Nanomedicine

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Nanomedicine is the medical application of nanotechnology. [1] Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials (materials whose structure is on the scale of nanometers, i.e. billionths of a meter). [2] [3]

Contents

Functionalities can be added to nanomaterials by interfacing them with biological molecules or structures. The size of nanomaterials is similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications. Thus far, the integration of nanomaterials with biology has led to the development of diagnostic devices, contrast agents, analytical tools, physical therapy applications, and drug delivery vehicles.

Nanomedicine seeks to deliver a valuable set of research tools and clinically useful devices in the near future. [4] [5] The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that may include advanced drug delivery systems, new therapies, and in vivo imaging. [6] Nanomedicine research is receiving funding from the US National Institutes of Health Common Fund program, supporting four nanomedicine development centers. [7]

Nanomedicine sales reached $16 billion in 2015, with a minimum of $3.8 billion in nanotechnology R&D being invested every year. Global funding for emerging nanotechnology increased by 45% per year in recent years, with product sales exceeding $1 trillion in 2013. [8] As the nanomedicine industry continues to grow, it is expected to have a significant impact on the economy.

Drug delivery

Nanoparticles biomolecule interaction.svg
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Nanoparticles (top), liposomes (middle), and dendrimers (bottom) are some nanomaterials being investigated for use in nanomedicine.

Nanotechnology has provided the possibility of delivering drugs to specific cells using the nanoparticles. [9] [10] The overall drug consumption and side-effects may be lowered significantly by depositing the active pharmaceutical agent in the morbid region only and in no higher dose than needed. Targeted drug delivery is intended to reduce the side effects of drugs with concomitant decreases in consumption and treatment expenses. Additionally, targeted drug delivery reduces the side effect possessed by crude drug via minimizing undesired exposure to the healthy cells. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. This can potentially be achieved by molecular targeting by nanoengineered devices. [11] [12] A benefit of using nanoscale for medical technologies is that smaller devices are less invasive and can possibly be implanted inside the body, plus biochemical reaction times are much shorter. These devices are faster and more sensitive than typical drug delivery. [13] The efficacy of drug delivery through nanomedicine is largely based upon: a) efficient encapsulation of the drugs, b) successful delivery of drug to the targeted region of the body, and c) successful release of the drug. [14] Several nano-delivery drugs were on the market by 2019. [15]

Drug delivery systems, lipid- [16] or polymer-based nanoparticles, can be designed to improve the pharmacokinetics and biodistribution of the drug. [17] [18] [19] However, the pharmacokinetics and pharmacodynamics of nanomedicine is highly variable among different patients. [20] When designed to avoid the body's defence mechanisms, [21] nanoparticles have beneficial properties that can be used to improve drug delivery. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell membranes and into cell cytoplasm. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility. [22] Drug delivery systems may also be able to prevent tissue damage through regulated drug release; reduce drug clearance rates; or lower the volume of distribution and reduce the effect on non-target tissue. However, the biodistribution of these nanoparticles is still imperfect due to the complex host's reactions to nano- and microsized materials [21] and the difficulty in targeting specific organs in the body. Nevertheless, a lot of work is still ongoing to optimize and better understand the potential and limitations of nanoparticulate systems. While advancement of research proves that targeting and distribution can be augmented by nanoparticles, the dangers of nanotoxicity become an important next step in further understanding of their medical uses. [23] The toxicity of nanoparticles varies, depending on size, shape, and material. These factors also affect the build-up and organ damage that may occur. Nanoparticles are made to be long-lasting, but this causes them to be trapped within organs, specifically the liver and spleen, as they cannot be broken down or excreted. This build-up of non-biodegradable material has been observed to cause organ damage and inflammation in mice. [24] Magnetic targeted delivery of magnetic nanoparticles to the tumor site under the influence of inhomogeneous stationary magnetic fields may lead to enhanced tumor growth. In order to circumvent the pro-tumorigenic effects, alternating electromagnetic fields should be used. [25]

Nanoparticles are under research for their potential to decrease antibiotic resistance or for various antimicrobial uses. [26] [27] [28] [29] Nanoparticles might also be used to circumvent multidrug resistance (MDR) mechanisms. [9]

Systems under research

Advances in lipid nanotechnology were instrumental in engineering medical nanodevices and novel drug delivery systems, as well as in developing sensing applications. [30] Another system for microRNA delivery under preliminary research is nanoparticles formed by the self-assembly of two different microRNAs deregulated in cancer. [31] One potential application is based on small electromechanical systems, such as nanoelectromechanical systems being investigated for the active release of drugs and sensors for possible cancer treatment with iron nanoparticles or gold shells. [32] Another system of drug delivery involving nanoparticles is the use of aquasomes, self-assembled nanoparticles with a nanocrystalline center, a coating made of a polyhydroxyl oligomer, covered in the desired drug, which protects it from dehydration and conformational change. [33] The potential prospects of the unique structure and function of prefoldin in nanomedicine are being explored. [34]

Applications

Some nanotechnology-based drugs that are commercially available or in human clinical trials include:

Imaging

In vivo imaging is another area where tools and devices are being developed. [41] Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. In cardiovascular imaging, nanoparticles have potential to aid visualization of blood pooling, ischemia, angiogenesis, atherosclerosis, and focal areas where inflammation is present. [41]

The small size of nanoparticles endows them with properties that can be very useful in oncology, particularly in imaging. [9] Quantum dots (nanoparticles with quantum confinement properties, such as size-tunable light emission), when used in conjunction with MRI (magnetic resonance imaging), can produce exceptional images of tumor sites. Nanoparticles of cadmium selenide (quantum dots) glow when exposed to ultraviolet light. When injected, they seep into cancer tumors. The surgeon can see the glowing tumor, and use it as a guide for more accurate tumor removal. These nanoparticles are much brighter than organic dyes and only need one light source for excitation. This means that the use of fluorescent quantum dots could produce a higher contrast image and at a lower cost than today's organic dyes used as contrast media. The downside, however, is that quantum dots are usually made of quite toxic elements, but this concern may be addressed by use of fluorescent dopants. [42]

Tracking movement can help determine how well drugs are being distributed or how substances are metabolized. It is difficult to track a small group of cells throughout the body, so scientists used to dye the cells. These dyes needed to be excited by light of a certain wavelength in order for them to light up. While different color dyes absorb different frequencies of light, there was a need for as many light sources as cells. A way around this problem is with luminescent tags. These tags are quantum dots attached to proteins that penetrate cell membranes. [42] The dots can be random in size, can be made of bio-inert material, and they demonstrate the nanoscale property that color is size-dependent. As a result, sizes are selected so that the frequency of light used to make a group of quantum dots fluoresce is an even multiple of the frequency required to make another group incandesce. Then both groups can be lit with a single light source. They have also found a way to insert nanoparticles [43] into the affected parts of the body so that those parts of the body will glow showing the tumor growth or shrinkage or also organ trouble. [44]

Sensing

Nanotechnology-on-a-chip is one more dimension of lab-on-a-chip technology. Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms. In particular silica nanoparticles are inert from the photophysical point of view and might accumulate a large number of dye(s) within the nanoparticle shell. [45] Gold nanoparticles tagged with short segments of DNA can be used for detection of genetic sequence in a sample. Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots into polymeric microbeads. Nanopore technology for analysis of nucleic acids converts strings of nucleotides directly into electronic signatures.[ citation needed ]

Sensor test chips containing thousands of nanowires, able to detect proteins and other biomarkers left behind by cancer cells, could enable the detection and diagnosis of cancer in the early stages from a few drops of a patient's blood. [46] Nanotechnology is helping to advance the use of arthroscopes, which are pencil-sized devices that are used in surgeries with lights and cameras so surgeons can do the surgeries with smaller incisions. The smaller the incisions the faster the healing time which is better for the patients. It is also helping to find a way to make an arthroscope smaller than a strand of hair. [47]

Research on nanoelectronics-based cancer diagnostics could lead to tests that can be done in pharmacies. The results promise to be highly accurate and the product promises to be inexpensive. They could take a very small amount of blood and detect cancer anywhere in the body in about five minutes, with a sensitivity that is a thousand times better a conventional laboratory test. These devices are built with nanowires to detect cancer proteins; each nanowire detector is primed to be sensitive to a different cancer marker. [32] The biggest advantage of the nanowire detectors is that they could test for anywhere from ten to one hundred similar medical conditions without adding cost to the testing device. [48] Nanotechnology has also helped to personalize oncology for the detection, diagnosis, and treatment of cancer. It is now able to be tailored to each individual's tumor for better performance. They have found ways that they will be able to target a specific part of the body that is being affected by cancer. [49]

Sepsis treatment

In contrast to dialysis, which works on the principle of the size related diffusion of solutes and ultrafiltration of fluid across a semi-permeable membrane, the purification with nanoparticles allows specific targeting of substances. [50] Additionally larger compounds which are commonly not dialyzable can be removed. [51]

The purification process is based on functionalized iron oxide or carbon coated metal nanoparticles with ferromagnetic or superparamagnetic properties. [52] Binding agents such as proteins, [50] antibiotics, [53] or synthetic ligands [54] are covalently linked to the particle surface. These binding agents are able to interact with target species forming an agglomerate. Applying an external magnetic field gradient allows exerting a force on the nanoparticles. Hence the particles can be separated from the bulk fluid, thereby cleaning it from the contaminants. [55] [56]

The small size (< 100 nm) and large surface area of functionalized nanomagnets leads to advantageous properties compared to hemoperfusion, which is a clinically used technique for the purification of blood and is based on surface adsorption. These advantages are high loading and accessible for binding agents, high selectivity towards the target compound, fast diffusion, small hydrodynamic resistance, and low dosage. [57]

Tissue engineering

Nanotechnology may be used as part of tissue engineering to help reproduce or repair or reshape damaged tissue using suitable nanomaterial-based scaffolds and growth factors. Tissue engineering if successful may replace conventional treatments like organ transplants or artificial implants. Nanoparticles such as graphene, carbon nanotubes, molybdenum disulfide and tungsten disulfide are being used as reinforcing agents to fabricate mechanically strong biodegradable polymeric nanocomposites for bone tissue engineering applications. The addition of these nanoparticles in the polymer matrix at low concentrations (~0.2 weight %) leads to significant improvements in the compressive and flexural mechanical properties of polymeric nanocomposites. [58] [59] Potentially, these nanocomposites may be used as a novel, mechanically strong, light weight composite as bone implants.[ citation needed ]

For example, a flesh welder was demonstrated to fuse two pieces of chicken meat into a single piece using a suspension of gold-coated nanoshells activated by an infrared laser. This could be used to weld arteries during surgery. [60] Another example is nanonephrology, the use of nanomedicine on the kidney.

Vaccine development

Today, a significant part of vaccines against viral diseases are created using nanotechnology. Solid lipid nanoparticles are a novel delivery system for some vaccines against SARS-CoV-2 (the virus that causes COVID-19). To improve the immune response to targeted vaccine antigens, nanosized adjuvants have been widely used in recent decades. Inorganic nanoparticles of alum, [61] silica and clay, as well as  organic nanoparticles based on polymers and lipids, are very popular adjuvants within modern vaccine formulations. [62] Nanoparticles of natural polymers such as chitosan are useful for vaccine development due to their biocompatibility and biodegradability. [63] Ceria nanoparticles appear very promising for both enhancing vaccine response and mitigating inflammation, since their adjuvanticity can be adjusted by changing nanoparticle parameters (size, crystallinity, surface state, stoichiometry, etc.). [64]

Medical devices

Neuro-electronic interfacing is a visionary goal dealing with the construction of nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the building of a molecular structure that will permit control and detection of nerve impulses by an external computer. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, magnetic, or biological electrical sources, while a non-refuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained. A nanoscale enzymatic biofuel cell for self-powered nanodevices have been developed that uses glucose from biofluids including human blood and watermelons. [65] One limitation to this innovation is the fact that electrical interference or leakage or overheating from power consumption is possible. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system. The structures that will provide the interface must also be compatible with the body's immune system. [66]

Cell repair machines

Molecular nanotechnology is a speculative subfield of nanotechnology regarding the possibility of engineering molecular assemblers, machines which could re-order matter at a molecular or atomic scale.[ citation needed ] Nanomedicine would make use of these nanorobots, introduced into the body, to repair or detect damages and infections. Molecular nanotechnology is highly theoretical, seeking to anticipate what inventions nanotechnology might yield and to propose an agenda for future inquiry. The proposed elements of molecular nanotechnology, such as molecular assemblers and nanorobots are far beyond current capabilities. [1] [66] [67] Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler, one of the founders of nanotechnology, postulated cell repair machines, including ones operating within cells and utilizing as yet hypothetical molecular machines, in his 1986 book Engines of Creation , with the first technical discussion of medical nanorobots by Robert Freitas appearing in 1999. [1] Raymond Kurzweil, a futurist and transhumanist, stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030. [68] According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him (c. 1959) the idea of a medical use for Feynman's theoretical micromachines (see nanotechnology). Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would, in theory, be possible to (as Feynman put it) "swallow the doctor". The idea was incorporated into Feynman's 1959 essay There's Plenty of Room at the Bottom. [69]

See also

Related Research Articles

<span class="mw-page-title-main">Nanotechnology</span> Field of science involving control of matter on atomic and (supra)molecular scales

Nanotechnology was defined by the National Nanotechnology Initiative as the manipulation of matter with at least one dimension sized from 1 to 100 nanometers (nm). At this scale, commonly known as the nanoscale, surface area and quantum mechanical effects become important in describing properties of matter. The definition of nanotechnology is inclusive of all types of research and technologies that deal with these special properties. It is therefore common to see the plural form "nanotechnologies" as well as "nanoscale technologies" to refer to the broad range of research and applications whose common trait is size. An earlier description of nanotechnology referred to the particular technological goal of precisely manipulating atoms and molecules for fabrication of macroscale products, also now referred to as molecular nanotechnology.

Nanosensors are nanoscale devices that measure physical quantities and convert these to signals that can be detected and analyzed. There are several ways proposed today to make nanosensors; these include top-down lithography, bottom-up assembly, and molecular self-assembly. There are different types of nanosensors in the market and in development for various applications, most notably in defense, environmental, and healthcare industries. These sensors share the same basic workflow: a selective binding of an analyte, signal generation from the interaction of the nanosensor with the bio-element, and processing of the signal into useful metrics.

<span class="mw-page-title-main">Nanorobotics</span> Emerging technology field

Nanoid robotics, or for short, nanorobotics or nanobotics, is an emerging technology field creating machines or robots, which are called nanorobots or simply nanobots, whose components are at or near the scale of a nanometer. More specifically, nanorobotics refers to the nanotechnology engineering discipline of designing and building nanorobots with devices ranging in size from 0.1 to 10 micrometres and constructed of nanoscale or molecular components. The terms nanobot, nanoid, nanite, nanomachine and nanomite have also been used to describe such devices currently under research and development.

<span class="mw-page-title-main">Nanobiotechnology</span> Intersection of nanotechnology and biology

Nanobiotechnology, bionanotechnology, and nanobiology are terms that refer to the intersection of nanotechnology and biology. Given that the subject is one that has only emerged very recently, bionanotechnology and nanobiotechnology serve as blanket terms for various related technologies.

<span class="mw-page-title-main">Nanochemistry</span> Combination of chemistry and nanoscience

Nanochemistry is an emerging sub-discipline of the chemical and material sciences that deals with the development of new methods for creating nanoscale materials. The term "nanochemistry" was first used by Ozin in 1992 as 'the uses of chemical synthesis to reproducibly afford nanomaterials from the atom "up", contrary to the nanoengineering and nanophysics approach that operates from the bulk "down"'. Nanochemistry focuses on solid-state chemistry that emphasizes synthesis of building blocks that are dependent on size, surface, shape, and defect properties, rather than the actual production of matter. Atomic and molecular properties mainly deal with the degrees of freedom of atoms in the periodic table. However, nanochemistry introduced other degrees of freedom that controls material's behaviors by transformation into solutions. Nanoscale objects exhibit novel material properties, largely as a consequence of their finite small size. Several chemical modifications on nanometer-scaled structures approve size dependent effects.

<span class="mw-page-title-main">Drug delivery</span> Methods for delivering drugs to target sites

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.

Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticle-mediated drug delivery in order to combat the downfalls of conventional drug delivery. These nanoparticles would be loaded with drugs and targeted to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The conventional drug delivery system is the absorption of the drug across a biological membrane, whereas the targeted release system releases the drug in a dosage form. The advantages to the targeted release system is the reduction in the frequency of the dosages taken by the patient, having a more uniform effect of the drug, reduction of drug side-effects, and reduced fluctuation in circulating drug levels. The disadvantage of the system is high cost, which makes productivity more difficult, and the reduced ability to adjust the dosages.

The impact of nanotechnology extends from its medical, ethical, mental, legal and environmental applications, to fields such as engineering, biology, chemistry, computing, materials science, and communications.

Photothermal therapy (PTT) refers to efforts to use electromagnetic radiation for the treatment of various medical conditions, including cancer. This approach is an extension of photodynamic therapy, in which a photosensitizer is excited with specific band light. This activation brings the sensitizer to an excited state where it then releases vibrational energy (heat), which is what kills the targeted cells.

The applications of nanotechnology, commonly incorporate industrial, medicinal, and energy uses. These include more durable construction materials, therapeutic drug delivery, and higher density hydrogen fuel cells that are environmentally friendly. Being that nanoparticles and nanodevices are highly versatile through modification of their physiochemical properties, they have found uses in nanoscale electronics, cancer treatments, vaccines, hydrogen fuel cells, and nanographene batteries.

<span class="mw-page-title-main">Nanocarrier</span>

A nanocarrier is nanomaterial being used as a transport module for another substance, such as a drug. Commonly used nanocarriers include micelles, polymers, carbon-based materials, liposomes and other substances. Nanocarriers are currently being studied for their use in drug delivery and their unique characteristics demonstrate potential use in chemotherapy. This class of materials was first reported by a team of researchers of University of Évora, Alentejo in early 1960's, and grew exponentially in relevance since then.

<span class="mw-page-title-main">Gold nanoparticles in chemotherapy</span> Drug delivery technique using gold nanoparticles as vectors

Gold nanoparticles in chemotherapy and radiotherapy is the use of colloidal gold in therapeutic treatments, often for cancer or arthritis. Gold nanoparticle technology shows promise in the advancement of cancer treatments. Some of the properties that gold nanoparticles possess, such as small size, non-toxicity and non-immunogenicity make these molecules useful candidates for targeted drug delivery systems. With tumor-targeting delivery vectors becoming smaller, the ability to by-pass the natural barriers and obstacles of the body becomes more probable. To increase specificity and likelihood of drug delivery, tumor specific ligands may be grafted onto the particles along with the chemotherapeutic drug molecules, to allow these molecules to circulate throughout the tumor without being redistributed into the body.

Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery and controlled release of therapeutic agents. The modern form of a drug delivery system should minimize side-effects and reduce both dosage and dosage frequency. Recently, nanoparticles have aroused attention due to their potential application for effective drug delivery.

Hamid Ghandehari is an Iranian-American drug delivery research scientist, and a professor in the Departments of Pharmaceutics and Pharmaceutical Chemistry and Biomedical Engineering at the University of Utah. His research is focused in recombinant polymers for drug and gene delivery, nanotoxicology of dendritic and inorganic constructs, water-soluble polymers for targeted delivery and poly(amidoamine) dendrimers for oral delivery.

<span class="mw-page-title-main">Polystyrene (drug delivery)</span> Polystyrene in drug delivery

Polystyrene is a synthetic hydrocarbon polymer that is widely adaptive and can be used for a variety of purposes in drug delivery. These methods include polystyrene microspheres, nanoparticles, and solid foams. In the biomedical engineering field, these methods assist researchers in drug delivery, diagnostics, and imaging strategies.

<span class="mw-page-title-main">Reduction-sensitive nanoparticles</span> Drug delivery method

Reduction-sensitive nanoparticles (RSNP) consist of nanocarriers that are chemically responsive to reduction. Drug delivery systems using RSNP can be loaded with different drugs that are designed to be released within a concentrated reducing environment, such as the tumor-targeted microenvironment. Reduction-Sensitive Nanoparticles provide an efficient method of targeted drug delivery for the improved controlled release of medication within localized areas of the body.

Protein nanotechnology is a burgeoning field of research that integrates the diverse physicochemical properties of proteins with nanoscale technology. This field assimilated into pharmaceutical research to give rise to a new classification of nanoparticles termed protein nanoparticles (PNPs). PNPs garnered significant interest due to their favorable pharmacokinetic properties such as high biocompatibility, biodegradability, and low toxicity Together, these characteristics have the potential to overcome the challenges encountered with synthetic NPs drug delivery strategies. These existing challenges including low bioavailability, a slow excretion rate, high toxicity, and a costly manufacturing process, will open the door to considerable therapeutic advancements within oncology, theranostics, and clinical translational research.

pH-responsive tumor-targeted drug delivery is a specialized form of targeted drug delivery that utilizes nanoparticles to deliver therapeutic drugs directly to cancerous tumor tissue while minimizing its interaction with healthy tissue. Scientists have used drug delivery as a way to modify the pharmacokinetics and targeted action of a drug by combining it with various excipients, drug carriers, and medical devices. These drug delivery systems have been created to react to the pH environment of diseased or cancerous tissues, triggering structural and chemical changes within the drug delivery system. This form of targeted drug delivery is to localize drug delivery, prolongs the drug's effect, and protect the drug from being broken down or eliminated by the body before it reaches the tumor.

Nanomaterials have gained significant attention in the field of cancer research and treatment due to their unique properties and potential applications. These materials, typically on the nanoscale, offer several advantages in the fight against cancer.

Moein Moghimi is a British professor and researcher in the fields of nanomedicine, drug delivery and biomaterials. He is currently the professor of Pharmaceutics and Nanomedicine at the School of Pharmacy and the Translational and Clinical Research Institute at Newcastle University. He is also an adjoint professor at the Skaggs School of Pharmacy, University of Colorado Denver.

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