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Nanotechnology in Stem Cell Regenerative Therapy and Its Applications
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Photon-absorbing carbon nitride (C3N4) nanosheets, biocompatible scaffolds treated on human bone marrow-derived MSCs, enhance differentiation for bone formation and help in bone regeneration and fracture curing. These activities get accelerated in the presence of red light. Further, this recuperates mechanical properties, controls drug release and biodegradability along with the bone repair after surgery, and results in bone density with less fibrous tissue development. The bone regeneration can be increased from combined human bone morphogenetic protein-2 along with hybrid hydroxyapatite-chitosan nanoparticles due to its osteoconductivity. Hydroxyapatite NPs3D scaffolds can be prepared by combining with gelatin that starts osteogenesis via autophagy activation, which leads to strong bone formation. The delivery of augmentation factors for bone repair is done using hMSCs, chitosan NPs, and fibrous scaffolds. For the bone formation of NRs and drug discharge of dexamethasone to support the osteogenic growth, nanocomposites produced from nanodiamonds and gelatin methacrylamide (GelMA) hydrogels can be utilised. The biomechanical strength of bone fractures increases with siRNA/NP hydrogel, and the healing capacity enhances through magnetofection (Pacelli et al. 2017).
Vaccine Adjuvants in Immunotoxicology
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Adjuvants containing the CpG dinucleotide directly stimulate B cells and dendritic cells. Thus, it promotes the production of cytokines and maturation/activation of antigen-presenting cells prior to an inflammation. CpG oligonucleotides are agonists of TLR found on the APCs (Klinman et al. 2009; Zimmermann, Dalpke, and Heeg 2008). These receptors are the source of the signals which trigger an immune response in the host when encountering a foreign antigen (Kindrachuk et al. 2009). They increase antigen-specific immune responses 5–500-fold (Klinman 2006). Nucleic acid vaccines (genetic vaccines) are based on the direct delivery of genetic material encoding the desired antigen to the host cell, and the creation of the immunity. They have some advantages such as better safety, the ability to specifically acquire immunity to an antigen, stimulating both B and T cell responses, relatively cheap cost and production (Zimmermann, Dalpke, and Heeg 2008; Gül and Dikmen-Yurdakök 2019). However, low stability and limited clinical application routes are some their disadvantages. On the other hand, areas of use of DNA and RNA vaccines are gradually increasing thanks to the production of various biomaterials with physical methods (such as electroporation, sonoporation and magnetofection) (Gül and Dikmen-Yurdakök 2019).
Imaging of Cell Trafficking and Cell Tissue Homing
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Fortunately, other strategies can be employed to not only overcome the problems associated with phagocytosis and to enhance the internalization of the cell label but also to label nonphagocytic cells. These methods make use of (1) external agents or the so-called forced-entry approaches such as transfection agents (Frank et al. 2002, 2003; Rudelius et al. 2003; Bulte et al. 2004; Bulte and Kraitchman 2004; Modo et al. 2005; Cova et al. 2013), electroporation (Walczak et al. 2005; Suzuki et al. 2007; Kim et al. 2011b), magnetofection (Scherer et al. 2002; Plank et al. 2003), or sonoporation (Mo et al. 2008); or (2) specific targeting strategies such as functionalization with specific ligands or cell-penetrating peptides and the use of specific cell membrane transporters (Bulte et al. 1999, 2004; Josephson et al. 1999; Ahrens et al. 2003; Doyle et al. 2007; Park et al. 2012). Examples of transfection agents are poly-l-lysine (Frank et al. 2003), cationic liposome (van den Bos et al. 2003), or protamine sulfate (Arbab et al. 2004), which form complexes with labeled nanoparticles and greatly improve their efficiency of endocytosis in cells that cannot avidly phagocytize. On the other hand, specific targeting can be achieved by using monocloncal antibodies (Weissleder et al. 1997; Bulte et al. 1999; Ahrens et al. 2003), specific receptor ligands such as transferrin (Qian et al. 2002), or specific trapping systems for 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) or 64Cu-PTSM (Koike et al. 1997; Adonai et al. 2002; Hofmann et al. 2005; Huang et al. 2008).
Advanced physical techniques for gene delivery based on membrane perforation
Published in Drug Delivery, 2018
Xiaofan Du, Jing Wang, Quan Zhou, Luwei Zhang, Sijia Wang, Zhenxi Zhang, Cuiping Yao
Magnetofection reagents play an important role in this process, which bear the magnetic force and carry the nucleic acids into cell. The nucleic acids combine with magnetofection reagents by electrostatic interaction or salt-induced colloid aggregation (Mehier-humbert & Guy, 2005; Arora et al., 2013). The magnetofection reagents, such as CoFe2O4, NiFe2O4 and MnFe2O4, exhibit superior transfection efficiency than other magnetic materials (Sun et al., 2000; Tomitaka et al., 2010). However, these reagents are highly toxic, which limits their application both in vivo and in vitro (George et al., 2011; Cho et al., 2012). Iron oxides (Fe3O4, γ-Fe2O3) are commonly employed as magnetofection reagent due to its advantages of low toxicity and biocompatibility (Arora et al., 2013; Das et al., 2015). Sohrabijam et al. coated the iron oxide nanoparticles with chitosan and used it for magnetofection. They demonstrated that transfection efficiency was significantly increased and the particles were nontoxic (Sohrabijam et al., 2017). Shi and his teammates devoted to research the nanocomposite of iron oxide nanocrystals which were used as magnetofection reagent and showed better magnetofection efficiency (Shi et al., 2015; Shi et al., 2016). In addition, carbon nanotubes (CNTs) are also used as magnetofection reagent to enhance the transfection efficiency of magnetoporation (Cai et al., 2005; Liu et al., 2012).
Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics
Published in Expert Opinion on Drug Delivery, 2019
Thomas Vangijzegem, Dimitri Stanicki, Sophie Laurent
Over the past decades, nanotechnologies have emerged as new powerful tools in numerous technological applications. These applications have prompted increasing interest from researchers, which have produced outstanding results in the development of nanodevices and nanomaterials of different kinds (metal, oxide, semiconductors…). Among various types of nanomaterials that were investigated, magnetic iron oxide nanoparticles (IONs) have been widely studied due to their intrinsic magnetic properties (i.e. superparamagnetism) enabling them to be used in several scientific fields such as electronics or environment [1–4]. In addition to these remarkable magnetic properties, IONs biocompatibility, stability, and ecofriendliness have made them the ideal platform for biomedical applications [5]. Firstly, in the medical imaging field, iron oxide nanoparticles are known for their use as contrast agents (CAs) for magnetic resonance imaging (MRI). Some formulations (Resovist®, Endorem®…) have been used previously in various clinical applications as T₂-weighted MRI CAs [6,7]. More recently, applications focusing on T₁-weighted MRI have been described and have given rise to promising results [8–12]. Besides their use for MRI, IONs also show great potential for applications with therapeutic purposes. They can be used to induce local heat enhancement when submitted to an alternative magnetic field, the so-called magnetic hyperthermia application. This property is particularly efficient for the elimination of cancer cells, which cannot survive in the temperature range of 42–49°C unlike healthy cells which are able to endure such temperatures [13]. Other biomedical applications like tissue repair, cell labelling and magnetofection have also been described [14].
Recent advances in metal nanoparticles in cancer therapy
Published in Journal of Drug Targeting, 2018
Ankush Sharma, Amit K. Goyal, Goutam Rath
Gene silencing is a phenomenon, where formation of specific translational product is blocked using selective and complimentary nucleotide called antisense. Antisense DNA [44,45] and RNA interference (RNAi) are small interfering RNA that plays a dominant and beneficial role in down regulation of specific gene expression in the tumour cells [46–50]. The potency or strength and duration of silencing response of siRNA into the mammalian cells after transfection depend on the methods of transfection, amount of siRNA delivered, and the potential of siRNA to supress the tumour genes. Metal NPs owing to its high positive surface charge, serve as an ideal carrier for negatively charged nucleotides (DNA and RNA). Metal NPs like AuNPs in addition, by targeting mRNA also interact with biomolecules of cell, induced greater cytotoxicity [51–53]. This increases the half-life of siRNA and decreases the dose required, gives protection from action of RNase by lipid coating, provides chemical stability of siRNA by coating with poly(β-aminoesters) and prevents common detachment from the vectors thereby overcoming the problems of insecurity about the delivery of therapeutic RNA and provides an efficient gene silencing strategy [54]. The endogenous mechanism involved in gene silencing is depicted in Figure 2. Magnemite NPs (Y-Fe2O3), also termed as magnetic reagent are used for efficient transfection (MagRET) gene silencer. It is prepared by coating magnemite core on the surface by lanthanide Ce(3/4+) cation. Further, magnemite core is bound to polyethylamine (PEI) through coordinative chemistry, enabled by the [CeL(n)](3/4+) cation/complex. In vivo toxicity was diminished by PEI oxidation. Success rate of the studies utilising mRNAs, microRNAs and long non-coding RNA (IncRNAs) was found to be increased up to 80–100% in a variety of cells [55]. The effect of superparamagnetic iron oxide as a core–shell NP altered with polycationic polymers (polyhexamethylene biguanide or branched polyethyleneimine) as siRNA transfection vehicles was observed against CHO-K1 and HeLa cell lines and was found to be superior compared to unmodified branched polyethyleneimine. The efficacy of superparamagnetic iron oxide NPs (SPIONs) is enhanced by magnetofection or external applied magnetic field (MF). These NPs were found to be least toxic than both unmodified polycationic branched PEI as well as polyhexamethylene biguanide. Generally, external MF does not change cell viability except in case of polyhexamethylene biguanide modified NPs where magnetofection promotes membrane damage [56]. Another example supports that anchoring of specific ligand improves transfection efficacy showing folic acid-conjugated AuNPs effectively transfer functional siRNA to silence RELA expression in prostate cancer. [57]. Both in vitro and in vivo efficacy of RNAi-AuNPs was found to be effective against C-MYC proto-oncogene. The combination of these chemical and biological approaches was found to be non-pathological, safe, self-tracking and universally valid for the delivery of therapeutic RNA [58]. Su et al. delivered siRNA to target C-MYC by designing a polyelectrolyte complex from AuNPs [58].