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Overview of Angiogenesis: Molecular and Structural Features
Published in Robert J. Gropler, David K. Glover, Albert J. Sinusas, Heinrich Taegtmeyer, Cardiovascular Molecular Imaging, 2007
Arye Elfenbein, Michael Simons
Upregulation of VEGF and its high affinity receptors is associated with hypoxia-induced angiogenesis and with tumor endothelium, rendering both potential candidates as markers of new vessel growth (11,12). However, high-affinity VEGF receptors represent only some of the membrane-bound proteins that transduce VEGF-initiated signals. The neuropilin class of membrane receptors bind both VEGF and semaphorins, with resultant effects found in neurons as well as endothelial cells (13). Neuropilins have been shown to selectively bind to particular molecular weight isoforms of VEGF; these receptors create profound downstream effects of growth and survival, in some cases amplifying VEGFR signaling (14). Further similarities between neural networks and the vasculature include observations that these molecules (along with the laminin-related family of netrins) are responsible for both axonal and vascular guidance during growth (15,16).
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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Thomas J. Anchordoquy, Yechezkel Barenholz, Diana Boraschi, Michael Chorny, Paolo Decuzzi, Marina A. Dobrovolskaia, Z. Shadi Farhangrazi, Dorothy Farrell, Alberto Gabizon, Hamidreza Ghandehari, Biana Godin, Ninh M. La-Beck, Julia Ljubimova, S. Moein Moghimi, Len Pagliaro, Ji-Ho Park, Dan Peer, Erkki Ruoslahti, Natalie J. Serkova, Dmitri Simberg
Several strategies to improve tumor penetration of compounds have been discussed. An approach to boost tumor permeability by tumor-penetrating peptides was presented. These peptides bind to a primary receptor specific for tumor blood vessels, tumor cells, and stroma, then undergo proteolytic cleavage and shift their affinity from the primary receptor to neuropilin-1. Binding to neuropilin-1 subsequently activates an endocytic/exocytic trans-tissue transport pathway, leading to a transient increase in tumor penetration of nanoparticles and small-molecule drugs [15]. This mechanism works especially well in starved tumors due to dependence of the transport process on metabolism.
Niosomes for Brain Targeting
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Nanocarriers for Brain Targeting, 2019
Didem Ag Seleci, Muharrem Seleci, Rebecca Jonczyk, Frank Stahl, Thomas Scheper
Neuropilin-1 (NRP-1) is a transmembrane protein overexpressed on the surface of both glioma and endothelial cells of angiogenic blood vessels (Li and Rossman, 2001; Nasarre et al., 2010; Hu et al., 2013). tLyp-1 (tumor homing and penetrating peptide) peptide with 7 amino acid (CGNKRTR), is as a ligand-targeted to the NRP-1 receptor with high affinity and specificity. Hence, tLyp-1 has been used as a targeting ligand for the delivery of drugs to the brain tumor (Hu et al., 2013).
Gold nanoparticles: a novel paradigm for targeted drug delivery
Published in Inorganic and Nano-Metal Chemistry, 2023
Kamalavarshini S, Ranjani S, Hemalatha S
Currently, in drug delivery applications some core or shell nanocomposites were implemented. Development of functionalized gold nanoshells coated with PEG and loaded with DOX on silica lattices showed complete removal of malignant sites present in mice after NIR laser treatment. The new addition to the GNPs family is the gold nanocages which were conjugated with bioactive molecules on its surface that aimed at targeting tumor cell receptors[52] while the inner core functioned for translocating chemo-drugs.[53] GNPs combined with microgels, titanium oxides, quantum dots are classified as hybrid nanosystems to makeshift in cancer therapeutics. One of the examples mentioned is magneto-GNPs hybrid systems devised for effective optical sensing, magnetic uncoupling and thermal excision of multifarious pathogens from a particular batch load. Moreover, to ease drug release internalization the understanding of decreased pH concentrations in the cytosol region of tumor cells were characterized. pH-sensitive GNP vectors have been fabricated and introduced into the cytoplasm of cancer cells, thereby leading to accelerated release of acid-sensitive antitumor drugs and greater concentrations of drugs in the acidic cytosol with increased cytotoxicity to the tumor cells. The disease and delivery entity should share the exact and precise communication link between each other thus guiding a more desired path in compound in vivo conditions for the vector to bring in the desired drug at the targeted location. Surface receptors which are expressed by tumor cells are harnessed for designing efficient, safe, and nontoxic curative entities. To target estrogen receptor-positive MCF-7 breast cancer cells, tamoxifen, anti-estrogen bound GNPS were selectively designed. Synergistic targeting of tumor cell lines was made possible by combinational formulations of two elective agents. The dual ligand-labeling GNP, that is, folate acid and epidermal growth factor receptors over-expressed in ovarian cancer cells are effectively and precisely targeted. Neuropilin-1 receptor, is a type of transmembrane glycoprotein and it also accounts for mediating angiogenesis was found to be expressed in high proportions in lung cancer, Osteosarcoma, pancreatic tumors, brain tumors, and other tumor types. These tumor types were treated experimentally with 5.2 nm platinum amalgamated with glutathione-coated GNPS for targeting the high concentration receptors.[54] Studies revealed that the glutathione concentrations were responsible in targeting hepatocyte by employing lactose surface-modified GNPs embedded with fluorescence –reporting drugs. The outcomes from this research showed that selective release of drug load from the modified GNPs administered into cytosol were observed only in high glutathione concentrations of hepatic cells. Therefore, conjugating anticancer therapeutics with GNPs provides a distinct and novel platform for personalized cancer treatments that can be of complete cure.