Recent advances of metal-based nanoparticles in nucleic acid delivery for therapeutic applications

Abstract

Recent efforts in designing nanomaterials to deliver potential therapeutics to the targeted site are overwhelming and palpable. Engineering nanomaterials to deliver biological molecules to exert desirable physiological changes, with minimized side effects and optimal dose, has revolutionized the next-generation therapy for several diseases. The rapid progress of nucleic acids as biopharmaceutics is going to alter the traditional pharmaceutics practices in modern medicine. However, enzymatic instability, large size, dense negative charge (hydrophilic for cell uptake), and unintentional adverse biological responses—such as prolongation of the blood coagulation and immune system activation—hamper the potential use of nucleic acids for therapeutic purposes. Moreover, the safe delivery of nucleic acids into the clinical setting is an uphill task, and several efforts are being put forward to deliver them to targeted cells. Advances in Metal-based NanoParticles (MNPs) are drawing attention due to the unique properties offered by them for drug delivery, such as large surface-area-to-volume ratio for surface modification, increased therapeutic index of drugs through site-specific delivery, increased stability, enhanced half-life of the drug in circulation, and efficient biodistribution to the desired targeted site. Here, the potential of nanoparticles delivery systems for the delivery of nucleic acids, specially MNPs, and their ability and advantages over other nano delivery systems are reviewed. Graphical Abstract

DNA-Based Nonviral Gene Therapy─Challenging but Promising

“…Due to their low toxicity, low production cost and potential for direct targeting using external magnets, iron oxide nanoparticles (IONPs) have attracted great interest in gene delivery applications and the functionalization of their surfaces is one of the key features for developing these materials as drug and gene carriers. 131 Nowadays, IONPs have become one of the most well-studied nanomaterials in cancer therapy. Shakil et al 133 successfully used IONPs as therapeutic diagnostic agents for gene therapy in breast carcinoma.…”

“…Among metal materials, magnetic materials have also been the subject of significant research. Due to their low toxicity, low production cost and potential for direct targeting using external magnets, iron oxide nanoparticles (IONPs) have attracted great interest in gene delivery applications and the functionalization of their surfaces is one of the key features for developing these materials as drug and gene carriers . Nowadays, IONPs have become one of the most well-studied nanomaterials in cancer therapy.…”

“…In addition, silver nanoparticles (AgNPs) have been extensively studied for their potential antimicrobial properties (Figure 6B), but their application has been limited by genotoxicity and nonspecific biotoxicity to mammalian cells. 131,132 Among metal materials, magnetic materials have also been the subject of significant research. Due to their low toxicity, low production cost and potential for direct targeting using external magnets, iron oxide nanoparticles (IONPs) have attracted great interest in gene delivery applications and the functionalization of their surfaces is one of the key features for developing these materials as drug and gene carriers.…”

“…MNPs are a unique class of nanocarriers with well-defined structures, tunable pore sizes, ultrahigh surface areas and chemical functionalization that can be used not only for delivery systems but also for other applications such as diagnostics. 131 However, MNPs are still in the early stages of development that need improvement, and there are still large gaps in delivering DNA therapeutic.…”

Nanoparticles as Drug Delivery Systems: A Review of the Implication of Nanoparticles’ Physicochemical Properties on Responses in Biological Systems

“…As such, many of these nanoparticles have already been approved by the Federal Drug Administration in the United States for clinical use ( Table 1 ). Nanoparticles that are popularly used in research for therapeutic purposes include encapsulated mRNA (siRNA) or DNA (in gene therapy), inorganic metal and metal complexes, or chemotherapeutic agents with pharmacologic abilities [ 33 , 34 ]. However, some of these nanoparticles do not easily traverse the cell membrane, requiring delivery systems to alleviate such difficulties.…”