China
Africa
Explore chapters and articles related to this topic
Experimental Considerations for Scalable Magnetic Nanoparticle Synthesis and Surface Functionalization for Clinical Applications
Published in Nguyễn T. K. Thanh, Clinical Applications of Magnetic Nanoparticles, 2018
Alec P. LaGrow, Maximilian O. Besenhard, Roxanne Hachani, Nguyễn T. K. Thanh
The tripeptide RGD (arginin–glycin–aspartate) is present in numerous proteins of the ECM and is a ligand of integrins (αvβ3).118,119 The affinity between these two molecules is related to the protein’s conformation and has been the main strategy explored for the active targeting of MNPs to cancer cells. The integrin αvβ3 has an extracellular V-type structure in which each subunit has a ‘closed headpiece bent’ conformation. This structure corresponds to a weak affinity state. The fixation of a ligand, such as the RGD peptide, will lead to a conformational change in which the affinity is increased. Cyclic peptides are more often used than the linear equivalent since the latter was shown, in clinical trials, to accumulate strongly in the liver and not in the desired tumour cells.120 Also, the linear form of the peptide can have conformations with different affinities for the integrin αvβ3 and are more sensitive to proteolysis.
Polymeric Conjugates for Angiogenesis-Targeted Tumor Imaging and Therapy
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Amitava Mitra, Anjan Nan, Bruce R. Line, Hamidreza Ghandehari
To address the unfavorable pharmacokinetics of these cyclic peptides, investigators have studied their conjugation to hydrophilic polymers such as PEG. A comparative biodistribution study showed that free peptide had a more rapid tumor washout than a pegylated cyclic RGD conjugate. In contrast, the PEG–RGD conjugate showed a gradual increase in both tumor accumulation and tumor-to-blood ratios.139 Similarly, studies of 18F140 and 64Cu141 radiolabeled pegylated RGD have yielded high quality microPET images of glioblastoma xenografts with higher T/B ratios than the non-pegylated peptide.
Self-assembled Peptide Nanostructures and Their Applications
Published in Klaus D. Sattler, st Century Nanoscience – A Handbook, 2020
Cyclic peptides are those in which the polypeptide chain is connected through a circular sequence of bonds. The self-assembled tubular structures formed by cyclic-like peptides were first reported by Ghadiri et al. (1993). They reported the cyclic peptide with an even number of alternating d- and l- amino acids that formed β-sheet-like tubular nanostructures. The first cyclic peptide synthesized by this group was cyclo-(l-Gln-d-Ala-l-Glu-d-Ala)2 (Figure 2.10) This self-assembly is mediated in an acidic medium upon H-bonding interaction between the backbone amide groups, which are oriented perpendicular to the side chains, and the plane of the ring. The individual cyclic peptide monomers are stacked in a ring-shaped conformation to form a hollow structure while the side chains of the amino acid lie on the outside surface of the nanotubes. At alkaline pH, the more intermolecular repulsion between the negatively charged carboxylate side chains of aspartic acid would discourage the ring stacking and at the same time promote the dissolution of the peptide subunits in aqueous medium. However at acidic pH, upon protonation, the repulsive parameter is no longer present and so the attractive side-chain/side-chain H-bonding should occur, which provides the principal driving force in the self-assembly process. So, the controlled acidification of peptide solution promotes the spontaneous self-assembly of peptide subunits into the form of a tubular nanostructure. This tubular structure has a length of 100 nm and internal diameter of 7–8 Å. Electron microscopy images also support the tubular structure (Figure 2.10) (Ghadiri et al. 1993, Hartgerink et al. 1996).
‘Borono-lectin’ based engineering as a versatile platform for biomedical applications
Published in Science and Technology of Advanced Materials, 2018
Akira Matsumoto, Yuji Miyahara
Bandyopadhyay and Gao have made use of this chemistry as a means to accomplish peptide cyclization [105]. There is a growing interest in the synthesis of cyclic peptides mimicking the structure and function of their natural counterparts. Among a number of the peptide cyclization strategies, the disulfide chemistry represents so far the only non-permanent or reversible type of linkages enabling the design of ‘smart’ peptides that can turn on or off their activity in response to biological stimuli. Gao et al. demonstrated that iminoboronate linkages could also play this role. In particular, a series of RGD (an integrin-recognition motif) containing sequences bearing artificial boronate-functionalized amino acid moieties in a way flanking the above were designed and optimized so as to spontaneously yield mono- or bicyclizations via intramolecular iminoboronate formation (Figure 9). The iminoboronate linkages incorporated into these peptides were reversibly cleavable in response to acidification, oxidation, and addition of some exogenous small molecule modulators. Furthermore, fluorescence-labeled version of the iminoboronate-cyclized RGD peptides were tested for the binding with SKOV3 cells, an ovarian cancer cell line known to overexpress the αvβ3 integrin. As expected, the fluorescence staining of the cells was effectively switched when altering the pH between 7.4 and 6.0, under which the peptide undergoes conformational change between cyclized and linearized states.