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Radiochemistry for Preclinical Imaging Studies
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
This protocol typically applies to radiolabeling peptides with fluorine-18. [18F]N-succinimidyl fluoro-4-benzoate ([18F]SFB) is a well-known prosthetic group with an activated ester function to primarily target lysine side chains (Vaidyanathan and Zalutsky 1992). The selectivity of the prelabeled reagent has been much improved with the use of [18F]fluoro-4-benzaldehyde ([18F]FBA) (Poethko et al. 2004). However, this approach required the coupling of an aminooxy reactive group to the vector molecule. In consequence, this labeling method allows for high chemoselectivity through the orthogonal reactant pair of an aldehyde and an aminooxy group. Although the aromatic ring introduces some lipophilicity into the vector, the aromatic fluorine-18 C-F bond is sufficiently stable as demonstrated in numerous preclinical studies. Figure 16.17 exemplifies the radiochemistry for the preparation of [18F]fluciclatide, an RGD (arginylglycylaspartic acid) receptor–binding oncology marker that has already reached clinical trials (Pettitt et al. 2010). The labeling reagent [18F]FBA can be obtained from the trifluoromethanesulfonate (triflate) precursor 5 after purification by a solid phase extraction cartridge (SPE). Following the coupling step with the aminooxy peptide precursor, [18F]fluciclatide is purified by another SPE step. The full radiochemical preparation has been implemented on the FASTlab module and provides the tracer with a non-decay-corrected radiochemical yield of 20% (Pettitt et al. 2010).
Intraoperative Infrared Optical Imaging in Neurosurgery
Published in Yu Chen, Babak Kateb, Neurophotonics and Brain Mapping, 2017
Michael E. Wolf, Richard P. Menger, Osama Ahmed, Shahdad Sherkat, Babak Kateb
Arginylglycylaspartic acid (RGD) is a tripeptide composed of l-arginine, glycine, and l-aspartic acid that exhibits specific adhesion to αvβ3 integrins. These αvβ3 integrins are overexpressed in many tumor cell lines thus the use of RGD ligands may increase the internalization of fluorophores into tumor cells (Ye and Chen 2011). RGD and its associated conjugates are diminutive in size, giving them easier access to tumor tissues. These compounds also pose minimal risk of immune response, and their synthesis is inexpensive and simple (Wang et al. 2013). RGD may be decorated with imaging moieties while maintaining biological interaction with specific receptors.
Hepatocyte Differentiation from iPSCs or MSCs in Decellularized Liver Scaffold: Cell–ECM Adhesion, Spatial Distribution, and Hepatocyte Maturation Profile
Published in Organogenesis, 2022
Radiana Dhewayani Antarianto, Adrian Pragiwaksana, Wahyunia Likhayati Septiana, Nuzli Fahdia Mazfufah, Ameer Mahmood
This study in in vitro hepatocyte differentiation protocol is one continuous set of iPSC differentiation in decellularized liver scaffold for 21 days with periodic hepatocyte induction medium change without perfusion pump machine. Previous studies showed higher hepatocyte differentiation efficiency by dividing each differentiation step, thus providing differences of culture conditions (enriched microenvironment), which set the stage for developmental milestones.31,32 Further selections of iPSC colony size, separation of undifferentiated iPSCs at the time of differentiation step, monitor iPSCs density before and after endoderm induction or further differentiation step.33–36 The microchip fluidic PMDS platform has been shown to recapitulate liver morphology and various liver functions for 4–6 weeks in vitro.37,38 In addition, previous study suggests arginylglycylaspartic acid (RGD) incorporated into scaffold designs to support cell attachment.39 Other approach is to involve these various techniques, including 3D co-culture with non-parenchymal cells (endothelial cells and mesenchymal cells) in the form of organoid.40,41
An update on liposomes in drug delivery: a patent review (2014-2018)
Published in Expert Opinion on Therapeutic Patents, 2019
Mazen M. El-Hammadi, José L. Arias
Combined targeting is expected to enhance the effectiveness and selectivity of drug delivery to the targeted cells. In one patent, PEGylated LPs were surface functionalized with α-helical amphipathic 30-amino acid peptide, with the major repeat unit Glu-Ala-Leu-Ala (GALA peptide), for targeting lung endothelium [75]. Compared to LPs surface coated with GALA, PEGylated LPs surface functionalized with GALA showed a higher cellular uptake regardless of the density of the targeting ligand. Consistent with in vitro findings, a better accumulation of PEGylated LPs in the lung was observed after intravenous administration to mice [76]. In another patent, Topotecan (an anti-human epidermal growth receptor 2 molecule, which is a Camptothecin chemotherapeutic agent) incorporated to PEGylated LPs designed to target tumors of the central nervous system showed significant cellular uptake which was 50 to 300 times higher than that of non-targeted LPs [77]. Furthermore, arginylglycylaspartic acid peptide-modified PEGylated LPs were formulated and loaded with Ergosterol, a triterpene constituent of Taiwan’s unique Antrodia camphorata formulation with antitumor activity, and Cisplatin [48]. The sequences of arginine-glycine-aspartic acid in the arginylglycylaspartic peptide can specifically bind to integrins containing αV subunits with high affinity. Thus, the LPs produced with an average size of about 150 nm and a slightly positive zeta potential (+5 mV) showed cellular uptake in a concentration-dependent manner which was mainly by the clathrin-mediated endocytosis pathway, and exhibited a strong inhibitory effect on the growth of A549 lung cancer cells [78].
Recent strategies driving oral biologic administration
Published in Expert Review of Vaccines, 2021
Badriyah Shadid Alotaibi, Manal Buabeid, Nihal Abdalla Ibrahim, Zelal Jaber Kharaba, Munazza Ijaz, Ghulam Murtaza
There are several strategies for vaccine protection in GIT conditions, such as cargo adsorption on MPMNs surface and entrapment of vaccine into MPMNs (Figure 2). The immune system can readily recognize the surface-embedded antigens; however, their protection against the GIT environment is relatively complex, which requires additional surface modification for the enteric delivery of particles [81]. It is remarkable that several MPMNs have the intrinsic features of barrierless transfer across the epithelium and show its immunogenic action [82]. Moreover, M cells and intestinal cells recognize various particle sizes (their diameter ranges from a few hundred nm to few microns) [83–85] and transcytose them. Macrophages engulf smaller particles (less than 5 microns) and send them to the mesenteric lymph node for clearance through the mucosa after passing through the spleen [46,86,87]. The relatively larger particles have a more extended stay in the mucosa, resulting in an improved level of secretory IgA [86], indicating their slow release from the mucosal repository could be helpful for effective vaccination. Also, APCs and dendritic cells uptake MPMNs, and this functionality depend on their particle size, charge, and shape [47,88]. These parameters could be altered to potentiate immune response under the effect of the MPMNs vaccine. MPMNs can be decorated with different adjuvants and ligands to endow them with a variety of functions. Many peptides (such as arginylglycylaspartic acid) promote the binding of MPMNs with M cells, leading to their improved mucosal uptake [89–91]. Another study described encapsulation of toll-like receptor (TLR) targeting ligands in MPMNs, and the prepared microparticles promisingly targeted GALT in the colon [92].