Over the past few years, tremendous attention has been given to the cancer related research and developments. There has been an outstanding progress in the basic cancer biology. Many institutions, pharmaceutical and biotechnological industries have focused on cancer as their main target in their research and development departments. However, in spite of this progress in cancer research, comparable advances in cancer therapeutics have not taken place. The main reason for this failure was inability to deliver therapeutic moieties that selectively reach the desired targets which also resulted in unintended effects.
Nanotechnology in cancer:
To subside the disadvantages of conventional cancer therapeutics, Nanotechnology has been given considerable attention. Nanotechnology may be defined as the creation of materials, drugs and devices that are used to manipulate matter that are of nanolevel size (1-100nm).
Nanomaterials, due to their extremely small size, are readily taken up by the human body. In contrast to normal larger sized particles, they can cross the biological membranes and reach the cells, tissues and organs with ease. Nanoparticles are colloidal dispersions of biodegradable polymers. Drugs can be enclosed, entrapped or adsorbed onto the particle surface or dissolved within the matrix. They have large surface area to volume ratio that aids in their diffusion through the membranes.
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Nanotechnology has found its applications in many fields including chemistry, pharmacology, novel drug delivery systems, biotechnology to name a few. Many different types of nanosystems have been utilized in diagnostics and therapeutics of various diseases. These may include silica based nanoparticles, gold nanoparticles, polymer based nanoparticles, dendrimers, liposomes, paramagnetic nanoparticles. An example of their application is liposomal based drug delivery system of Doxorubin for the treatment of breast and ovarian cancer.
Current cancer nanotechnologies:
In this section, the current nanotechnologies that have been utilized in cancer will be discussed. These mainly include arrays of nanocantilevers, nanotubes and nanowires for multiplexing detection, multifunctional injectable nanovectors for therapeutics and diagnostics and magnetic resonance imaging (MRI) contrast agents for neurooncological interventions.
Nanovectors have been used on a large scale as nanotechnological devices in cancer. They have been used as intravascular injectables for drug delivery and imaging in cancer. They are hollow or solid structures which can be filled with various anticancer drugs, targeting moieties and detection agents. Their size can range from 1-1000nm.
Liposomes are the simplest forms of nanovectors which are made up of lipids enclosing water core. Enhanced permeation and retention effects are their major delivery strategies. With the aid of over expression of fenestrations in cancer neovasculature, they increase the drug concentration at the tumour sites (passive targeting). Various Doxorubin encapsulated liposomal formulations have beeen clinically utilized for the treatment of Kaposiâ€™s sarcoma, breast cancer and refractory ovarian cancer. They were developed to improve therapeutic index of the conventional Doxorubin chemotherapy while maintaining its antitumour activity.
Nanovectors may be classified into different generation nanovectors.
The first generation nanovectors are not targeted specifically against any biological molecule on the tumour cells. An example of this would be albumin bound Paclitaxel. It has found its application in breast cancer chemotherapy. This chemotherapy enabled to overcome solubility problems related to Paclitaxel and improve the toxicity profile of conventional Paclitaxel therapy.
The second generations of nanovectors were evolved for specific targetting. These nanovectors were developed to recognize and target specific biological molecules on the cancer cells (active targetting). This reduces the toxicity and would also improve therapeutic index. Coupling of high affinity ligands and specific antigens on the surfaces of nanoparticles is an example of this generation of nanovectors. As compared to the first generation, they have improved biodistribution. The antigens on the cancer cells allows efficient uptake of targeted drugs through endocytosis (receptor mediated). The active drug delivery consists of several components like drug conjugated polymer and ligands / antibodies which are specific and bind to the specific tumour antigens / receptors.
The third generation of nanovectors is currently under development which is multi stage strategy based. The first stage particle can be biodegradable silicon microparticles which are having pores within them. They are designed to pass through the circulatory system and recognize the disease specific endothelium. The second stage particles are multitypes of nanoparticle which are loaded within the first stage particles. They are within the pores of the first stage particles and are set free towards the tumour mass. They are small enough (less than 20nm) to easily cross the inter-endothelial junctions. They contain different payloads for therapy and imaging, They can effectively be utilized for cancer in future.
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Several types of nanoparticles have been developed and utilized in MRI contrast. These include iron oxide based nanoparticles, gadolinium based nanoparticles to name a few. Low density lipid nanoparticles have been developed to increase ultrasound imaging. Multimode imaging contrast nanoagents have also been developed combining biological targetting and magnetic resonance. Biodegradable porosified silicon has also been utilized for injectable nanovectors. Many polymer based nanovectors have also been developed. Besides these, Dendrimers have also been utilized in cancer. They are self assembling synthetic polymers which were used in the MRI of lymphatic drainage in mouse model of breast cancer. Nanoshells are others which are being lined up in cancer therapeutics and diagnostics. They are composed of a gold shell surrounding a semiconductor. When they reach the cancer cells, they can be irradiated. These irradiations make them hot which ultimately kill the cancer cells. This technique has been successfully utilized in veneral tumours in mice.
Varied types of novel devices are emerging with potential applications in cancer. Nanobiosensors have been developed for cancer diagnostics. A device used for analyte detection through combination of a biological component with a detector component is termed as a biosensor. These nanoscale sensors comprise of cancer specific antibody or ligands so that they can selectively capture cancer cells or target proteins. This yields mechanical, optical or electrical signals which can be detected by the detector. For detection of DNA, Quantum dots based sensor has also been developed. Multimolecular mechanical sensing devices like nanocantilevers have also been emerged as one of the promising approach. Nanocantilevers comprise of large number of beams. When biomolecules of interest bind, deflection of beam take place which is observed by laser light or other methods. The flexible beams are coated with molecules capable of binding to cancer biomarkers.
Nanowires, fullerenes and nanotubes are amongst others which are considered for cancer therapeutics and diagnostics. Fullerenes are nanostructured arrangement of carbon atoms in specific soccer like architecture. They may also form nanotubes which are cylindrical carbon atom assemblies. Nanotubes and fullerenes have found several specific sensing applications. For instance, Nanotubes have been developed as high specificity sensors of antibody signatures of autoimmune diseaseand SNPs (single nucleotide polymorphism). Nanowires are other class of nanotechnology that has been developed. They are sensing wires coated with antibodies like molecules to bind to proteins of interest. Silicon nanowires are one such real time detectors for simultaneous molecular binding effects.
Present challenges and future prospects:
The application of nanotechnology in clinical use in cancer has found several drawbacks and challenges. Endothelial cell barriers on vessels, cellular uptake of therapeutic agent, clearance of drugs from circulation, heterogeneity among tumours are the present challenges.
To conclude, the present cancer therapy needs advancement and cancer nanotechnology definitely can provide a breakthrough to eradicate cancer related death. Varied types of nanodevices have been developed which can effectively be applied in cancer therapeutics and diagnostics. Still extensive research needs to be carried out for effective utilization of cancer nanotechnology in clinic. There is need to identify favorable physiochemical properties and favorable nanodevices that will help to overcome multiple barriers.