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Lipid Nanocarriers for Oligonucleotide Delivery to the Brain
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Andreia F. Jorge, Santiago Grijalvo, Alberto Pais, Ramón Eritja
The application of these chimeras has proven to be also valuable in the treatment, diagnosis and imaging of brain tumours [82–85]. In this field, unique properties of aptamers have been exploited to detect tumour initiating cells by targeting the glycoprotein CD133 [69] or to distinguish glioblastoma multiforme (GBM) cells (U118-MG) from astroglial cells (SVGp12) [86]. Likewise, their high affinity to membrane receptors overexpressed in tumours may inhibit the signalling of, for instance, tyrosine kinase (Axl) receptors or growth factor receptor β(PDGFRβ), thus regulating tumour cell proliferation and migration [87, 88]. As an alternative, cell type-specific aptamers may be conjugated with therapeutic moieties, for example, siRNA, microRNA, anti-miR or antiproliferative agents, alone or coupled with nanoparticles for targeted delivery in tumour cells, thereby reducing unwanted off-target effects [89–92].
Natural enzymes used to convert feedstock to substrate
Published in Ruben Michael Ceballos, Bioethanol and Natural Resources, 2017
Apart from the cellulases and other cellulose-attacking enzymes, T. reesei harbors several genes that encode hemicellulases. This includes six ENs, four of which have been characterized and belong to EN families GH10 (XYNIII), GH11 (XYNI, XYNII), and GH30 (XYNIV) (Tenkanen et al., 1992; Torronen et al., 1992; Xu et al., 1998) as well as three candidate ENs (i.e., XYNV or gene 112392, gene 41248, and gene 69276) (Metz et al., 2011; The Regents of the University of California, 2015). There are also one MAN (i.e., MANI) (Stålbrand et al., 1995), one candidate AXL (gene 69944); one candidate β-1,3-mannanase (gene 71554); six candidate MND enzymes (genes: 5836, 69245, 59689, 57857, 62166, and 71554) (The Regents of the University of California, 2015); one characterized AXE (i.e., AXEI); and three putative AXEs (i.e., AXEII, gene 70021, and gene 54219) (Margolles-Clark et al., 1996d; Foreman et al., 2003; Herpoel-Gimbert et al., 2008; The Regents of the University of California, 2015).
Aptamers as Tools for Targeted Drug Delivery
Published in Rakesh N. Veedu, Aptamers, 2017
MicroRNAs (miRNAs) are short noncoding RNAs that can induce gene regulation either by inhibiting translation or by degrading complementary messenger RNA. Jan-H. Rohde et al. [62] have reported a method to deliver miRNA and miR-126 to endothelial and breast cancer cells. miR-126 is essential for vasculature growth but at the same time is implicated in the development of various cancers. The authors tested three different strategies for delivering miR-26 to endothelial cells via a transferrin receptor-targeting aptamer. One of the strategies was by conjugating pre-miR-126 to the aptamer, which resulted in the delivery of functional miR-126. On delivery to the target cells, the pre-miR-126 was endogenously processed, followed by the inhibition of the target gene vascular cell adhesion molecule-1 (VCAM-1). The aptamer–miRNA chimera resulted in endothelial cell sprouting and inhibited tumor cell proliferation and recruitment of endothelial cells [62]. Two nuclease-resistant aptamers, GL21.T and Gint4.T-targeting receptor tyrosine kinases Axl and PDGFRβ, respectively, were used to selectively target and deliver tumor suppressor antimiR-222 [14]. AntimiRs antagonize the endogenous miRNA and lead to increased levels of microRNA target proteins. A stick-annealing approach was used to form a highly stable bridge duplex between the aptamer and the antimiR. The aptamer–anti-miR complexes were rapidly internalized into the target cells by receptor-mediated pathway, and the results indicate that the cells treated with the anti-miR–aptamer complex expressed receptor-dependent selective downregulation of respective miRNA levels [14].
The emergence of nanoporous materials in lung cancer therapy
Published in Science and Technology of Advanced Materials, 2022
Deepika Radhakrishnan, Shan Mohanan, Goeun Choi, Jin-Ho Choy, Steffi Tiburcius, Hoang Trung Trinh, Shankar Bolan, Nikki Verrills, Pradeep Tanwar, Ajay Karakoti, Ajayan Vinu
Using short interference RNAs (siRNA), targeted therapy for various pathways has been studied with different nanoparticles such as polymers, inorganic and organic nanoparticles. Challenges, including poor conjugation, reduced stability, and ineffective release to the cytoplasm, must be overcome before a successful translation of siRNA-based nanomedicines. To overcome these challenges, Suresh et al. developed gelatin nanoparticles functionalised with antibodies [287]. Gelatin is another natural molecule made up of collagen and is used for reducing systemic immune response during drug delivery. Gelatin was synthesised with two-step desolvation process with glutaraldehyde as a crosslinker. To reduce the toxicity of the gelatin arising from the aldehyde groups on gelatin, excess glutaraldehyde was quenched with tris glycine. The modified gelatin was functionalised with cetuximab (anti-AXL antibody) by EDC/sulfo-NHS chemistry. AXL (Ark or UFO) is a member of TAM family of receptor tyrosine kinase, which is highly expressed in cancers. The gene silencing efficacy was analysed by western blotting in EGFR mutant H820 cells. The H820 cells were incubated with the gelatin-antibody for 72 hours, and it was estimated that >25 nM of transfected-siRNA was required for ~70% knock-down of AXL protein. Thus, high transfection efficiency with minimal toxicity can be achieved by utilizing porous gelatin hydrogels. Similar studies are reported in other cancers such as breast and colon cancers [288].