biomarker quantification, more light and higher concentration relate high pathogenicity, hence, even at early stages of cancer biomarkers can be identified.

Basically, four steps could be followed in a diagnostic nano-medicine:

1. Attachment of therapeutic/ diagnostic agent

2. Targeting

3. Controlled release

4, Imaging

Different steps which are involved in diagnosis via nanomedicine. Different steps which are involved in diagnosis via nanomedicine.
Fig. 04: Diagnostic steps for nanomedicine

Nanofalairs

 These Nanomedicines are mostly used for detecting cancer and other infectious diseases by testing the bloodstream, as these nanoflares have the ability to bind to specific targets present on the surface of cancer cells and produce light which is an indication of their attachment to target cells.

Microvesicles

Magnetic nanoparticles (NMR) have been used for the early detection of brain cancer. In the diagnosis of brain cancer, NMR attach to the microvesicles present in bloodstream (originated from the brain), making clusters with each other. The magnetic signals produced are then detected by magnetometer.

Biosensors and Nanofibres

Gold and carbon -nanotubes have been used as a biosensor which detects proteins expressed in oral cancer, providing the results within an hour. Moreover, some nano-particles have been made by researches with the ability to attack freely moving cancerous cells. These nanofibers are coated with the antibodies, which bind and trap the cancer cells for further analysis.

Silver Nanorods

As infectious agents like bacteria, viruses and other microscopic organisms are also present in blood samples, they can also be detected using silver nanorods taking less than one hour. The signals produced by these nanoparticles are detected and quantified by Raman spectroscopy signals.

Siver Nanorods for the diagnosis of different bacterial infections.Siver Nanorods for the diagnosis of different bacterial infections.
Fig.05: Silver Nanorods

Verigene Systems

Researchers have developed nano-spheres, which are gold nanoparticles having the ability to determine four types of nucleic acids. According to the suspected specimen, antibodies are attached to the gold- nanoparticles for the diagnosis of the flu virus. After attachment with the targets, light illuminates the sample which contains nanoparticles and viruses. The amount of reflected light increases when nanoparticles surround the viruses.

Similarly, other nanoparticles also can diagnose nucleic acids, proteins thus, they can detect specimens in the bloodstream because of their T2-biosystems.

Clumping Nanoparticles

Utilizing the ability of some nanoparticles to clump together with proteins, another diagnostic test can be performed by using them. The method is in-expensive and easy to perform as the proteins give blue colour in the presence of an infectious protein. If proteins are not present the solution will be red.

Quantum Dots (QDots)

Qdots along with fluorescent material can also be used for diagnostic purposes to find tumors and cancers in the samples from patients. In vivo (limited) and in vitro tests have been performed by these nanoparticles, data is provided by a site named Invitrogen.

Iron Oxide Nanoparticles

Iron oxide nanoparticles Could also be used to get MRI images of cancer/tumors. The nanoparticles are coated with a peptide which will bind to a tumor/cancerous cell. When the nanoparticles get attached to the tumor, the magnetic property of iron oxide is used to produce images by Magnetic Resonance imaging technique/scan.

Limitations of Nanoparticles

There are many advantages of using nanoparticles or nanomedicine for diagnostic purposes, but still, they have some limitations such as the toxicity of the material that quantum dots are made from is one of the reasons restricting the use of quantum dots in human patients. However, work is being done with quantum dots composed of silicon which is believed to be less toxic than the cadmium contained in many quantum dots. Biocompatibility is another limitation. There are some diseases such as Alzheimer, haemophilia, down’s syndrome and many other diseases which are related to human pedigree are still not diagnosed using nano-medicine.

Future Prospects of Nanoparticles

As the distribution of the drug is difficult, since the nanoparticles have to face many biological barriers inside the body, considering the surface properties and their retention in the bloodstream, drug delivery could be improved for better action. Optimum sized nanoparticles have been designed, the smaller the size the greater would be the surface area and its circulation in the blood also increases. Using the specific pathological physiology of tumor cells, nanoparticles could also carry loaded drug delivery which is enhanced by increased permeability. Using active target approached is better in providing specificity than passive drug delivery. Drug resistance is also reduced using nanoparticles, which can be further improved by working on their retention time in the bloodstream. Now a days multiplex nanoparticles are also being experimented to perform multifunction in the next generation to treat cancers.

Nano-particles have been widely used as they can overcome different difficulties emerging in therapeutic delivery (tumor site) because of their passive and active mechanism. Exclusive properties of nano-particles such as large surface area, small size, encapsulating ability for drugs, extended circulation time, easy passing from cell membranes, target specificity have made them trendy to be in use for tumor treatment. With more advancements: use of polymeric nanoparticles, dendrimers, polyplexes and micelles, they could treat and detect the tumors in a better way soon.

Conclusion

By improving the surface properties of nanoparticles, their efficacy can be improved. Many experiments have been done and being done in order to produce multifunctional nanoparticles for various disorders, mainly cancer which requires strictly targeted drug delivery. Moreover, in many other examples in clinical and pharmaceuticals fields, use nanoparticles which are very trendy and can be used for various therapeutic purposes.

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