File Name: nanoparticles in cancer therapy and diagnosis .zip
International Journal of Biological Sciences. Journal of Cancer. Journal of Genomics. Global reach, higher impact. Journal of Genomics - Submit manuscript now Int J Med Sci ; 17 18 Cancer is a leading cause of death and poor quality of life globally. Even though several strategies are devised to reduce deaths, reduce chronic pain and improve the quality of life, there remains a shortfall in the adequacies of these cancer therapies.
Among the cardinal steps towards ensuring optimal cancer treatment are early detection of cancer cells and drug application with high specificity to reduce toxicities. Due to increased systemic toxicities and refractoriness with conventional cancer diagnostic and therapeutic tools, other strategies including nanotechnology are being employed to improve diagnosis and mitigate disease severity. Over the years, immunotherapeutic agents based on nanotechnology have been used for several cancer types to reduce the invasiveness of cancerous cells while sparing healthy cells at the target site.
Nanomaterials including carbon nanotubes, polymeric micelles and liposomes have been used in cancer drug design where they have shown considerable pharmacokinetic and pharmacodynamic benefits in cancer diagnosis and treatment. In this review, we outline the commonly used nanomaterials which are employed in cancer diagnosis and therapy.
We have highlighted the suitability of these nanomaterials for cancer management based on their physicochemical and biological properties. We further reviewed the challenges that are associated with the various nanomaterials which limit their uses and hamper their translatability into the clinical setting in certain cancer types. Cancer is a leading cause of death and a global health burden. It was estimated that there would be Cancer is a disease characterized by uncontrolled cell proliferation that spreads from an initial focal point to other parts of the body to cause death.
For these reasons, it is key to ensure earlier detection and treatment of cancers to reduce disease spread and mortalities. Amongst the widely used strategies, today in cancer research is nanotechnology. Nanotechnology has led to several promising results with its applications in the diagnosis and treatment of cancer, including drug delivery[ 2 ], gene therapy, detection and diagnosis, drug carriage, biomarker mapping, targeted therapy, and molecular imaging.
Nanotechnology has been applied in the development of nanomaterials[ 3 ], such as gold nanoparticles and quantum dots, which are used for cancer diagnosis at the molecular level. Molecular diagnostics based on nanotechnology, such as the development of biomarkers, can accurately and quickly detect the cancers[ 4 ]. Nanotechnology treatments, such as the development of nanoscale drug delivery, can ensure precise cancerous tissue targeting with minimal side effects[ 5 , 6 ].
Due to its biological nature, nanomaterials can easily cross cell barriers[ 7 ]. Over the years, nanomaterials have been used in the treatment of tumors, due to their active and passive targeting. Although many drugs can be used to treat cancers, the sensitivity of the drugs generally leads to inadequate results and can have various side effects, as well as damage to the healthy cells.
In view of that, several studies have examined different forms of nanomaterials, such as liposomes, polymers, molecules, and antibodies, with the conclusion that a combination of these nanomaterials in cancer drug design can achieve a balance between increasing efficacy and reducing the toxicity of drugs[ 8 ].
However, due to the potential toxicity of nanomaterials, there is still a lot of advancement to be done on them before their readily acceptance in the clinic for cancer management[ 9 ]. With the rapid development of nanotechnology, this paper will review its application in cancer diagnosis and treatment with focus on their benefits and limitations during use Figure 1. Genetic mutations can cause changes in the synthesis of certain biomolecules leading to uncontrolled cell proliferation and ultimately cancerous tissues[ 7 ].
Cancers can be classified as either benign or malignant. Benign tumors are confined to the origin of cancer while malignant tumors actively shed cells that invade surrounding tissues as well as distant organs. Cancer diagnostic and therapeutic strategies are targeted at early detection and inhibition of cancerous cell growth and their spread.
Notable among the early diagnostic tools for cancers is the use of positron emission tomography PET , magnetic resonance imaging MRI , computed tomography CT and ultrasound[ 10 ]. These imaging systems, however, are limited by their inadequate provision of relevant clinical information about different cancer types and the stage.
Hence it makes it difficult to obtain a full evaluation of the disease state based on which an optimum therapy can be provided [ 11 , 12 ]. In the past few decades, the application of nanoparticles in cancer diagnosis and monitoring has attracted a lot of attention with several nanoparticle types being used today for molecular imaging.
Due to their advantages including small size, good biocompatibility, and high atomic number, they have gained prominence in recent cancer research and diagnosis.
Nanoparticles used in cancer such as semiconductors, quantum dots and iron oxide nanocrystals possess optical, magnetic or structural properties that are less common in other molecules [ 13 ]. Different anti-tumor drugs and biomolecules including peptides, antibodies or other chemicals, can be used with nanoparticles to label highly specific tumors, which are useful for early detection and screening of cancer cells[ 14 ].
For cancer diagnostics, imaging of tumor tissue with nanoparticles has made it possible to detect cancer in its early stages. Recent studies have shown a high specificity of SPIONs with no known side effects, making them suitable building blocks for aerosols in lung cancer MRI imaging[ 16 - 18 , 19 ]. Magnetic powder imaging has also been used in tomographic imaging technology where it has shown a high resolution and sensitivity to cancer tissues[ 20 ]. Further, in vitro studies using nanosystem for positron emission tomography PET have also been developed based on self-assembled amphiphilic dendritic molecules.
These dendritic molecules spontaneously assemble into uniform supramolecular nanoparticles with abundant PET reporting units on the surface. By taking advantage of dendritic multivalence and the enhanced penetration and retention EPR effect, the dendritic nanometer system effectively accumulates in tumors, resulting in extremely sensitive and specific imaging of various tumors while reducing treatment toxicities.
In current research, nanotechnology can validate cancer imaging at the tissue, cell, and molecular levels[ 20 ]. This is achieved through the capacity of nanotechnology applications to explore the tumor's environment, For instance, pH- response to fluorescent nanoprobes can help detect fibroblast activated protein-a on the cell membrane of tumor-associated fibroblasts[ 21 ].
Hereon, we will discuss some nanotechnology-based spatial and temporal techniques that can help accurately track living cells and monitor dynamic cellular events in tumors.
The lack of ability to penetrate objects limits the use of visible spectral imaging. Quantum dots that emit fluorescence in the near-infrared spectrum i. A second near-infrared NIR window NIR-ii, nm with higher tissue penetration depth, higher spatial and temporal resolution has also been developed to aid cancer imaging.
Also, the development of a silver-rich Ag2Te quantum dots QDs containing a sulfur source has been reported to allow visualization of better spatial resolution images over a wide infrared range[ 25 ].
Another commonly used nanotechnology application is the use of nanoshells. Nanoshells are dielectric cores between 10 and nanometers in size, usually made of silicon and coated with a thin metal shell usually gold [ 26 , 27 ].
Nanoshells are desirable because their imaging is devoid of the heavy metal toxicity[ 28 ] even though their uses are limited by their large sizes. Gold nanoparticle AuNPs is a good contrast agent because of its small size, good biocompatibility, and high atomic number. Research shows that AuNPs work by both active and passive ways to target cells.
The principle of passive targeting is governed by a gathering of the gold nanoparticles to enhance imaging because of the permeability tension effect EPR in tumor tissues[ 29 ]. Active targeting, on the other hand, is mediated by the coupling of AuNPs with tumor-specific targeted drugs, such as EGFR monoclonal antibodies, to achieve AuNP active targeting of tumor cells Figure 2.
When the energy exceeds 80kev, the mass attenuation rate of gold becomes higher than alternative elements like iodine, indicating a greater prospect gold nanoparticles [ 30 ]. Rand et al. These findings have important implications for early diagnosis, with the technique allowing tumors as small as a few millimeters in diameter to be detected in the body[ 31 ].
Cancer biomarkers are biological features whose expression indicates the presence or state of a tumor. Such markers are used to study cellular processes, to monitor or identify changes in cancer cells, and these results could ultimately lead to a better understanding of tumors. Biomarkers can be proteins, protein fragments or DNA.
Among them, tumor biomarkers, which are indicators of a tumor, can be tested to verify the presence of specific tumors. Under current medical conditions, biomarkers from blood, urine, or saliva samples are used to screen individuals for cancer risk. But these biomarkers have not proven adequate for cancer screening. Therefore, several researchers have resorted to the study of extract patterns of abnormally expressed proteins, peptide fragments, glycans and autoantibodies from serum, urine, ascites or tissue samples from cancer patients[ 33 - 35 ].
With the development of proteomics technology, protein biomarkers for many cancers have been discovered. In general, protein profiling tests would remove the high molecular weight proteins such as albumin and immunoglobulins. However, the removal of these proteins also removes the low molecular weight protein biomarkers conjugated to them, resulting in the loss of the biomarkers of interest.
These low molecular weight proteins represent a potential biomarker-rich population[ 36 - 38 ]. Two studies led by Geho and Luchini came up with the method of capturing and enriching low molecular weight proteins by nanoparticles to obtain biomarkers from biological liquids, thus improving the screening of biomarkers[ 39 , 40 ].
Nanoparticles compete with the carrier proteins by their surface characteristics, such as electric charge, or functional biomolecules, which are currently possessed by mesoporous silica particles, hydrogel nanoparticles, and carbon nanotubes[ 39 - 46 ]. Another method to improve screening with nanocarrier is to improve the sensitivity of mass spectrometry. The unique optical and thermal properties of carbon nanotubes enhance the energy-transfer efficiency of the analyte, contributing to the absorption and ionization of the analyte, and eliminate the interference of inherent matrix ions[ 46 - 48 ].
A third approach is to use nanotechnology to make lab-on-chip microfluidics devices that can be used for immuno-screening or to study the properties of tumor cells. Another example is that cells growing on the surface of different sized nanometres, which were discovered by these nanometres across can differentiate between tumor cells[ 50 ].
Suffice it to say that there are still false-positive and false-negative results from screening of biomarkers by nanotechnology, and we need to improve sensitivity without compromising specificity. Various types of gold nanoparticles different sizes, morphologies, and ligands accumulate in tumor tissues by the action of osmotic tension effect termed Passive targeting or localize to specific cancer cells in a ligand-receptor binding way termed Active targeting.
The development of nanotechnology is based on the usage of small molecular structures and particles as tools for delivering drugs. Nano-carriers such as liposomes, micelles, dendritic macromolecules, quantum dots, and carbon nanotubes have been widely used in cancer treatment. Liposomes are one of the most studied nanomaterials, which are nanoscale spheres composed of natural or synthesized phospholipid bilayer membrane and water phase nuclei[ 51 ].
Because of the amphiphilicity of phospholipids, liposomes form spontaneously[ 51 ], allowing hydrophilic drugs to preferentially stay in the monolayer liposome while hydrophobic ones form before the multilayer liposome[ 52 ]. Some drugs could be incorporated into liposomes by exchanging them from acidic buffer to the neutral buffer.
Neutral drugs can be transported in liposomes also, but due to a poor avidity for acidic environments, they are not readily released from the inside of the liposomes[ 53 ].
Other mechanisms of drug delivery are the combination of saturated drugs with organic solvents to form liposomes[ 51 ]. Under the influence of the EPR effect[ 53 ], the vesicle of size around kDa or nm can be allowed into the tumor by the gaps in vessels[ 52 ]. In tumors they can fuse with cells, are internalized by endocytosis, and release drugs in the intracellular space[ 52 ]. In the case of the appropriate pH, redox potential, ultrasonic and under the electromagnetic field, the liposome can also release the drug through passive or active ligand-mediated activity[ 52 ].
The targeted therapy has an advantage in the vascular system, micrometastases, and blood cancers[ 54 ]. It has been shown that the half-life of liposome is affected by size. The liposome up to nanometers easily penetrate the tumor and stay longer, while the half-life of the bigger liposome is shorter because they are easily recognized and cleared by the mononuclear phagocyte system[ 55 ]. Liposome-bound antibodies target tumor-specific antigens to ensure active targeting and then transport drugs to the tumor.
With a lot of pharmacokinetic benefits, some liposomal drugs are approved for clinical therapy Table 1. For instance, liposomal forms of adriamycin have been used for the management of metastatic ovarian cancer where they have shown appreciable clinical benefit[ 56 , 57 ].
Chapter 5: RIPL peptide as a novel cell-penetrating and homing peptide: design, characterization, and application to liposomal nanocarriers for hepsin-specific intracellular drug delivery. Chapter Multifunctional polymeric micelles as therapeutic nanostructures: targeting, imaging, and triggered release. Chapter Recent advances in diagnosis and therapy of skin cancers through nanotechnological approaches. Chapter Recent advances of folate-targeted anticancer therapies and diagnostics: current status and future prospectives. Chapter Dose enhancement effect in radiotherapy: adding gold nanoparticles to tumor in cancer treatment. Chapter Ligand-decorated polysaccharide nanocarriers for targeting therapeutics to hepatocytes. Chapter Combination therapy of macromolecules and small molecules: approaches, advantages, and limitations.
Kumar Bishwajit Sutradhar, Md. Nanoparticles are rapidly being developed and trialed to overcome 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 inability 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 interaction with the healthy cells.
Request PDF | Nanoparticles in cancer therapy and diagnosis | Numerous investigations have shown that both tissue and cell distribution profiles of anticancer.
Although cancer survival rates have remarkably increased over the past 50 years, those in late stage cancers remain low such as glioma, pancreatic cancer, liver cancer, breast cancer, etc. Global researchers are working hard to find cures for these cancers. Among several emerged technologies over the past two Among several emerged technologies over the past two decades e. Nanoparticles possess several advantages such as combination therapy, tumor targeting, controlled release, long circulation, reduced toxicity and concurrent live imaging. Nanoparticles, constructed from lipids, proteins, polymers e. PLGA , drug molecules or inorganic materials e.
International Journal of Biological Sciences. Journal of Cancer. Journal of Genomics. Global reach, higher impact. Journal of Genomics - Submit manuscript now
The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy. Chemotherapeutic drugs are toxic against cancer cells, but due to their low specificity and high toxicity, these drugs are also toxic for healthy cells. This toxic reaction occurs because medications, in general, are small enough molecules to pass through the endothelium in almost all regions of the organism after systematical administration, and they can reach both target regions and other regions not affected by the disease, therefore, originating a number of side effects associated with the medication. A possible strategy that may improve therapeutic efficacy of chemotherapeutic agents and decrease its side effects entails the use of colloidal nanoparticle systems.
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