Nanotechnology provides new molecular contrast agents and materials to enable earlier and more accurate initial diagnosis as well as in continual monitoring of cancer patient treatment. Although not yet deployed clinically for cancer detection or diagnosis, nanoparticles are already on the market in numerous medical screens and tests, with the most widespread use that of gold nanoparticles in home pregnancy tests. For cancer, nanodevices are being investigated for the capture of blood borne biomarkers, including cancer-associated proteins circulating tumor cells, circulating tumor DNA, and tumor-shed exosomes.
Nano-enabled sensors are capable of high sensitivity, specificity and multiplexed measurements. Already clinically established as contrast agents for anatomical structure, nanoparticles are being developed to act as molecular imaging agents, reporting on the presence of cancer-relevant genetic mutations or the functional characteristics of tumor cells. This information can be used to choose a treatment course or alter a therapeutic plan.
Bioactivatable nanoparticles that change properties in response to factors or processes within the body act as dynamic reporters of in vivo states and can provide both spatial and temporal information on disease progression and therapeutic response.
Current trends and challenges in cancer management and therapy using designer nanomaterials
Current imaging methods can only detect cancers once they have made a visible change to a tissue, by which time, thousands of cells will have proliferated and perhaps metastasized. And even when visible, the nature of the tumor—malignant or benign—and the characteristics that might make it responsive to a particular treatment must be assessed through tissue biopsies. Furthermore, while some primary malignancies can be determined to be metastatic, tumor pre-seeding of metastatic sites and micro-metastases are extremely difficult to detect with modern imaging modalities, even if the tissue in which they commonly occur are known, a priori.
Finally, surgical resection of tumor tissue remains the standard of care for many tumor types and surgeons must weigh the consequences of removing often vital healthy tissue versus the cancerous mass which has grown non-uniformly within. Ultimately, removal of cancer cells at the single cell level is not possible with current surgical techniques. Nanotechnology based imaging contrast agents being developed and translated today, offer the ability to specifically target and greatly enhance detection of tumor in vivo by way of conventional scanning devices, such as magnetic resonance imaging MRI , PET , and computed tomography CT.
Moreover, current nanoscale imaging platforms are enabling novel imaging modalities not traditional utilized for clinical cancer treatment and diagnosis, for example photoacoustic tomography PAT , Raman spectroscopic imaging and multimodal imaging i. Nanotechnology enables all of these platforms by way of its ability to carry multiple components simultaneously e. NCI-funded research has produced many notable examples over the last several years. For example, researchers at Stanford University and Memorial Sloan Kettering Cancer Center developed multimodal nanoparticles capable of delineating the margins of brain tumors both preoperatively and intraoperatively.
These nanoparticles are actively targeted to the cancer with cRGDY peptides that target this specific tumor type and have already made it successfully through initial clinical trials. Another clinical cancer imaging problem being addressed by nanoscale solutions is prostate cancer. The nanoplatforms developed by this group are coupled directly to their recently approved handheld transrectal ultrasound and photoacoustic TRUSPA device. Ultimately offering a more effective, integrated and less invasive technique to image and biopsy prostate cancers for diagnosis and prognostication prior to performing common interventions surgical resection, radiotherapy, etc.
Similarly, gold nanoparticles are being used to enhance light scattering for endoscopic techniques that can be used during colonoscopies. One group at Emory University has been developing one of these for ovarian and pancreatic cancers, which are traditionally harder to deliver therapeutics to. Their platform for pancreatic cancer can break through the fibrotic stromal tissue of which these tumors are protected by in the pancreas. After traversing through this barrier, they are composed of magnetic iron cores which allow MRI contrast for diagnosis and deliver small-molecule drugs directly to cancer cells to treat.
Finally, nanotechnology is enabling the visualization of molecular markers that identify specific stages and cancer cell death induced by therapy, allowing doctors to see cells and molecules undetectable through conventional imaging.
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This is based off nanoparticles which form directly in the body after IV-injection of molecular precursors. The precursors contain specific sequences of atoms which can only form larger nanoparticles after being cleaved by enzymes produced by cancer cells during apoptosis i.
Principle of a triple-modality MRI-photoacoustic-Raman nanoparticle for clinical use. The nanoparticle is injected intravenously. In contrast to small molecule contrast agents that wash out of the tumor quickly, the nanoparticles are stably internalized within the brain tumor cells, allowing the whole spectrum from preoperative MRI for surgical planning to intraoperative imaging to be performed with a single injection. T1-weighted MRI depicts the outline of the tumor due to the T1-shortening effect of the gadolinium.
During the surgery, photoacoustic imaging with its greater depth penetration and 3D imaging capabilities can be used to guide the gross resection steps, while Raman imaging can guide the resection of the microscopic tumor at the resection margins. Raman would be used for rapid conformation of clean margins in the operating room instead of the time-consuming analysis of frozen sections. Preoperative conventional imaging tools are used to screen for disease and inform optically- driven minimally-invasive and open surgical procedures.
Clinically available particle platforms can be monitored in real-time using portable multichannel camera systems. Representative translational probes and devices for future clinical use are also shown. Nanotechnology-enabled in vitro diagnostic devices offer high sensitivity and selectivity, and capability to perform simultaneous measurements of multiple targets. Well-established fabrication techniques e. A diagnostic device or biosensor contains a biological recognition element, which through biochemical reaction can detect the presence, activity or concentration of a specific biological molecule in the solution.
This reaction could be associated, for example with: binding of antigen and antibody, hybridization of two single stranded DNA fragments, or binding of capture ligand to the cell surface epitope.
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A transducer part of the detection device is used to convert the biochemical event into a quantifiable signal which can be measured. The transduction mechanisms can rely on light, magnetic, or electronic effects. Several devices have been designed for detection of various biological signatures from serum or tissue. Few examples of diagnostic devices relying on nanotechnology or nanoparticles are given in Figure.
The bio-barcode assay was designed as a sandwich immunoassay in the laboratory of Chad Mirkin at Northwestern University. It utilizes magnetic nanoparticles MMPs which are functionalized with monoclonal antibodies specific to the target protein of interest and then mixed with the sample to promote capture of target proteins.
Target protein-specific DNA barcodes are released into solution and detected using the scanometric assay with sensitivities in femto-picomolar range.
Cancer Nanotechnology Nanomaterials for Cancer Diagnosis and Therapy
The image shows the DEAL DNA-encoded antibody library barcode assay, a high density information test for human blood proteins designed to show the individual identities of every human disease, allowing for personalized medicine. In each case, non-invasive and painless application routes have been opened by the use of nanoparticles. Furthermore, tests are currently being conducted on nanomaterials engineered with a glucose responsive coating; these can act as an insulin depot once injected under the skin.
Scientists even are working on a Type 1 diabetes vaccine by using liposomes that imitate cells in the process of natural death.
Nanotechnology and Alzheimer disease We have posted a detailed Nanowerk Spotlight on fighting Alzheimer's disease with nanotechnology , so no need to repeat that here. Nanomedicine tools for ophthalmology Most ophthalmic diseases are usually treated with topically administered drug formulations e. Nano- and microcarriers of drug substances can solve the problems with the drug delivery in the ocular tissues and nanoparticle drug delivery systems show great promise for related applications.
There are even contact lens sensors for diabetic and glaucoma diagnosis under development that some day could include for instance glaucoma drug reservoirs that could be released by a smart system whenever needed. Tissue engineering Tissue engineering is a difficult task where living cells must be organized into tissues with structural and physiological features resembling actual structures in the body.
Tissue engineering involves seeding of cells on bio-compatible scaffolds — that were fabricated through techniques like electrospinning and self-assembly — providing adhesive surfaces. Researchers though face a range of problems in generating tissue which can be circumvented by employing nanotechnology. It provides substrates for cell adhesion and proliferation and agents for cell growth and can be used to create nanostructures and nanoparticles to aid the engineering of different types of tissue. Already, researchers have developed bioactive nanoengineered hydrogels for bone tissue engineering ; designed 3D nanofiber scaffolding constructs for neural tissue engineering using stem cells; or demonstrated the fabrication of precise, biocompatible micro- and nanoscale architectures of silk proteins.
And just recently, graphene foam has been demonstrated as a scaffold for growing functional muscle tissue.
Nanomaterials for Photo-Based Diagnostic and Therapeutic Applications
Nanotechnology offers a unique opportunity to combine and improve different pharmacological profiles of antiretroviral drugs, with more convenient drug administration and potentially better patient adherence to HIV therapy. Nanotechnology solutions to combat superbugs and antimicrobial resistance Since their introduction about 70 yers ago, antibiotics have dramatically reduced deaths from infectious diseases. However, through overuse and misuse, many microorganisms have developed antimicrobial resistance AMR.
Antibiotic-resistance strains of tuberculosis TB are emerging and Methicillin-rsistant Staphylococcus aureus MRSA infections are a growing problem in hospitals. Today we are facing a global crisis in antibiotics caused by rapidly evolving resistance among microbes responsible for common infections that threaten to turn them into untreatable diseases. Every antibiotic ever developed was at risk of becoming useless. The emergence of superbugs has made it imperative to search for novel methods, which can combat the microbial resistance. For this reason, the application of nanotechnology in pharmaceuticals and microbiology is gaining importance to prevent the catastrophic consequences of antibiotic resistance.
Nanotechnology based approaches to combat superbugs are advantageous to improve various preventive measures such as coatings and filtration. Similarly, diagnosis using efficient nanosensors or probes can speed up the treatment process at an early stage of disease.
Nano-based drug carriers for existing antibiotics enhance their bioavailability and make them more targets specific. Also the combination of nanoparticles along with antibiotics makes them more lethal for micro-organisms. Probable mechanisms of nanomaterial based antibacterial solutions. Image: CKMNT Going one step further, there are efforts to replace antibiotics altogether with rapidly adaptable nanotherapeutics. They argue that recent advances in nanomaterials, genome sequencing, nucleotide synthesis, and bioinformatics could converge in nanotherapeutics with tailored sequence, specificity, and function that can overcome earlier challenges with small molecule-based approaches.
Nanosurgery Nanosurgery tools hold the promise of studying or manipulating and repairing individual cells without damaging the cell. For instance, nanosurgery could remove or replace certain sections of a damaged gene inside a chromosome; sever axons to study the growth of nerve cells; or destroying an individual cell without affecting the neighboring cells. Among the nanomanipulation techniques which exist, the atomic force microscope AFM is capable of imaging and working with extremely small structures with very high precision.
These articles might interest you as well:. Nanotechnology in healthcare Part 2: Nanomedicine therapy. In terms of therapy, the most significant impact of nanomedicine is expected to be realized in drug delivery and regenerative medicine.