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

Abstract

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.

Magnetic Iron Oxide Nanoparticles for Multimodal Imaging and Therapy of Cancer

“…Genes are integrated into SPION, which protect the nucleic acids against enzymatic degradation and facilitate cellular internalization and endosomal release (Table 5). SPION are believed to be an excellent vehicle for siRNA delivery because they are biocompatible and target-functionalized [65]. Even hard-to-transfect cell lines can be delivered with plasmid DNA or siRNA by novel methods such as magnetofection, where SPION is subjected to oscillating magnetic fields that facilitate caveolae-mediated endocytosis of SPION and cargo nucleic acid [66,67].…”

Magnetic albumin immuno-nanospheres as an efficient gene delivery system for a potential use in lung cancer: preparation, in vitro targeting and biological effect analysis

“…These factors may be fine-tuned for nucleic acid delivery system, such as DNA [5] and siRNA [1]. Super-paramagnetic iron oxide nanoparticles (SPIONs) have been applied in biomedical research and clinical applications as an effective drug and gene delivery system, attribute to their specific magnetic properties, biocompatibility, stability in body fluids and non-immunogenicity [6]. The SPIONs aggregate only in the presence of a strong external magnetic field, however, after the period field is removed, the magnetization disappears [7].…”

Paradoxical Roles of Nanoparticles in Cancer Therapeutics and Carcinogenesis

“…Commonly used dose measures include concentration of the metal in the core, [179][180][181] particle mass, 182,183 or molarity. 157,159 When therapeutic ligands, such as ASO, 184 aptamers, 185 antibodies, 160 or targeting molecules like folate [186][187][188][189][190] are present, their concentration should also be considered. In many situations, the most appropriate dosing measure will be a combination of two or more measures, ensuring that all relevant components are accounted for.…”

“…145,153,192 For example, folate-conjugated NPs were taken up by tumors at a greater rate than surrounding tissue. 160,[186][187][188][189][190]200 The addition of an aptamer targeting prostate-specific membrane antigen (PSMA) to a doxorubicin-loaded SPION created a system that was cytotoxic only to PSMA-expressing cells. 185 Antibodies are also highly specific and can significantly increase accumulation within target tissues.…”

“…192 Antisense oligonucleotides (ASO), antibodies, or enzymes are often covalently linked to the outer surface of the particle. 150,189,[238][239][240] Lipophilic drugs like paclitaxel 160,215 or doxorubicin 185,[230][231][232][233] can be loaded into a surfactant layer between the SPION core and the polymer coating. Drugs can also be attached through links that are readily cleaved in response to changes in pH 230,231,233 or tissue-specific enzymes.…”