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| REVIEW ARTICLE |
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| Year : 2020 | Volume
: 7
| Issue : 2 | Page : 40-44 |
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An Overview on the Application of Nanodiagnostics in Cancer
Kavita Gala, Ekta Khattar
Department of Biological Sciences, Sunandan Divatia School of Science, SVKM's NMIMS (Deemed to be University), Mumbai, Maharashtra, India
| Date of Submission | 04-Dec-2020 |
| Date of Decision | 18-Dec-2020 |
| Date of Acceptance | 18-Dec-2020 |
| Date of Web Publication | 31-Dec-2020 |
Correspondence Address:
Dr. Ekta Khattar
Sunandan Divatia School of Science, SVKM’s NMIMS (Deemed to be University), Mumbai, Maharashtra
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/bmrj.bmrj_14_20
In the battle against cancer, timely diagnosis is critical for successful treatment. The major limitation in detecting cancer at early development stages is the unavailability of sensitive and specific detection methods. Nanobiology combines biology with physics and chemistry to generate several new areas such as nanodiagnostics and nanotheranostics. Nanodiagnostics involve the development of new strategies and innovations to enhance the current detection methods in tumor biology. Another important aspect of nanodiagnostics is to improve personalized cancer detection and real-time monitoring of treatments assisted by imaging modalities. Nanotheranostics combines therapy and diagnosis in a single model for cancer detection and treatment thus providing the advantage of targeted drug delivery and fewer side effects to normal tissues. In this review, we have outlined diverse nanoparticle systems for early cancer detection and therapy. A wide variety of nanomaterial-based approaches such as nanobubbles, quantum dots, liposomes, or nanotubes demonstrate huge potential in improving imaging methods to screen and monitor cancer progression. Although a significant amount of contributions have been directed to develop nanodiagnostics systems, they are still at preclinical stage. Thus, it is a dynamic area for research with encouraging development towards the clinical stage.
Keywords: Cancer biomarkers, cancer imaging, gold nanoparticles, nanobiology, nanotheranostics
How to cite this article:
Gala K, Khattar E. An Overview on the Application of Nanodiagnostics in Cancer. Biomed Res J 2020;7:40-4 |
| Introduction | |  |
Cancer
Cancer is the uncontrolled growth of cells due to loss of tumor suppression and activation of oncogenes.[1] Despite huge technological and pharmaceutical development, it is one of the leading cause of death. Thus, cancer burden continues to increase worldwide.[2] Early diagnosis of cancer is one of the major step towards reducing the diseases burden globally.
The primary purpose of cancer detection and screening is to provide treatment at the earliest by identifying lesions or uncontrolled growth in cells at an early stage.[3] Cancer progression is known to occur with changes in cellular metabolism.[4] The identification and quantification of cancer-associated markers from patient samples help in monitoring the progression or treatment in cancer patients.[5] To date research in this field is escalating and several tools have been developed for better cancer screening and monitoring.[6]
Current diagnostic methods
- Tissue biopsy is the standard method used in cancer diagnosis. The tissue samples are studied microscopically for changes in histology, biological markers, or the presence of metastasis.[7] A breakthrough in biopsies is the development of a noninvasive sampling method known as liquid biopsy which investigates circulating tumor cells or cell-free DNA released by tumor cells[8]
- Biomedical imaging is another essential tool in cancer diagnostics. Imaging techniques provide structural, morphological, and functional information on tumors. X-rays, computed tomography (CT) scans, mammograms, ultrasound, magnetic resonance imaging (MRI), positron emission tomography (PET), and nuclear medicine scans are a few of the imaging techniques used to image body organs to diagnose cancer. A combination of these systems such as PET/CT, PET/MRI/ultrasound provide complementary data for better staging and therapy[9]
- Molecular techniques have also been utilized in cancer diagnosis, prognosis, metastasis, relapse, and treatment. Many molecular biomarkers have been used such as altered genes, altered pathways, and chromosomal aberrations. Some examples include receptors of epithelial growth factor, vascular endothelial growth factor (VEGF), and estrogen receptor.[10]
However, these methods have a lot of limitations. For example they can only identify cancers once tumors become visible. In addition, biopsies only provide a glimpse of the disease, are tough to extract in certain cases, and result in pain during the development of treatment. Simultaneously in patients, thousands of cells have divided and metastasized. These represent major challenges in the current methods used in the diagnosis of cancer.
Nanobiology
Nanobiology combines several streams of science including physics, engineering, chemistry, and material science with biology. This inter-disciplinary field addresses various biological problems, including the detection of cancer.[11] Nano-based technologies are still under investigation for cancer diagnosis in imaging and monitoring of biomarkers and have shown promising results.[12] An important benefit of using the small-sized particles is their large surface area to volume ratio. This advantage allows the coating of nanoparticles with ligands and improves the specificity and sensitivity of detection.[13] In this review, we discuss a diverse nanoscience-based system for early cancer detection and therapy and addressed the prospects in the application of nanodiagnostics in cancer studies.
Nano diagnostics in cancer
The expansion in the field of screening technologies has aided detection at the anatomical and functional level. The development of novel probes; contrasting agents for imaging, identification of biomarkers has improved cancer detection, monitoring, and treatment.[14] With the help of specifically designed nanoparticles, such as quantum dots (QDs), nanotubes, nanorods, and nanowires, cancer detection is possible at the early stages.[15],[16],[17],[18] Diagnostic kits using nanoparticles offer a more selective and sensitive method that can detect minor changes at the cellular and molecular level.[14]
Nanoparticles for cancer imaging
One of the important components in the diagnosis of cancer is imaging which is regularly used to screen and monitor the progression of tumors. Many imaging methods are currently in use but now several studies are employing nanoparticles for enhancement of these methods. Various developments have been made in imaging methods such as sonography, MRI, fluorescence imaging, and photoacoustic imaging to make them more efficient.
Sonography imaging has been modified with the use of polymer-based nano-bubbles as contrasting agents which are dispensed intravenously and detected by contrast-enhanced ultrasound. The most commonly used nano-bubbles are composed of phospholipid shells with gas core and are studied in vitro as well as in vivo.[19],[20],[21]
Gadolinium (Gd)-based nanoparticles or super magnetic iron oxide nanoparticles (SPIONs) have been developed as contrast agents for the MRI method. Several SPIONs are undergoing clinical trials such as ProHance® a Gd-based nanoparticle and Ferumoxytol iron-based nanoparticles are used in clinical care to study brain tumors. Both the contrasting agents were able to differentiate between metastatic brain disease and meningioma after 24 h of injection in MRI scans.[22]
QDs are small semi-conductor particles that emit light at particular frequencies when electricity or light is employed to them. In vivo studies in cancer suggest that QDs gather at the tumor site by increased permeability and retention or by binding with antibodies to cancer biomarkers.[15] Simultaneous detection of five cancer biomarkers in breast cancer correlated with traditional methods implying that QD technology is suitable for profiling multiple markers for better prognosis.[23]
CT scans and X-rays are commonly used for cancer screening. Nanoparticles based preclinical studies are carried out using iodine-containing liposomes, gold nanorods, and lanthanide oxide for imaging cancer cells.[24],[25],[26] The application of gold and iodine nanoparticle enhanced tumor contrast in CT scanning and provided better morphological information about the tumor.[27]
The ultrasound imaging technique is used to detect cancer masses majorly because of its low cost, real-time viewing ability, and nonradioactive agents. Various nanoparticles such as SPIOs, gold nanoparticles (GNPs), lead nanoparticles are used as contrast agents for ultrasound imaging.[28] Photoacoustic imaging is an advancement of the ultrasound method which uses pressure waves for the detection of cancer. Preclinical studies have employed GNPs and carbon nanotubes to image cancer lesions.[29]
Nanoparticles for cancer biomarkers
Screening for biomarkers includes investigating the presence of markers that are specific to cancer. The aim is to find molecular patterns or signatures for each type of cancer with respect to its stage, grade, and signature to determine the therapy. Various proteins are approved by country specific approval authorities for cancer detection such as serum alfa-fetoprotein for liver cancer, prostate-specific antigen (PSA) for prostate cancer, CA-125 for ovarian cancer, and carcinoembryonic antigen (CEA) for colon cancer.[30] Nanoparticles are engineered with antibodies, ligands, or aptamers to target these markers. The interaction is then transformed into a measurable signal and quantified.[31]
Silicon nanowires have been used to detect protein biomarkers such as PSA, RNA of cancer-testis antigens, VEGF, and CEA in cancer patients.[16],[32],[33],[34] Likewise, silicon nanowires with peptide nucleic acid or DNA probes were used to detect microRNAs or their DNA analogs.[35]
GNPs conjugated with single chain variable fragment antibody have been used to target EGFR in vitro and in vivo. These GNPs were 200 times brighter than near infrared (NIR)-based QDs and could detect small tumors.[36] A combination of GNPs and nanorods coated with PSA antibody was designed as a one-step homogenous assay for tumor detection. It was able to detect biomarkers at low concentration.[17] Arg-Gly-Asp (RGD) is recognized by integrin αvβ3 receptor and is elevated on cell surfaces implying metastasis and angiogenesis and has been targeted in vivo using nanoparticles in breast cancer glioma xenografts.[37],[38] GNPs and carbon nanotubes are in clinical trials to identify volatile organic compounds such as acetaldehyde, formaldehyde undecane, and ethylbenzene in the breath of individuals with lung cancer.[18]
Aptamers are ssDNA or RNA oligonucleotides with high annealing potential with their target sequences. For example cyanin-5 dye conjugated to polylactic acid (Cy5)/aptamers NPs successfully bind to prostate cancer cells positive for prostate-specific membrane antigen, in vivo these nanoparticles exhibit high-intensity fluorescent signals with a minimum background.[39]
A DNA silver nanocluster probe has been designed for the detection of an exon in the BRAC1 gene to diagnose breast cancer. The hybridized nanoclusters were able to efficiently distinguish different deletions in BRCA1.[40]
Another promising development in the field of nanodiagnostics is the application of nanodevices activated by multiparameter stimuli. Nanodevices are nanorobots designed to study biomarkers for cancer imaging.[41] Tang and colleagues developed a dual “lock and key” nanodevice using hyaluronic acid chains and disulfide bonds to quench the fluorescence of NIR-II cyanine dyes. Overexpression of hyaluronidase and thiols in cancer cells act as a dual key to disengage the lock state of NIR-II cyanine dye. This strategy resulted in low background fluorescence and enhanced specificity in breast cancer imaging.[42]
| Nanotheranostics in Cancer | | |
Nanotheranostics represents the simultaneous integration of nanotechnology, diagnosis, and therapy. Nanotheranostics is to further advance the development of nanomedicine strategy to provide continuous, regulated, and targeted delivery for better diagnosis and therapeutic effect with lesser side effects.[43] Hence, nanotheranostics are an attractive strategy for both diagnostic and therapeutic studies and have been exclusively investigated as a nanocarrier system.[44]
Current findings have led to the development of theranostic that include double or triple actions. Magnetic nanoparticles covered with albumin were developed as VEGF targeted nanosystem loaded with doxorubicin and conjugated with antibodies for VEGF. The magnetic core enabled detection by MRI postinjection in breast cancer models.[45] Liposomes functionalized with gonadorelin (overexpressed in cancer) were developed and loaded with magnetic iron oxide nanoparticles and mitoxantrone (a chemotherapeutic agent). The integration of therapy and imaging technique efficiently reduced tumor development and provided real-time noninvasive imaging of the system.[46] Recently, a group of researchers developed a multimodal system made of branched glycopolymer in combination with paclitaxel (PTX) as a chemotherapeutic drug and MRI contrasting agent gadolinium-tetra-azacyclo-dodecatetraacetic acid. The resulting system showed better pharmacokinetics and better accumulation at the tumor site and brighter MRI scans for up to 24 h. It also exhibited more than 90% efficacy compared to the free PTX in in vivo cancer model.[47]
The tumor microenvironment has an acidic pH, hypoxia condition, higher expression of biomarkers, active efflux pumps, and hyperthermia compare to the environment near normal cells.[48] To exploit these characteristics, light-responsive graphene nano-gel have also been developed. The nano-gel combined with doxorubicin and a pH-sensitive hyaluronic acid has been investigated in inhibiting lung cancer. Graphene on itself was photoluminescent and worked as both, contrasting agent and heat source.[49] Another approach was the application of EGFR targeted liposomes encapsulated with doxorubicin and small interfering RNAs along with iron oxide nanoparticles with a mesoporous silica shell. The response to pH was ensured by loading the system with ammonium bicarbonate gradient which selectively targeted pancreatic cancer cells.[50]
In the present and future period of personalized medicine, nanotheranostics provides an important tool to select the most appropriate therapy and monitor cancer progression. An example of a study in this area was carried out in the triple-negative breast cancer model (TNBC). Long-circulating liposomes were developed and loaded with doxorubicin, gemcitabine, or cisplatin and the corresponding DNA barcode to screen TNBC. Fluorescent imaging by indocyanine green demonstrated that the system was able to specifically target cancer cells. Hence, nanotheranostics can be an attractive strategy in the field of personalized medicine.[51]
| Future Prospects | | |
Biomedical nanotechnology can extend the boundaries of present diagnostics and therapeutics and facilitate progress in the field of personalized medicine. In the coming years, the tools will be widely used in diagnosis for screening, monitoring, and treating cancer cells. [Figure 1] shows a summary of current uses of nanomaterials in cancer biology. Nanodiagnostics are an emerging field which is employing novel strategies and innovations, with the aim to improve current detection methods in tumor biology. The advancement in noninvasive imaging techniques and identification of biomarkers is made possible due to newer single and multimodal methods. The identification of biomarkers provides a more quick and targeted evaluation of the progression of cancer. Nanotheranostics in the coming years will play important roles in combined detection and treatment systems and also aid in the expansion of personalized medicine. Nano-based theranostic modalities enhance their solubility, increase their stability, and inertly target cancer cells. Despite the increase in new strategies for early detection and therapy of cancer, very few reach clinical trials. Besides, several drawbacks regarding safety and efficacy need to be addressed. With that aim, multi-disciplinary co-operation is required between clinicians, biologists, chemists, and material scientists to present novel theranostic approaches to the patients. | Figure 1: Schematic representation presenting various aspects of nanodiagnostice in cancer
Click here to view |
Financial support and sponsorship
EK is supported by a Research Grant from the Department of Biotechnology (No. BT/RLF/Re-entry/06/2015), Department of Science and Technology (ECR/2018/002117) and NMIMS Seed Grant (IO 401405).
Conflicts of interest
There are no conflicts of interest
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