Nanorobots in cancer treatment pdf
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This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Nanoparticles are rapidly being developed and trialed to nanorobots in cancer treatment pdf several limitations of traditional drug delivery systems and are coming up as a distinct therapeutics for cancer treatment.
Conventional chemotherapeutics possess some serious side effects including damage of the immune system and other organs with rapidly proliferating cells due to nonspecific targeting, lack of solubility, and nanorobots in cancer treatment pdf to enter the core of the tumors resulting in impaired treatment with reduced dose and with low survival rate.
Nanotechnology has provided the opportunity to get direct access of the cancerous cells selectively with increased drug localization and cellular uptake. Nanoparticles can be programmed for recognizing the cancerous cells and giving selective and accurate drug delivery avoiding nanorobots in cancer treatment pdf with the healthy cells. This review focuses on cell recognizing ability of nanoparticles by various strategies having unique identifying properties that distinguish them from previous anticancer therapies.
It also discusses specific nanorobots in cancer treatment pdf delivery by nanoparticles inside the cells illustrating many successful researches and how nanoparticles remove the side effects of conventional therapies with tailored cancer treatment. It is one of the major health concerns of the 21st century which does not have any boundary and can affect any organ of people from any place [ 1 ].
Cancer, the uncontrolled proliferation of cells where apoptosis is greatly disappeared, requires very complex process of treatment. Because of complexity in genetic and phenotypic levels, it shows clinical diversity and therapeutic resistance. A variety of approaches are being practiced for the treatment of cancer each of which has some significant limitations and side effects [ 2 ].
Cancer treatment includes surgical removal, chemotherapy, radiation, and hormone therapy. Chemotherapy, a very common treatment, delivers anticancer drugs systemically to patients forquenching the uncontrolled proliferation of cancerous cells [ 3 ].
Unfortunately, due to nonspecific targeting by anticancer agents, many side effects occur and poor drug delivery of those agents cannot bring out the desired outcome in most of the cases. Cancer drug development involves a very complex procedure which is associated with advanced polymer chemistry and electronic engineering. The main challenge of cancer therapeutics is to differentiate the cancerous cells and the normal body cells. That is why the main objective becomes engineering the drug in such a way as it can identify the cancer cells to diminish their growth and proliferation.
Conventional chemotherapy fails to target the cancerous cells selectively without interacting with the normal body cells. Thus they cause serious side effects including organ damage resulting in impaired treatment with lower dose and ultimately low survival rates [ 4 ]. Nanotechnology is the science that usually deals with the size range from a few nanometers nm to several hundred nm, depending on their intended use [ 5 ].
It has been the area of interest over the last decade for developing precise drug delivery systems as it offers numerous benefits to overcome the limitations of conventional formulations [ 67 ].
It is very promising both in cancer diagnosis and treatment since it can enter the tissues at molecular level. Cancer nanotechnology is being enthusiastically evaluated and implemented in cancer treatment indicating a major advance in detection, diagnosis, and treatment of the disease. Various researches are being carried out in order to discover more accurate nanotechnology based cancer treatment minimizing the side effects of the conventional ones [ 5 ].
Nanoparticles are now being designed to assist therapeutic agents to pass through biologic barriers, to mediate molecular interactions, and to identify molecular changes. They have larger surface area with modifiable optical, electronic, magnetic, and biologic properties compared to macroparticles. Current nanotechnology based drug delivery systems for cancer treatment, which are already marketed and under research and evaluation, include liposomes, polymeric micelles, dendrimers, nanospheres, nanocapsules, and nanotubes [ 89 ].
Nanotechnology based formulations that have already been marketed are DOXIL liposomal doxorubicin and Abraxane albumin bound paclitaxel [ 10 ]. Conventional chemotherapeutic agents work by destroying rapidly dividing cells, which is the main property of neoplastic cells.
This is why chemotherapy also damages normal healthy cells that divide rapidly such as cells in the bone marrow, macrophages, digestive tract, and hair follicles [ 2 ]. The main drawback of conventional chemotherapy is that it cannot give selective action only to the cancerous cells. This results in common side effects of most chemotherapeutic agents which include myelosuppression decreased production of white blood nanorobots in cancer treatment pdf causing immunosuppressionmucositis inflammation of the lining of the digestive tractalopecia hair lossorgan dysfunction, and even anemia or thrombocytopenia.
These side effects sometimes impose dose reduction, treatment delay, or discontinuance of the given therapy [ 1112 ]. In case of solid tumors cell division may be effectively ceased near the center, making chemotherapeutic agents insensitive to chemotherapy. Furthermore, chemotherapeutic agents often cannot penetrate and reach the core of solid tumors, failing to kill the cancerous cells [ 13 ].
Traditional chemotherapeutic agents often get washed out from the circulation being engulfed by macrophages. Thus they remain in the circulation for a very short time and cannot interact with the cancerous cells nanorobots in cancer treatment pdf the chemotherapy completely ineffective. The poor solubility of the drugs is also a major problem in conventional chemotherapy making them unable to penetrate the biological membranes [ 4 ].
Another problem is associated with P-glycoprotein, a multidrug resistance protein that is overexpressed on the surface of the cancerous cells, which prevents drug accumulation inside the tumor, acting as the efflux pump, and often mediates the development of resistance to anticancer drugs.
Thus the administered drugs remain unsuccessful nanorobots in cancer treatment pdf cannot bring the desired output [ 14 — 17 ]. Nanotechnology has nanorobots in cancer treatment pdf a great revolution in selective cancer targeting. Nanoparticles can be designed through various modifications such as changing their size, shape, chemical and physical properties, and so forth, to program them for targeting the desired cells.
They can target the neoplastic cells either through active or passive targeting. In case of active targeting, nanoparticles containing the chemotherapeutic agents are designed in such a way as they directly interact with the defected cells. Active targeting is based on molecular recognition. Hence, the surface of the nanoparticles is modified to target the cancerous cells. Usually, targeting agents are attached with the surface of nanoparticles for molecular recognition.
Designed nanoparticles target the cancerous cells either by ligand-receptor interaction or antibody-antigen recognition [ 18 — 20 ]. Nanotechnology based targeted delivery system has three main components: A variety of substances are used to construct a nanoparticle.
Commonly used materials include ceramic, polymers, lipids, and metals [ 21 nanorobots in cancer treatment pdf. Natural and synthetic polymers and lipids are typically used as drug delivery vectors [ 22 — 24 ].
Particles containing chemotherapeutic agents are engulfed by phagocytes and rapidly cleared by the reticuloendothelial system RES. A variety of strategies were developed to sustain the nanoparticles in blood stream one of which is the alteration of the polymeric composition of the carrier. Nanoparticles are coated with hydrophilic polymers to avoid wash out and remain in the bloodstream for a longer period of time that can sufficiently target cancerous cells. Hydrophilic polymer coating on the nanoparticle surface repels plasma proteins and escapes from being opsonized and cleared.
Commonly used hydrophilic polymers include polyethylene glycol PEGpoloxamines, poloxamers, polysaccharides, and so nanorobots in cancer treatment pdf [ 2930 ]. Cancerous cells have some unique properties that differentiate them from the healthy cells at molecular level. Some receptors are over expressed on the surface of them that nanorobots in cancer treatment pdf the distinguishing feature.
Attachment of the complementary ligands on the surface of nanoparticles makes them able to target only the nanorobots in cancer treatment pdf cells. Once the nanoparticles bind with the receptors, they nanorobots in cancer treatment pdf undergo receptor-mediated endocytosis or phagocytosis by cells, resulting in cell internalization of the encapsulated drug.
Numerous works are being done to investigate these ligand-receptor interactions and utilize them for clinical use [ 5 ]. Folate receptors are overexpressed in many neoplastic cells providing a target for certain anticancer therapies. Utilizing the concept, researchers are designing the surface of nanoparticles with folic acid [ 31 — 33 ]. Folic acid targeted daunomycin-HPMA conjugates were found to increase both the number of survivors and the survival time of tumor-bearing mice. The data indicate that folic acid may be highly effective in enhancing the efficacy of other polymer-bound cytotoxins [ 34 ].
Another study was done by a team led by Kukowska-Latalloto et al. The mice were injected with the nanoconjugates twice a week via a lateral tail vein. Nanorobots in cancer treatment pdf results showed that conjugated methotrexate in dendrimers significantly lowered toxicity and resulted in a fold higher efficacy compared to free methotrexate at an equal cumulative dose.
As a result, mice survived longer [ 33 ]. The efficacy of nanosized folate receptor-targeted doxorubicin aggregates was tested for cancer treatment.
Doxorubicin-polyethylene glycol-folate conjugate micelles were prepared that were nm in average diameter. The polymeric micelles exhibited enhanced and selective targeting to folate receptor positive cancer cells in vitro. The in vivo animal experiments showed that the nanoaggregates caused significant tumor suppression [ 3536 ].
Some other preparations include nanoparticles to which folate was conjugated covalently using surface carboxyl groups as well as conjugation of folate to hydrazine modified poly-lactic acid nanoparticles. Isobutyl-cyanoacrylate IBCA nanocapsules were prepared and coated with folate that showed a significantly increased efficacy of nanocapsules targeted to the tumor [ 8 ]. The experiments showed folate receptors can be targeted very effectively for selective drug delivery by nanoparticles conjugated to folic acid.
Nanoparticles are widely being investigated to target the transferrin receptors for binding and cell entry, as these are overexpressed by certain tumor cells to increase their iron uptake. Transferrin Tf can be conjugated to a variety of materials for cancer targeting which include Tf-chemotherapeutic agent, Tf-toxic protein, Tf-RNases, Tf-antibody, and Tf-peptide [ 3738 ]. The Tf-lytic hybrid peptide showed effective cytotoxic activity where normal cells were less sensitive to this molecule.
Thus the intravenous administration of Tf-lytic peptide in the athymic mice model significantly inhibited tumor progression [ 37 ]. The transferrin-modified nanoparticles are effective for systemic delivery of nucleic acid therapeutics for metastatic cancer [ 3940 ]. Luteinizing Hormone-Releasing Hormone Receptor. Luteinizing hormone-releasing hormone LHRH is being used in many ongoing researches as a targeting moiety ligand to LHRH receptors that are over-expressed in the plasma membrane of various types of cancer cells like breast cancer, ovarian cancer, and prostate cancer [ 4142 ].
They laced tailor-made tiny sponge-like nanoparticles with the drug, docetaxel. The particles were particularly designed to dissolve nanorobots in cancer treatment pdf drug in a cell's internal fluids, controlling the release rate.
The aptamers specifically recognize the surface molecules on cancer cells. In addition, the nanoparticles nanorobots in cancer treatment pdf contained polyethylene glycol molecules to keep them away from being rapidly destroyed by macrophages [ 43 ]. A team, led by Prasad, developed a method of targeting LHRH receptor with ferric oxide nanoparticles which was prepared by a reverse micelle colloidal reaction. The hydrophilic groups were sequestered in the micelle core and the hydrophobic groups remained solvent exposed on the surface of the micelle in a reverse micelle system which was formed by a surfactant, continuous oil phase, and water.
Silica was added to form the structure of the silica nanorobots in cancer treatment pdf before additional silica shell grown by tetraethylorthosilicate hydrolysis.
The targeting agent LHRH was coupled to the silica shell through carbon spacers so as to prevent stearic hindrance during the interaction of the targeting agent with its complementary molecule on cells. After the administration of the nanoparticles, the patients were exposed to a DC magnetic field. The selective interaction, internalization, and so forth were investigated by using LHRH receptor expressing cells on oral epithelial carcinoma cells.
Data clearly showed nanorobots in cancer treatment pdf the nanoparticles selectively interacted with the specific cell types [ 8 ].
Asialoglycoprotein ASGPanother receptor which is overexpressed in hepatoma, is utilized in cancer targeting by nanoparticles for anticancer drug delivery.
Sung and coworkers developed a new strategy by which biodegradable nanoparticles with a mean size of nm can be prepared to target the hepatoma cells. They prepared them from poly - -glutamic acid -poly lactide block copolymers loaded with paclitaxel using emulsion solvent evaporation technique.
Immunofluorescence analysis utilizing a rhodamine probe, encapsulated in the hydrophobic core of the gal-nanoparticles, revealed the high degree of selectivity of the nanoparticles to hepatic tumors with enhanced cellular uptake through receptor-mediated endocytosis resulting in subsequent release of the encapsulated paclitaxel inside the cytoplasm.