Superparamagnetic Nanoparticles and RNAi-Mediated Gene Silencing: Evolving Class of Cancer Diagnostics and Therapeutics

Hindawi Publishing Corporation Journal of Nanomaterials Volume 2012, Article ID 129107, 15 pages doi:10.1155/2012/129107 Review Article Superparamagnetic Nanoparticles and RNAi-Mediated Gene Silencing: Evolving Class of Cancer Diagnostics and Therapeutics Sanchareeka Dey and Tapas K. Maiti Biotechnology Department, Indian Institute of Technology, Kharagpur 721302, India Correspondence should be addressed to Tapas K. Maiti, Received 13 February 2012; Accepted 23 April 2012 Academic Editor: Haifeng Chen Copyright © 2012 S. Dey and T. K. Maiti. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The ever increasing death of patients affected by various types of fatal cancers is of concern worldwide. Curative attempts by radiation/chemotherapy and surgery are often a failure in the long run. Moreover, adverse side effects of such treatments burden the patients with painful survival at the last phase of their life. The failure of early diagnosis is one of the root causes of the problem. Intensive research activities are being pursued in reputed laboratories across the globe to find superior diagnostics and therapeutics. Over the last decade, a number of publications have highlighted RNA interference based silencing of cancer-related gene expression as a promising technology to tackle the aforesaid problems. Superparamagnetic iron oxide nanoparticles (SPIONs) are reported to be excellent vehicles for short-interfering RNA (siRNA). The SPION-siRNA conjugate is biocompatible, stable, and amenable to specific targeting and can cross the blood brain barrier. The issues related to their synthesis, surface properties, delivery, tracking, imaging in relevance to cancer diagnostic and therapeutic, and so forth demand an extensive review, and we have addressed these aspects in this paper. The future prospects of the technology have also been traced. 1. Introduction The number of patients suffering from various fatal types of cancers (lung, breast, prostate, etc.) has been increasing worldwide, irrespective of the countries that are developed or developing. Several nonspecific treatments include radiation therapy and chemotherapy. The treatment failure continues to be very high, and multidrug resistance is known. The adverse side effects of drugs and drug formulation vehicles are of serious concern [1]. Capecitabine, the oral prodrug for fluorouracil, for example, given to ovarian, prostate and pancreatic cancer patients develop systemic toxicity [2] including neutropenia, stomatitis, and so forth [3]. Similarly, breast cancer patients treated with anthracyclines and taxanes as well as antibody therapies (anti-HER2 drug herceptin) exhibit long-term cardiotoxicity. The blood brain barrier (BBB) is a major obstacle in the treatment of brain cancer through intravascular drug application because only a small fraction of the drug actually reaches tumor, and most local delivery methods bring neurotoxicity [4]. As a result of such healthcare complications in cancer patients receiving prolonged treatments, only palliative treatments are prescribed in many cases at the last phase of their survival. Targeted drug delivery systems (liposomes, micelles, polymer drug conjugates, etc.) have short comings of drug leakage in vivo, packaging limitations, reduced potency, and so forth. In the last decade, several exciting articles on RNAi have been published on their potential in suppressing oncogenes by silencing. The 20–30 nucleotides double-stranded small or micro-RNAs (siRNAs or miRNAs) cause natural posttranscriptional gene silencing in eukaryotic cells [5]. The delivery of siRNAs was experimented by conjugating with natural or synthetic polymers and using nanoparticles as a vehicle. The last one are the most important because of their nontoxicity, effectiveness due to large surface area, and ability to cross tight junction of endothelial cells in blood brain barrier. Superparamagnetic nanoparticles can act as agents for effective treatment of cancers, especially brain tumor. Superparamagnetic iron oxide nanoparticles (SPIONs) have interesting properties such as biocompatibility, stability in body fluids, nonimmunogenicity, and amenability to coating/conjugation for cell-specific targeting 2 and imaging/tracking. Overall, SPIONs could be designed into a multifunctional unit [6–8]. A recent article on the possibility of gene delivery by SPIONs in three-dimensional cell cultures underscores the amazing potential for this promising technology. In this paper, we review the usefulness of the versatile SPIONs with regard to their superiority as a vehicle for RNAi-mediated gene silencing. We present here their importance as an evolving new class of cancer diagnostics and therapeutics. 2. SPION Synthesis for Biomedical Application When the material dimension is reduced to nanoscale, the enhanced magnetic property is superparamagnetism. Ferro- or ferri-magnetic materials at sizes on the order of tens of nanometers become a single magnetic domain and maintain one large magnetic moment. At sufficiently high temperatures (i.e., blocking temperature TB), free rotation of the particle is however induced resulting in a loss of net magnetization (i.e., their magnetization appears to be in average zero, and they are said to be in the superparamagnetic state) in the absence of an external field [42]. SPIONs are the most commonly used superparamagnetic nanoparticles for biomedical applications (i.e., immunoassays, magnetic resonance imaging, magnetic cell separation, magnetic oligonucleotide and nucleic acid separation, drug delivery, etc.). There has been intense investigations by chemists and material scientists over the synthesis of SPIONs. SPIONs can be synthesized by either chemical or mechanical approaches. Chemical synthesis is however more suitable for the production of SPIONs of uniform size and composition [43]. A variety of synthetic processes have been adopted for the production of iron oxide nanoparticles ranging from the more conventional wet chemistry solutionbased methods to more fascinating techniques such as laser pyrolysis. The two most commonly employed methods for SPION synthesis for biomedical application include alkaline coprecipitation and microemulsion of Fe 2+ and Fe 3+ salts [44, 45]. 2.1. Coprecipitation. Coprecipitation is the most commonly followed synthetic route for SPION synthesis because it is the simplest and most efficient pathway [6, 45–47]. Iron salts are coprecipitated with a strong base under aqueous conditions to yield the core of the SPION [48]. During nanoparticle formation, conditions are optimized to yield a short nucleation event followed by a slower growth phase. The end product obtained has good monodispersity [49]. The SPION core has two fates. One is the direct conjugation of the core with surface coatings, w (...truncated)