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Graphene Applications in Biology and Medicine
Published in Klaus D. Sattler, st Century Nanoscience – A Handbook, 2020
In order to increase the therapeutic efficacy and to reduce the side effects related to the administration of the drug, various systems based on graphene have been used: graphene sheets conjugated with a peptide (chlorotoxin) (CTX-GO) have been prepared and used for the transport of DOX for non-covalent CTX-GO-DOX interactions. Chlorotoxin or CTX is a peptide of 36 amino acids that is found, together with other neurotoxins, in the venom of the yellow scorpion (Leiurus quinquestriatus), a scorpion of the Buthidae family. This toxin blocks the chlorine-dependent ion channels, acting as a neurotoxin: this fact, together with the fact that chlorotoxin exceeds the blood–brain barrier (BEE) and binds to the tumor cells of the gliomas, has suggested that the same can be usefully used in the treatment of the same tumor forms. The release of DOX proved to be pH dependent and showed good diffusion properties. In a subsequent study, Depan et al. used folic acid conjugated with chitosan to modify nano-GO later used to transport DOX; in a recent work, nano-GO functionalized with dihydroartemisinin (DHA) and transferrin was used in the development of a controlled-release chemotherapeutic drug: in this case, a significant increase in tumor specificity was observed. In addition, hyaluronic acid (HA) was used for the modification of nano-graphene, aimed at the transport of an anti-tumor drug by means of endocytosis-mediated HA receptors.
Hybrid Nanosystems
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Pablo Vicente Torres-Ortega, Laura Saludas, Jon Eneko Idoyaga, Carlos Rodríguez-Nogales, Elisa Garbayo, María José Blanco-Prieto
Many studies have also focused on exploring the potential of HNs formed by an inorganic core coated with functional molecules in brain cancer. Iron oxide NPs (IONPs) and quantum dots (QDs) can be found within this type of nanosystem. In most cases, these formulations led to the development of promising diagnostic tools for application in brain tumours. In this regard, Tomanek et al. determined the accumulation of a targeted contrast agent in tumour vessels using a GBM mouse model. In this case, SPIO coated with dextran and functionalised with anti-insulin-like-growth-factor binding protein 7 single-domain antibody was synthesised. For the in vivo fluorescence follow up study, a near infrared marker (Cy5.5) was also attached to the formulation, and a GBM-targeted contrast agent was obtained. The formulation was administered to U87MGdEGFRvIII tumour-bearing nude mice, leading to HN accumulation in the tumour, as demonstrated by in vivo imaging techniques and magnetic resonance imaging (MRI). These results confirmed that HNs were able to selectively bind to abnormal vessels within a glioblastoma [14]. Nevertheless, this approach needs to be further explored in order to find the optimal pulse sequence for the superparamagnetic-based contrast agent of GBM MRI at the high field. Similarly, Veiseh et al. synthesised a diagnostic nanoprobe consisting of an IONP coated with a biocompatible polymer-based layer of PEG-grafted chitosan, chlorotoxin and near infrared fluorophore (Cy5.5). The MRI capacity of the nanoprobe was tested in transgenic ND2:SmoA1 mice generated on a C57BL/6 background, showing an enhanced contrast on tumour areas of the brain due to the accumulation of the nanoprobe on damaged tissues compared to tumour-free areas of the brain. These results evidenced a high chlorotoxin tumour-targeting capacity and selectivity. Furthermore, the safe BBB-crossing ability of the nanoprobe was also studied, showing an innocuous toxicity profile [15]. Chlorotoxin-labelled magnetic nanovectors were also prepared by Kievit et al. for targeted gene delivery to glioma and for diagnostic purposes [16]. The developed nanovector consisted of an IONP core coated with a copolymer of PEG, chitosan and polyethylenimine. Green fluorescent protein (GFP) encoding DNA and chlorotoxin was attached to this nanovector for optical monitoring of the gene expression and for NP targeting, respectively. In vivo gene delivery was tested on mice bearing C6 xenograft flank tumours. MRI showed the accumulation of nanovectors in the tumour site, whereas the increase in GFP expression on the tumour cells revealed an enhanced nanovector uptake into the cancer cells due to the chlorotoxin [16]. This study offers an interesting point of view on glioma diagnosis. However, further studies should consider the use of an autograft glioma model to evaluate the therapeutic efficacy of the formulation on a clinically relevant glioma model and to prove safety regarding the BBB. The combination of this imaging tool with a chemotherapeutic agent should also be considered for the development of a theragnostic platform.
Gold nanoparticles: a novel paradigm for targeted drug delivery
Published in Inorganic and Nano-Metal Chemistry, 2023
Kamalavarshini S, Ranjani S, Hemalatha S
Metals, semiconductors, carbon dots, carbon nanotubes, oxides all compose of inorganic nanoparticles are each of these are separately and keenly explored currently for oncologic diagnosis and therapeutic goals (Figure 2). Recently, Nanodiamonds have greatly contributed to stem cell therapy and as novel drug delivery vectors. Magnetic and catalytic properties of iron oxide nanoparticles have contributed toward accomplishing their superiority in nanomaterial synthesis for disease medications. Sun et al. conducted a research on IONPs conjugated with methotrexate, a chemo-drug along with chlorotoxin ligand during MRI studies revealed their toxicity in tumor cells.[43] SIONPs capped along bovine serum albumin were utilized as contrast agents for pancreatic cancer imaging and diagnosis.[44] Nontoxicity and biocompatible nature of zinc oxide nanoparticle favors their utility as potential candidates for wide range of biomedical applications. cancer cells death produced by cell cytotoxicity and ROS generation was initiated by application of ZnONPs.[45] In 2016, Experiments carried out demonstrated that conjugating siRNA and irinotecan for inhibiting growth of breast cancer cells by Akt kinase activation and degradation initiated by Mdm2 regulation were successful, added advantages of tumor growth inhibition and mediation of apoptosis were observed. Silver nanoparticles have unique plasmonic structure that promotes absorption and light dispersion, dual purpose is served by utilizing these NPs as they account for tumor cells elimination by increasing thermal conditions and imagining of tumor regions are also possible. In 2014 Boca et al.[46] conducted an experiment in which chitosan mediated silver nanoparticle labeled with a p-aminothiophenol were used to target cancer cell treatment for producing therapeutic response by irradiation with a NIR laser in resonance with AgNPs plasmonic band.