Nanoparticles As Targeted Therapies : A New Generation Of Cancer Treatments

Hugh Savagè has liver cancer. Chemotherapy failed, surgery failed. In a last ditch attempt to save his own life, Hugh signs up for a miracle trial using nanotechnology. In this trial, the widely-used chemotherapy drug Epirubicin was attached to nanodiamonds (carbon structures with a diameter of about five nanometres) to cultivate a nanodiamond-Epirubicin drug delivery complex (EPND). Researchers have found that while both the usual Epirubicin and EPND are capable of killing normal cancer cells, only EPND is capable of killing chemo resistant cancer stem cells and preventing secondary tumour formation in xenograft models of liver cancer.

Niosomes can alter the metabolism; prolong circulation and half life of the drug, thus decrease the side effects of antineoplastic drugs. Niosomally entrapped methotrexate and doxorubicin showed beneficial effects over the free drug, such as decreased rate of proliferation of the tumor and higher plasma levels accompanied by slower elimination (9).

Pharmacokinetic analysis suggests that the orally administered nanoemulsions had a higher rate of absorption and the concentration of the drug in the brain and plasma was the highest. Formulation: The drug nanoemulsion was prepared by adding 50% of the drug solution (with dehydrated ethanol) to one ml of safflower oil and it was stirred for the oil drug mixture to distribute homogenously and for all the ethanol to evaporate. Deionized distilled water (contains egg phosphatidylcholine) and deoxycholic acid.(40mg) make up the aqueous phase. Both the phases are heated at 70oc separately. The oil phase was slowly added to the aqueous phase and stirred well. The mixture was then sonicated (21% amplitude and 50%duty cycle). The mixture formed (drug containing nanoemulsion) was then filtered and stored at 4oc.Preparation of aqueous suspension was made using 3H Labeled drug and unlabeled drug in ethanol along with Deionized distilled water (contains egg phosphatidylcholine) and deoxycholic acid. The suspension was sonicated in order to lessen the particle size [2]. An example is Saquinavir (anti-HIV inhibitor) showed enhanced oral absorption and increased concentration of drug in the brain when incorporated in a nanoemulsion

Although DOX is an effective chemotherapeutic, dosage in patients is limited clinically due to severe cardiac toxicity (weinstein et al .,2000 ; singal et al ., 2000) The clinical efficacy of DOX, particularly for long term treatment, is limited by the induction of hepatic and cardiac toxicities that are frequently lethal (saad et al .,2001).

Docetaxel is a member of taxan family (antineoplastic agents) which exert their cytotoxic effects on microtubules [1]. It inhibits the disassembly of tubulin leading to inhibited cell division and cell death [2, 3]. Docetaxel has demonstrated antitumor activity in the treatment of patients with various cancer types [3]. Due to insolubility of the drug in water, a mixture of ethanol and tween 80 (polysorbate 80) has been used in the commercial docetaxel formulation (taxoter®) to enhance the solubility [4]. There are issues associated with the medication, which are believed to be attributed to the formulation ingredients (ethanol/tween 80). These issues include hypersensitivity reactions, lower uptake by tumour tissue, and higher exposure of other body compartments to the drug [5, 6]. Meanwhile, alternate drug delivery systems have been invented to circumvent problems accompanied with docetaxel pharmacotherapy [7, 8] and make desirable alterations in the pharmacokinetic characteristics that could potentially enhance pharmacodynamic outcomes [9].

The technologic progress during the Industrial Revolution enhanced quality of life but also resulted in a human health burden. As in the case of asbestos with its decades of long latency that still remain, there are many legitimate concerns about the unknown human health consequences of nanomaterials. Nanotechnology, now at the leading edge of rapid development with many potential human health benefits, is perceived with apprehension for potential human health risks. Enhanced strength, durability, flexibility, performance, and inimitable physical properties associated with these materials has been exploited in a multitude of industries and treatment modalities including detection of tumors, targeted drug delivery, and prognostic visual monitoring

While chemotherapy and nanotechnology are both being utilized to treat cancer, they differentiate in the targeting procedure. Chemotherapy is a type of treatment for cancerous cells by cytotoxic drugs. Patients either receive monotherapy or combination therapy. The administration of these drugs can be orally or intravenously depending on the origin of the cancer. These chemotherapeutic agents work by interfering with the cell's genetic material, blocking the beneficial nutrients from the cell, triggering apoptosis and stopping the growth of blood vessels that supply the tumor. As a result, the increasingly divided cells are destroyed which leads to the disintegration of healthy cells alongside the cancer cells. Examples of healthy

Also, biotherapeutic therapy is similar to chemotherapy except that instead of delivering small molecular drugs (or metabolite ... etc.), biological agents such as DNA, small interfering RNA (siRNA), proteins, and peptides are delivered to tumor sites to induce apoptosis and cell death. In cancer, damaged DNA results in defect in protein expression causing deleterious effects. Cancer may be treated with DNA delivery by replacing the defective genes within cancer cells. Alternatively, cancer therapy via siRNA works by suppressing the protein expression of damaged genes. Protein and peptide therapy, on the other hand, operates by attacking specific cell mechanisms such as disrupting cell adhesion, interfering with angiogenesis, and/or blocking other

The efficient delivery of drugs and energy to tumors faces several difficulties and obstacles that need to be overcome for effective cancer treatment. Nanoparticles administrated through intravenous injections accumulate at a tumor site due to the enhanced permeability and retention (EPR) effect, but only a small quantity of the injected particles can actually “reach the tumor” (Su et al, 2016). The majority of the nanoparticles interact with “cancer cells at the periphery of a tumor” which presents a “physiological barrier” that prevents most of the injected particles from reaching the tumor (Su et al, 2016). In addition to this barrier, there is also another significant obstacle, “cancer-associated fibroblasts”, which can also

In this study, published in the scientific journal Advanced Materials, Quanyin Hu has created a better way to administer doxorubicin and TRAIL, two anticancer drugs. By using platelets, part of the blood that aids in clotting, to mask the foreign drugs from the body's defense system, these bioengineers caused the drugs to stay in the body for a longer amount of time when compared to the amount of time non-platelet covered anticancer drugs stayed in the body. The results of this experiment showed that platelet covered anticancer drugs stayed in the body longer than the same anticancer drugs surrounded by a nano-gel system. In this experiment, the dependent variable was the amount of time the anticancer drugs stayed in the body of a mouse.

Antiproliferative activity of Egyptian propolis nanoparticles/liposomes in cancer cell monolayers: multimode of action including apoptotsis and nitric oxide production

Conventional drug delivery systems (DDSs) are often accompanied by systemic side effects that mainly are attributed to their nonspecific bio-distribution and uncontrollable drug release characteristics. To overcome these limitations, advanced controlled DDSs have been developed to achieve the release of payloads at the target sites in a spatial controlled manner.

Colorectal cancer is one of the fatal diseases of this era with quite higher incidence rate. Due to a high fatality rate, health organizations and researchers are continuously looking for new and better management options. In this strive, nanotechnology served as a major and novel treatment methodology with betterment and more optimum outcomes. Work is carried out with respect to colo-rectal malignancies where nano-particles are either used as diagnostic tools or they serve as treatment tools for targeted drug delivery to the tumor cells. This all leads to more specific and sensitive drug delivery to site of action thus minimizing the dose associated and non-specific drug delivery side-effects. The following review article will address such efforts and their impact to reduce disease burden, thus improving future prospects of the disease.

Polymer drug conjugates as the name would suggest, are systems where drug molecules are chemically conjugated onto long chain polymers via covalent linkages. At the moment there over fourteen polymer-drug conjugates that have made it through the rigorous clinical evaluation, these are based on polyglutamic acid (PGA)-paclitaxel conjugates (CT-2303, OPAXIO®, initially known as Xyotax®) (Greco and Vicent 2009).

Cancer disease is one the most complicated fatal disease which scientists are looking for methods to either stop or cure this malady (Hook, Ptak, Farrell, Hinkal, Panaro and Grodzinski, 2010). Based on the cancer overlook disease, the cells are transformed and infected to cancer after a while and it starts to metastasize and proliferate (ibid). The cardinal issue is that how cancer may occur based on transformation of cells and genes. To illustrate that question, there are two factors that must be carried out together preemptory; one is cell replication and gene mutation and both of which results in programmed cell death, apoptosis. (Mansoori, Mohazzabi, McCormack, and Jabbari, 2007). Veraciously, apoptosis will likely to happen when the healthy cells could not be repaired and the errors stay put on the cells (ibid). The stimuli of this kind of cells behavior still debatable (Hook et al, 2010), yet there are some explanation that how it started by a virus infection which is not going to be discuss in this paper. Nevertheless, there are multifarious techniques for cancer treatment clinically, one of the significant promising methods to struggle inhibition or prognosis of cancer is nanotechnology.