Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis and angiogenesis.
The enhanced permeability and retention (EPR) effect is a controversial concept by which molecules of certain sizes tend to accumulate in tumor tissue much more than they do in normal tissues. The general explanation that is given for this phenomenon is that, in order for tumor cells to grow quickly, they must stimulate the production of blood vessels. VEGF and other growth factors are involved in cancer angiogenesis. Tumor cell aggregates as small as 150–200 μm, start to become dependent on blood supply carried out by neovasculature for their nutritional and oxygen supply. These newly formed tumor vessels are usually abnormal in form and architecture. They are poorly aligned defective endothelial cells with wide fenestrations, lacking a smooth muscle layer, or innervation with a wider lumen, and impaired functional receptors for angiotensin II. Furthermore, tumor tissues usually lack effective lymphatic drainage. All of these factors lead to abnormal molecular and fluid transport dynamics, especially for macromolecular drugs. This phenomenon is referred to as the "enhanced permeability and retention (EPR) effect" of macromolecules and lipids in solid tumors. The EPR effect is further enhanced by many pathophysiological factors involved in enhancement of the extravasation of macromolecules in solid tumor tissues. For instance, bradykinin, nitric oxide / peroxynitrite, prostaglandins, vascular permeability factor, tumor necrosis factor and others. One factor that leads to the increased retention is the lack of lymphatics around the tumor region which would filter out such particles under normal conditions.
Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticle-mediated drug delivery in order to combat the downfalls of conventional drug delivery. These nanoparticles would be loaded with drugs and targeted to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The conventional drug delivery system is the absorption of the drug across a biological membrane, whereas the targeted release system releases the drug in a dosage form. The advantages to the targeted release system is the reduction in the frequency of the dosages taken by the patient, having a more uniform effect of the drug, reduction of drug side-effects, and reduced fluctuation in circulating drug levels. The disadvantage of the system is high cost, which makes productivity more difficult, and the reduced ability to adjust the dosages.
Cell-penetrating peptides (CPPs) are short peptides that facilitate cellular intake and uptake of molecules ranging from nanosize particles to small chemical compounds to large fragments of DNA. The "cargo" is associated with the peptides either through chemical linkage via covalent bonds or through non-covalent interactions.
Sanford Burnham Prebys is a 501(c)(3) non-profit medical research institute focusing on basic and translational research, with major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The institute also specializes in stem cell research and drug discovery technologies.
CD49d is an integrin alpha subunit. It makes up half of the α4β1 lymphocyte homing receptor.
A biointerface is the region of contact between a biomolecule, cell, biological tissue or living organism or organic material considered living with another biomaterial or inorganic/organic material. The motivation for biointerface science stems from the urgent need to increase the understanding of interactions between biomolecules and surfaces. The behavior of complex macromolecular systems at materials interfaces are important in the fields of biology, biotechnology, diagnostics, and medicine. Biointerface science is a multidisciplinary field in which biochemists who synthesize novel classes of biomolecules cooperate with scientists who have developed the tools to position biomolecules with molecular precision, scientists who have developed new spectroscopic techniques to interrogate these molecules at the solid-liquid interface, and people who integrate these into functional devices. Well-designed biointerfaces would facilitate desirable interactions by providing optimized surfaces where biological matter can interact with other inorganic or organic materials, such as by promoting cell and tissue adhesion onto a surface.
Tenascin C (TN-C) is a glycoprotein that in humans is encoded by the TNC gene. It is expressed in the extracellular matrix of various tissues during development, disease or injury, and in restricted neurogenic areas of the central nervous system. Tenascin-C is the founding member of the tenascin protein family. In the embryo it is made by migrating cells like the neural crest; it is also abundant in developing tendons, bone and cartilage.
Neuropilin-1 is a protein that in humans is encoded by the NRP1 gene. In humans, the neuropilin 1 gene is located at 10p11.22. This is one of two human neuropilins.
Complement component 1 Q subcomponent-binding protein, mitochondrial is a protein that in humans is encoded by the C1QBP gene.
Arginylglycylaspartic acid (RGD) is the most common peptide motif responsible for cell adhesion to the extracellular matrix (ECM), found in species ranging from Drosophila to humans. Cell adhesion proteins called integrins recognize and bind to this sequence, which is found within many matrix proteins, including fibronectin, fibrinogen, vitronectin, osteopontin, and several other adhesive extracellular matrix proteins. The discovery of RGD and elucidation of how RGD binds to integrins has led to the development of a number of drugs and diagnostics, while the peptide itself is used ubiquitously in bioengineering. Depending on the application and the integrin targeted, RGD can be chemically modified or replaced by a similar peptide which promotes cell adhesion.
Sangeeta N. Bhatia, M.D., Ph.D. is an American biological engineer and the John J. and Dorothy Wilson Professor at MIT’s Institute for Medical Engineering and Science and Electrical Engineering and Computer Science (EECS) at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts, United States. Bhatia's research investigates applications of micro- and nano-technology for tissue repair and regeneration. She applies ideas from computer technology and engineering to the design of miniaturized biomedical tools for the study and treatment of diseases, in particular liver disease, hepatitis, malaria and cancer.
Tumstatin is a protein fragment cleaved from collagen that serves as both an antiangiogenic and proapoptotic agent. It has similar function to canstatin, endostatin, restin, and arresten, which also affect angiogenesis. Angiogenesis is the growth of new blood vessels from pre-existing blood vessels, and is important in tumor growth and metastasis. Angiogenesis is stimulated by many growth factors, the most prevalent of which is vascular endothelial growth factor (VEGF).
The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.
Lee Byung-heon (Korean: 이병헌) is a Professor of Biochemistry and Cell Biology in the School of Medicine at Kyungpook National University (KNU), South Korea. He received his M.D. license from Korean Medical Association in 1989. He received his B.S. from the School of Medicine, KNU in 1989, and his M.S. and Ph.D. in Biochemistry from KNU in 1991 and 1995. He was an Assistant Professor in School of Medicine at Dongguk University in 1996-2001 and a Visiting Investigator in the Sanford-Burnham Medical Research Institute, La Jolla, United States in 2001-2003. He joined KNU in 2003. He is currently a member of Korean Society for Biochemistry and Molecular Biology, the American Association for Cancer Research, and the American Society of Molecular Imaging. His main research interest is “discovery of tissue-specific homing peptides using phage display and their applications to molecular imaging and targeted therapy”. He is currently carrying out projects for the identification of homing peptides to tumor and atherosclerotic plaque and of phosphatidylserine- and blood clotting factor XIIIa-specific peptide ligands. He has published over 30 peer-reviewed papers, book chapters, and review articles. He has also filed several patents.
Gold nanoparticles in chemotherapy and radiotherapy is the use of colloidal gold in therapeutic treatments, often for cancer or arthritis. Gold nanoparticle technology shows promise in the advancement of cancer treatments. Some of the properties that gold nanoparticles possess, such as small size, non-toxicity and non-immunogenicity make these molecules useful candidates for targeted drug delivery systems. With tumor-targeting delivery vectors becoming smaller, the ability to by-pass the natural barriers and obstacles of the body becomes more probable. To increase specificity and likelihood of drug delivery, tumor specific ligands may be grafted onto the particles along with the chemotherapeutic drug molecules, to allow these molecules to circulate throughout the tumor without being redistributed into the body.
Quantum dots (QDs) are semiconductor nanoparticles with a size less than 10 nm. They exhibited size-dependent properties especially in the optical absorption and the photoluminescence (PL). Typically, the fluorescence emission peak of the QDs can be tuned by changing their diameters. So far, QDs were consisted of different group elements such as CdTe, CdSe, CdS in the II-VI category, InP or InAs in the III-V category, CuInS2 or AgInS2 in the I–III–VI2 category, and PbSe/PbS in the IV-VI category. These QDs are promising candidates as fluorescent labels in various biological applications such as bioimaging, biosensing and drug delivery.
iRGD is a 9-amino acid cyclic peptide and a molecular mimicry agent that was originally identified in an in vivo screening of phage display libraries in tumor-bearing mice. The peptide was able to home to tumor tissues, but in contrast to standard RGD peptides, also spread much more extensively into extravascular tumor tissue. It was later identified that this extravasation and transport through extravascular tumor tissue was due to the bifunctional action of the molecule: after the initial RGD-mediated tumor homing, another pharmacological motif is able to manipulate tumor microenvironment, making it temporarily accessible to circulating drugs. This second step is mediated through specific secondary binding to neuropilin-1 receptor, and subsequent activation of a trans-tissue pathway, dubbed the C-end Rule, or CendR pathway.
CendR is a protein motif that regulates vascular permeability. The mechanism is activated through neuropilin-1 receptor, which mediates a trans-tissue pathway, dubbed the C-end Rule, or CendR pathway.
Protein nanotechnology is a burgeoning field of research that integrates the diverse physicochemical properties of proteins with nanoscale technology. This field assimilated into pharmaceutical research to give rise to a new classification of nanoparticles termed protein nanoparticles (PNPs). PNPs garnered significant interest due to their favorable pharmacokinetic properties such as high biocompatibility, biodegradability, and low toxicity Together, these characteristics have the potential to overcome the challenges encountered with synthetic NPs drug delivery strategies. These existing challenges including low bioavailability, a slow excretion rate, high toxicity, and a costly manufacturing process, will open the door to considerable therapeutic advancements within oncology, theranostics, and clinical translational research.
