{"id":53,"date":"2019-11-28T01:45:13","date_gmt":"2019-11-28T06:45:13","guid":{"rendered":"https:\/\/www.cd-bioparticles.com\/blog\/?p=53"},"modified":"2019-11-28T01:45:13","modified_gmt":"2019-11-28T06:45:13","slug":"application-of-inorganic-nanomaterials-in-gene-therapy","status":"publish","type":"post","link":"https:\/\/www.cd-bioparticles.com\/blog\/applications\/application-of-inorganic-nanomaterials-in-gene-therapy\/","title":{"rendered":"Application of Inorganic Nanomaterials in Gene Therapy"},"content":{"rendered":"\n<div class=\"wp-block-image\"><figure class=\"aligncenter\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"683\" src=\"\/blog\/wp-content\/uploads\/2019\/11\/Application-of-Inorganic-Nanomaterials-in-Gene-Therapy-1-1024x683.jpg\" alt=\"\" class=\"wp-image-54\" srcset=\"\/blog\/wp-content\/uploads\/2019\/11\/Application-of-Inorganic-Nanomaterials-in-Gene-Therapy-1-1024x683.jpg 1024w, \/blog\/wp-content\/uploads\/2019\/11\/Application-of-Inorganic-Nanomaterials-in-Gene-Therapy-1-300x200.jpg 300w, \/blog\/wp-content\/uploads\/2019\/11\/Application-of-Inorganic-Nanomaterials-in-Gene-Therapy-1-768x512.jpg 768w, \/blog\/wp-content\/uploads\/2019\/11\/Application-of-Inorganic-Nanomaterials-in-Gene-Therapy-1-120x80.jpg 120w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure><\/div>\n\n\n\n<p>Gene therapy is the introduction of an exogenous normal\ngene or a therapeutic gene into a target tissue or target cell by a vector or\nother means, and is appropriately expressed to treat a disease. The key to gene\ntherapy is to obtain efficient and safe gene delivery vectors. Vectors for\ndelivering genes are generally classified into viral vectors and non-viral\nvectors. Viral vectors are the most widely used gene delivery vectors,\nincluding retroviruses, adenoviruses, adeno-associated viruses, and\nlentiviruses. The biggest advantage of viral vector is the high transfection\nrate, but there are also many shortcomings, such as difficulty in preparation\nof virus, limitation of the size of foreign DNA loaded, cytotoxicity,\nimmunogenicity, and carcinogenicity. The originality and tumorigenicity have\nnot yet been completely solved, and these disadvantages have greatly limited\nthe clinical application of the viral-type carrier.<\/p>\n\n\n\n<p>At present, non-viral vectors do not reach the extremely\nhigh transfection efficiency of viral vectors, but non-viral vectors make up\nfor the defects of viral vectors, with advantages like high safety, low\nimmunogenicity, simple preparation, tight binding to DNA, no limitation of DNA\nfragment size, and the ability to deliver plasmid DNA to target cells by\ntargeted modification, which makes gene therapy possible in clinical\napplications. Nano-gene delivery technology uses nanoparticles as vectors, and\nencapsulates DNA, RNA, etc. in nanoparticles or adsorbs on their surfaces, and\ncouples specific targeting molecules (monoclonal antibodies, etc.) on the\nsurface of the particles. It utilizes the interaction between the target\nmolecules on the nanoparticles and the cell surface-specific receptor to target\naimed cells. Under the action of lysosome, the nanoparticle is degraded to\nrelease the therapeutic gene, and the targeted gene therapy is realized. It can\nprotect nucleic acid from enzymatic degradation, increase the amount of nucleic\nacid into the cell, enhance its stability in the cell, prolong the sustained\nexpression time of the gene, help to improve the efficiency of cell\ntransfection, and possibly achieve localization targeting delivery.<\/p>\n\n\n\n<p><strong>Inorganic Nanomaterial<\/strong><\/p>\n\n\n\n<p><strong>1. Hydroxyapatite nanoparticles<\/strong><\/p>\n\n\n\n<p>Hydroxyapatite (HA) is one of the components of human bones\nand teeth and has good biology activity, chemical stability, and\nbiocompatibility, which is a common biological material for clinical bone\ndefect repair. The particle size of HA nanoparticles ranges from 1 to 100 nm,\nand has the common characteristics of general nanomaterials such as macroscopic\nquantum effect, small size effect, specific surface effect and interface\neffect. HA is a highly efficient adsorbent material widely used for the\nseparation and purification of proteins and nucleic acids. The preparation of\nHA nanoparticles is mainly liquid phase synthesis, including hydrothermal\nreaction, precipitation, sol-gel and microemulsion methods. Compared with silica\nnanoparticles, HA has better biofilm compatibility, strong nucleic acid\nadsorption capacity, and can be designed according to needs. Further discussion\nof its transduction mechanism, toxicology and preparation process, and improvement\nof its transduction rate are the key to promoting the application of HA\nnanoparticles in gene therapy.<\/p>\n\n\n\n<p><strong>2. Gold nanoparticles<\/strong><\/p>\n\n\n\n<p>Gold nanoparticles (AuNPs) are usually 10-20 nm in diameter\nand are generally used in the form of gold sols, also known as colloidal gold.\nIt is a new material with many biological functions, good biocompatibility and\nno obvious toxicity to cells. It has a variety of synthetic methods for\npreparing <a href=\"https:\/\/www.cd-bioparticles.com\/product\/gold-nanorods-list-165.html\">gold nanoparticles<\/a> with\nparticle sizes ranging from a few nanometers to hundreds of nanometers. AuNP\nhas a strong adsorption effect on many biomacromolecules and does not denature\nbiological macromolecules. It has been reported that AuNP transports DNA to the\nnucleus eight times more efficiently than PEI and has been successfully used in\ncancer therapy. AuNP crosses the cell membrane either by endocytosis or by\ndirect infiltration into target cells, which may have cytotoxic effects during\nthis process.<\/p>\n\n\n\n<p>Therefore, in the design and preparation of nanogold, the\nbalance between achieving an effective control of the amount of nanoparticles\npassing through the cell membrane and its potential toxicity is the key to the\nstudy. Au55 clusters are effective in interacting with DNA. This effect is\nrelated to the particle size, and the cluster of gold particles with small\nparticle size can be inserted. The surface of the gold can be covalently linked\nto the thiol, so the DNA can be immobilized on the AuNP after thiolation. An\nAuNP can bind up to several hundred DNA molecules. Despite the broad\napplication prospects of AuNP vectors, the cytotoxicity of AuNP still limits\nits biological applications.<\/p>\n\n\n\n<p><strong>3. Carbon nanotubes<\/strong><\/p>\n\n\n\n<p>Carbon nanotubes (CNTs) have typical layered hollow\nstructure features, and their body part is composed of six sides. The carbon\nring microstructure unit has a polygonal structure composed of a\npentagon-shaped carbon ring. CNTs can be classified into single-walled carbon\nnanotubes (SWNTs) and multiwalled carbon nanotubes (MWNTs) according to their\nstructure and dimension. The strong acid-treated MWNT was modified with PEI to\nreact acetic anhydride and succinic anhydride with the amino group of PEI on\nthe surface of MWNT to obtain MWNT with uncharged and negatively charged surface,\nrespectively. It was introduced into FRO cells (thyroid cancer cell line) and\nKB cells (epidermal cancer cell line) <em>in vitro<\/em>, indicating that its biocompatibility\nis related to its surface charge. The CNTs used as gene carriers need to be\nfunctionalized and modified, mainly because unmodified CNTs are insoluble in\nbody fluids and are toxic.<\/p>\n\n\n\n<p><strong>4. Quantum dots<\/strong><\/p>\n\n\n\n<p><a href=\"https:\/\/www.cd-bioparticles.com\/product\/quantum-dots-list-169.html\">Quantum dots<\/a> (QDs) are\nparticles with a particle size of a few nanometers and consist of II~IV or I~V\nsemiconductors, such as CdSe, ZnSe, GaAs, InAs, and the like. QD is inherently\ntoxic due to the presence of surface cations (such as Cd2+) and the formation\nof photoradicals. Surface modification can reduce QD toxicity. Combining\namphiphilic polymers with QD produces a novel gene delivery system that is\nsuperior to liposomes in serum-free and complete cell culture media and is less\ntoxic than PEI in gene silencing experiments. Due to the intrinsic emission of\nfluorescence and excellent optical properties, QD is widely used for siRNA\ndelivery and <em>in vitro\n<\/em>and <em>in vivo<\/em>\nimaging. L-arginine-modified functionalized CdSe\/ZnSe QD is an effective\nconfrontation against nucleic acid degradation, which successfully delivers\nsiRNA, and simultaneously acts as a fluorescent probe for real-time <em>in vivo<\/em> image\ntracking. At present, the research on QD shows that the transfection rate is\nlow and has certain toxicity, but its excellent optical properties of intrinsic\nemission fluorescence make QD as a gene carrier with certain development\nprospects.<\/p>\n\n\n\n<p><strong>5. Silica nanoparticles<\/strong><\/p>\n\n\n\n<p>The synthesis of SiO<sub>2<\/sub> is simple and the controllability is strong, and its outstanding advantages are that the surface modification range is wide, and the wide variety of silane reagents provides good conditions for the functionalization of SiO<sub>2<\/sub>. Taking advantage of the phenomenon that DNA is specifically adsorbed on the surface of SiO<sub>2<\/sub> under high salt conditions, SiO<sub>2<\/sub> nanoparticles without any functionalization can be used as an effective DNA extraction material. The positively modified SiO<sub>2<\/sub> particles (aminosilane, divalent cations, etc.) on the surface can effectively protect genetic material from enzymatic degradation, and have a good gene transfection effect <em>in vivo<\/em> and <em>in vitro<\/em>. Antisense oligonucleotide-containing aminated SiO<sub>2<\/sub> nanoparticles, with an average particle size of 25 nm, can protect antisense oligonucleotides from being decomposed by nucleases, improve transfection rate, prevent cancer cell differentiation and proliferation, and have better biocompatibility. <\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-style-default is-layout-flow wp-block-quote-is-layout-flow\"><p>References: <br> 1. Park TG, JeongJ H,Kim S W. Current status of polymeric gene delivery systems. <em>Adv Drug Del Rev<\/em>, 2006, 58:467-486.<br> 2. Luo D, Saltzman W M. Synthetic DNA delivery systems. <em>Nat Biotechnol<\/em>, 2000, 18: 33-37.<br> 3. Lehrman S. Virus treatment questioned after gene therapy death, <em>Nature<\/em>.1999, 401: 517-518.<br> 4. Marshall E. Gene therapy death prompts review of adenovirus vector, <em>Science<\/em>, 1999, 286: 2244-2245. <br> 5. Guo X, Huang L. Recent advances in nonviral vectors for gene delivery. <em>Accounts Chem Res<\/em>, 2012, 45: 971-979.<br> 6. Sandhu K K, McIntosh C M,Simard J M,et al. Gold nanoparticle mediated transfection of mammalian cells. <em>Bio-conjugate Chem<\/em>, 2001. 13: 3-6. .<br> 7. JainP K, El-SayedI H,El-Sayed M A. Au nanoparticles target cancer. <em>Nano Today<\/em>, 2007, 2: 18-29.<br> 8. Shukla R, Bansal V. Chaudhary M,et al. Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. <em>Langmuir<\/em>. 2005, 21: 10644- 10654.<br> 9. Sofou S, Sgouros G. Antibody- targeted liposomes in cancer therapy and imaging. <em>Expert Opin Drug Del<\/em>, 2008, 5:189-204.<br> 10. Liu Y, Meyer Zaika W, FranzkaS, et al. Gold-cluster degradation by the transition of B DNA into A-DNA and the formation of nanowires. <em>Angew Chem Int Ed<\/em>, 2003, 42: 2853-2857.<br> 11. LeroueilP R, Hong s, Mecke A. et al. Nanoparticle interaction with biological membranes: does nanotechnology present a janus face? <em>Accounts Chem Res<\/em>, 2007, 40: 335-342.<br> 12. Shen M, WangS H,Shi X,et al. Polyethyleneimine -mediated functionalization of multiwalled carbon nanotubes: synthesis, characterization, and in vitro toxicity assay. J <em>Phys Chem C<\/em>, 2009, 113: 3150-3156.<br> 13. Qi L, Gao X. Quantum dot amphipol nanocomplex for intracellular delivery and real time imaging of siRNA. <em>ACS Nano<\/em>,2008, 2: 1403-1410.<br> 14. Michalet X, PinaudF F,Bentolila L A,et al. Quantum dots for live cells, in vivo imaging, and diagnostics.<em> Science<\/em>, 2005,307: 538-544.<br> 15. LiJ M, Zhao MX. Su H, et al. Multifunctional quantum- dot-based siRNA delivery for HVP18 E6 gene silence and intracellular imaging. <em>Biomaterials<\/em>, 2011,32: 7978-7987.<br> 16. Kneuer C, Sameti M,Haltner E G,et al. Silica nanoparticles modifed with aminosilanes as carriers for plasmid DNA. <em>Int J Pharm<\/em>, 2000, 196: 257-261. .<br> PengJ, He X, Wang K, et al. An antisense oligonucleotide carrier based on amino silica nanoparticles for antisense inhibition of cancer cells. <em>Nanomed Nanotechnol Biol Med<\/em>, 2006,2: 113-120. <\/p><\/blockquote>\n","protected":false},"excerpt":{"rendered":"<p>Gene therapy is the introduction of an exogenous normal gene or a therapeutic gene into a target tissue or target<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[9,8,5,10,11],"class_list":["post-53","post","type-post","status-publish","format-standard","hentry","category-applications","tag-carbon-nanotubes","tag-gold-nanoparticles","tag-nanoparticles","tag-quantum-dots","tag-silica-nanoparticles"],"_links":{"self":[{"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/posts\/53","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/comments?post=53"}],"version-history":[{"count":4,"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/posts\/53\/revisions"}],"predecessor-version":[{"id":58,"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/posts\/53\/revisions\/58"}],"wp:attachment":[{"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/media?parent=53"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/categories?post=53"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.cd-bioparticles.com\/blog\/wp-json\/wp\/v2\/tags?post=53"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}