RGD targeted delivery systems as anticancer treatment strategy

NEW RGD targeted delivery systems as anticancer treatment strategy
RGD targeted delivery systems as anticancer treatment strategy
Subject: – Pharmacology

Below are the main points the writer should consider for creating the whole of the review based thesis including abstract, materials/methods, discussion, conclusion and references (many references at the end, 30-50 references at least) , and I need the sources of materials used at the end.

The main subject is : “RGD based targeted drug delivery systems in cancer Chemotherapy and cancer treatment”.
The following points must be referred and expanded while writing the thesis:
What is integrin and what are its subtypes? To what receptors it is related to and upond its activation what happens?
Where integrins are found?
functions of integrins?
To what ligands integrin binds?
Intracellular functions of Integrins?
Integrins and other RGD based receptors, what happens to them in case of cancer or metastasis, or related diseases?
How Integrin mediated signalling pathway works?
RGD applications in tumor therapy and chemotherapeutics?
Structure, activation and interactions related to integrins?
Overall, how RGD or its related mechanisms can be used in the treatment of cancer? What may be its potential uses in Pharmacy or medicine in the future?

____________________________

I will not need a data analysis or data collection. But when you finish with writing up, please be sure to provide followings:
Revisions within 30 days
Copy of the cited sources

Please find attached some articles and resources (do not use wikipedia, I attached it for the purpose of providing additional information). Feel free to use them all, but you obviously need to find even more articles or resources for the thesis.

I hope this helps. Should you have additional queries please do not hesitate to contact me straight away. I were not able to send these files on the system, which is the reason I am sending them via this email.
Pharmacology
Student’s Name:
Affiliation:
Date

Pharmacology
Rgb Targeted Delivery System
The use of nanoparticles for the distribution and targeting of pharmaceutical, therapeutic and diagnostic proxies in cancer rehabilitationtakesconventionalnoteworthycourtesy in latest years. Nanoparticles exist fromanextensivevariety of ingredientsin addition to encapsulate or solubilize chemotherapeutic agents aimed at improved supply in vivo or to provide, electrical and optical magnetic and unique properties for therapyas well as imaging. Numeroususeful nanoparticles at the present have been validated, together with some clinically permitted liposome prescriptionconstructions and metallic imaging go-betweens. Subsequentgroups of nanoparticle-based study is engagedon the consolidation of roles into strategically contrived multifunctional schemes, eventually realizing the therapy for the individual.by means of molecular detection , multiplexed nanoparticles are capable of identifying malignant cells, enhanced contrast is provided assign in visualizing the location of malignant cells by use of medical imaging procedures, with minimum side effects, disease cells are killed through selective targeting of drugs, monitoring in real time treatment. The recent progress have been highlighted for multifunctional systems engineering by this article, new development as well as economic and scalable methods for preparation module of multiple nanoparticles have been precisely and simply tailored.
What is integrin?
Integrin, this are proteins whose role involuntarily, by ascribing the cell cytoskeleton to the, biochemically and extracellular matrix (ECM), by detecting whether linkage has ensued.The family of integrin is consist of proteins having beta and alpha subtypes, they form transmembrane heterodimers. By ascribing receptors for transduce biochemical signals and extracellular ligands into the cell, over and done with downstream effector proteins. By performing bidirectional, they transmit information inside-out and outside-in. Integrin heterodimer consists of a beta (ß) as well as an alpha (a) subunit connected by non-covalentinteractions (Bhattacharya et al, 2009). Thebetaas well as alpha groups show no homology at all,never the less,conserved regions are seen among both subtypes groups. The alpha subunit leg contains of a thigh as well as 2 domainscalf that issue support the ligand essential head made by a ß-propeller sphereby 7 duplicationsforming the vanes (Ginsberg, Partridge & Shattil, 2005). The propeller vane domains encompassof EF-hand domains on the inferioradjacent; ligard binding are affected by allosteric ally. A supplementary aI sphere. Comprising of 200 residues is locatedright in some vertebrate a chains amid propeller recaps 2 and 3. It comprises of a metal-ion dependent on adhesion site (MIDAS)significant for ligand binding. Else ß subunit encompasses 4 cysteine-rich. Epidermal growth factor (EGF) reprises, hybrid domain, ßI as well as a plexin-semaphoring-integrin domain. Similar to aI, the contains ßI domain comprisesof a metal-ion dependent on adhesion site aimed at ligand binding as well as additional adjusting site ,ADMIDAS, contiguous to metal-ion reliant on adhesion site ,subdued by Ca2+ and triggered by Mn2+for binding ligand (Humphries, Byron & Humphries, 2006).
i) Ligand binding
A ßI domain fixes ligand together by the ß- propeller or with aI through metal-ion reliant on adhesion sitein a Mg2+reliant onmannerat the crossing point in the headpiece. Although Asp carboxyl group coordinates the ßI metal-ion reliant on adhesion site Mg2+,on the side chain hydrogen of the Arg of the RGD ligand binds straight to the Asp in domains 2 and 3 of ß-propeller (Friedland & Boettiger, 2009).
ii) Dimerization
This dimerization take placeon the a chainthrough the ß-propeller superficial as well as the Beta hybrid domain chain in the cytoplasm (Geiger, Spatz & Bershadsky, 2009). Sequences at these intermingling surfaces seem like to regulate the specificity of manaclemixture. The dimers partakeremainedrevealed to be steadied and endurelethargic by hydrophobic connectionsin addition to electrostatic salt bridges at the inner and outer -membrane proximal statescorrespondingly.
iii) Interactions
ß-chain cytoplasmic tail is well-known to fix to protein connectersover NPxY/motifs this stimulates the integrin by breaching the salt bridge amongst the dimer, the connecter proteins encouragelink to actin yetmiddlethreads have been implicated through vimentin.
Structural adaptors link integrinindirectly to the cytoskeleton Scaffolding adaptors (e.g. kindlin, paxillin) proceduresbonds between pivotallinkage proteins Catalytic connecters propagate signal transduction from adhesion sites. Phosphorylation state of cytoplasmic tail residues curb the antagonism between connecters for binding hereafter the succeeding cytoskeletal interfaces of integrinin addition toreply.
Human beings have aminimum8 ß subtypes and 18 a subtypes which composedmake 24 recognizedrequisitecouples for the integrin’sheterodimer.Thedistinctive of subunits integrin is theircapability to bind diverse matrix moleculesconveyed by the heterogeneity of themonomers (Humphries et al, 2000, 2003, 2007). Common ECM components that are integrinbound include (Katagiri et al, 2003);
1. Glycoproteins (e.g. tenascin C,
2. Laminin
3. Thrombospondin
4. Collagen (triple helical GFOGER)
5. Fibronectin (RGD, LDV)
6. Fibrinogen (RGD)
Integrin’sexist broadly divided into fourclassesdepending on their ligand-specificity
1. Laminin receptors (a1ß1, a2ß1, a3ß1, a6ß1, a7ß1, and a6ß4)
2. RGD receptors (a5ß1, aVß3,aVß1, aVß5, aVß6, aVß8, and aIIbß3)
3. Collagen receptors (a1ß1, a2ß1, a3ß1, a10ß1, and a11ß1)
4. Leukocyte-specific receptors (aLß2,aMß2, aXß2, and aDß2)
Integrin are found in metazoa. They work alongside receptors like selectins, cadherin, immunoglobulin superfamily cell adhesion molecules, they mediate cell to cell interaction. Ligards for integrin also include fibronectin, collagen , laminin and vitronection (Askari et al, 2010).
Integrin functions
Solid confirmations affirmed most CAMs as basic segments of cell film, as well as pivotal parts in the synaptic development, dendritic spine morphology and synaptic versatility . Among which Cadherin, Ephrin and Eph, Neurexin and Neuroligin indicated incredible essentialness in interceding synaptic capacities (Lau et al, 2009). For example, in synaptogenesis the collaboration of presynaptic Neurexin and postsynaptic Neuroligin, both could experience elective joining to deliver a huge number of particular associations with decide neurotransmitter contact. In vivo and in vitro trial comes about indicated Neuroexin-Neuroligin communications in controlling neurotransmitter arrangement and particular . Generally, Neuroexin likewise manages presynaptic calcium channel work . Ephrins have been of predominance for grown-up neurogenesis and Eph-Ephrin collaborations for axon direction or dendritic spine morphogenesis (Calderwood et al, 2003). In unique, postsynaptic EphB has a few areas empowering its bidirectional flagging capacities in many parts controlling synaptogenesis both in vivo and in vitro (Gahmberg, 2009). Ephs and Ephrins adjust synaptic versatility by interceding glutamate receptor NMDAR subordinate synaptic pliancy in Mossy fiber-CA3 and Schaeffer insurance CA1 hippocampal neural connections, yet the basic component stays poor known . Cadherin as another group of CAMs, are generally communicated at pre-and postsynaptic terminals. N-Cadherin can tie to ß-catenin and after that interface with actin cytoskeleton, together balance out the synaptic morphology in basal conditions or system exercises. Cadherins are additionally appeared to be required in numerous synaptic flow like presynaptic capacity, transient versatility and long haul potentiation (LTP) . N-Cadherin-ß-catenin complex can likewise manage AMPAR trafficking, which is a noteworthy type of synaptic quality changes .
Together these CAMs are highlighted for essential players in synaptic advancement and capacity. Be that as it may, integrins have gotten little thought paying little mind to numerous subtypes of integrins exist in the CNS, for the most part aVß3 and ß1 integrins, which are generally communicated in the neurons and particularly in the neurotransmitters. Past reviews have somewhat clarified integrin could impact synaptic capacity. Overexpression or loss of integrin prompts to synaptic adequacy changes, in this way regulate NMDAR interceded synaptic streams identified with LTP, however the auxiliary system is obscure ; In the Drosophila Volado mutant stopped integrin expression would dispense with fleeting olfactory . All the more as of late, spine rebuilding is observed to be associated with ECM-integrin exercises, and ß1 integrin mutants would bring about working memory, spatial memory and LTP shortages, additionally connected integrin motioning with AMPA receptor respectable qualities.
ForLiganded integrin to function as abidirectional signal transmitter,
1. Adaptor proteins bind to the integrin cytoplasmic domains, thereby connecting integrin to the cytoskeleton.
2. Integrin undergo a process calledactivation, during which conformationalchanges expose the headpiece (ßI andhybrid domain) for ligand binding. This can be initiated bythe binding of adaptor proteins and/orligands.
3. Integrin’smicro cluster laterally foreffective ligand binding.
Integrin are able to trigger various indication cataracts transduction. Vivo functions are affected by a mixture a and ß subtypes,. These include performance of cells and association of tissues. Indicatingpassageway is initiated byintegrin activation is created on the biologicalcontext, as well as the ligands bound. Subject to the combination of such factorsshort-term and long-term responses a variety mayresult. Following integrin activation, Substrate stiffness has as well beenshown to mark the type of adhesionstructure formed.
Some study have revealed the progress ofpod some-like adhesion organizations in non-transformed fibroblasts developed on fluid,membrane based substrates. In this situation, RGD (Arg-Gly-Asp) peptides,was shown to activate integrin by bounded membrane. Focal adhesion formation are initiated by RGD –activated integrin growing on a rigid surface (Hughes, 1996).The linkageconstructionsformed on the softer substrates had alikemorphology and temperament to classicpodosomes originate in macrophages.in spite ofbeing protrusive, thephysiological role of podosome-likestructures is still mysterious. The developmentof these podosome-like constructions in theabsence of forces was facilitated by p85betaenrollment and confined PIP3augmentation at thelinkage sites; equally are notpragmatic in principal adhesion formation.Improved production of PIP3 at presenttriggered N-WASP instigationas well as RhoA -GAP ARAP3conscription, which down adjusts RhoA-GTPlevel in pod some-forming cells.
RGD applications in tumor therapy and chemotherapeutics
Nanotechnology has been used to revolutionize therapy and cancer diagnosis. Bringing hope to cancer patient, materials science and protein engineering have contributed to novel nanoscale targeting. For clinical use, several nanocarriers have been allowed (Larson et al, 2009). But a few only have been approved nanocarriers incorporating molecule to targeted cancer cells and selectively binding. We therefore emphasize of challenges in treatment of cancer.
To what ligands integrin binds?
Proteins that contain the Arg-Gly-Asp (RGD) connection site, together with the integrins that serve as receptors for them, constitute a noteworthy acknowledgment framework for cell bond. The RGD grouping is the cell connection site of countless extracellular network, blood, and cell surface proteins, and almost 50% of the more than 20 known integrins perceive this arrangement in their bond protein ligands. Some different integrins bind to related successions in their ligands (Johnson, 2009). The integrin-restricting movement of bond proteins can be replicated by short manufactured peptides containing the RGD arrangement. Such peptides advance cell bond when insolubilized onto a surface, and restrain it when exhibited to cells in arrangement. Reagents that quandary specifically to just a single or a couple of the RGD-coordinated integrins can be composed by cyclizing peptides with chose groupings around the RGD and by integrating RGD copies (Coyer et al, 2013). As the integrin-intervened cell connection impacts and directs cell movement, development, separation, and apoptosis, the RGD peptides and mirrors can be utilized to test integrin works in different organic frameworks. Tranquilize configuration in light of the RGD structure may give new medicines to infections, for example, thrombosis, osteoporosis, and malignancy.
Intracellular elements of Integrins?
Integrins are a and ß heterodimers with every subunits cross layer once. Most polypeptides are extracellular and just two short cytoplasmic spaces are intracellular. Created by two subunits with mixes, the mammalian integrins appear to have advanced for various parts. As a transmembrane protein, integrin conveys extracellular network (ECM) with intracellular cytoskeleton to send or get signals. With the capacity of reacting to tie many flag transduction pathway proteins, integrin can enact, deactivate or manage downstream atoms in different physiological procedures . To comprehend integrin as synaptic mechanical stabilizer we ought to know the auxiliary coordination of integrin connecting ECM and cytoskeleton. Amid cell relocation, integrin is enacted to group and shape central bond, amid which the integrin joins actin cytoskeleton and ECM. Integrin thickness is higher in sliding parts of the cell while in the cell front is stationary, and this higher thickness includes a quick integrin ß3 turnover. Grouped integrins requires complex arrangement comprising of integrin, ligands, talin and PI(4,5)P2 lipid to progressively redesign, which may likewise recommended a conceivable instrument in the sensory system .
Integrins and other RGD based receptors, what happens to them in case of cancer or metastasis, or related diseases?
Auto is a transmembrane protein that is communicated in different epithelial and endothelial cells. Auto intervenes adenoviral contamination, and also adenovirus-interceded oncolysis of AxdAdB-3, an E1A/E1B twofold confined oncolytic adenovirus, in prostate tumor cells. This review additionally surveyed the remedial adequacy of AxdAdB-3 with Arg-Gly-Asp (RGD)- fiber adjustment (AxdAdB3-F/RGD), which empowers integrin-subordinate contamination, in prostate growth. Defenselessness of prostate tumor cells LNCaP, PC3, and DU145 to adenovirus disease was connected with CAR expression (Harburger & Calderwood, 2009). The majority of the prostate tumor cell lines communicated integrin avß3 and avß5. AxdAdB-3 was more cytopathic in CAR-positive prostate growth cells than in CAR-negative cells, though AxdAdB3-F/RGD brought about intense oncolysis in both CAR-positive and CAR-negative prostate malignancy cells. Interestingly, AxdAdB3-F/RGD was not cytopathic against ordinary prostate epithelial cells, RWPE-1. Intratumoral infusion of AxdAdB3-F/RGD into CAR-negative prostate disease cell xenografts in naked mice repressed tumor development. The present review shows that E1A/E1B twofold confined oncolytic adenovirus with a RGD-fiber adjustment upgrades disease effectiveness and hostile to tumor movement in CAR-lacking prostate growth cells, while saving ordinary cells. Future reviews will assess the helpful capability of AxdAdB3-F/RGD in prostate disease (Ivaska et al, 2002).
How Integrin mediated signalling pathway works?
Reliable with the past exploratory outcomes, integrin ß3 is in charge of synaptic scaling amid system changes just at the postsynaptic level; however information from separated societies and integrin expression designs in the neurotransmitters propose there might be other integrin subtypes make up for the scaling procedure. In that many hopefuls could be chosen for future exploratory outline.
To regulate the synaptic quality onto homeostasis integrin can improve both presynaptic quantal substance by upgrading neurotransmitter discharge viability, and increment postsynaptic quantal size by balancing out the AMPA receptor. So how integrin as cell attachment atom send data to the presynaptic terminal to direct? Integrin as transmembrane protein could connect ECM and actin; actin is available at presynaptic terminals and through actin-synapsin-vesicles to progressively assemble the vesicle pool ; actin rebuilding requiring Rho group of little GTPases is ensnared in neurotransmitter development, and actin has been accounted for critical for the bunching of the hold synaptic vesicle pool, the conveying of synaptic vesicles to the dynamic zone and synaptic vesicle exocytosis . Present of these discoveries the integrin and actin cytoskeleton coordination in a trans-synaptic way would answer how synaptic scaling is calibrated. One potential key variable is talin, framing the central bonds of cells and ECM, and tie to the integrin, is a connector amongst integrin and actin cytoskeleton. Talin ties with F-actin, and can tie to ß3 integrin restricting site at its F3, and talin initiation needs the support of Rap1 . In addition, talin is as of late observed to be available at neuron, however its capacity stays obscure. Past reviews uncovered a key part of talin, that after talin brokenness through PIP kinase interference, the actin elements and synaptic vesicle endocytosis are extremely annoyed . Without a doubt, talin is likely to be a key modulator in trans-synaptic flagging pathway.

RGD applications in tumor therapy and chemotherapeutics?
Chemotherapy has been the primary approach for the systemic treatment of cutting edge or metastatic illnesses for the greater part century. Amid the cells division prepare, chemotherapeutics is fit for murdering multiplying cells, subsequently influencing atypical cells. While very proficient in avoiding infection movement, be that as it may, chemo-helpful operators are regularly absence of selectivity for distorted cells. Their lethality to ordinary cells and non-unhealthy tissues, particularly to quickly developing cells, for example, blood, bone marrow and mucous layer cells, cause genuine symptoms that force to administrate the chemotherapeutic operators at problematic measurements 1. Due to characteristic or procured resistance of unusual cells, advantages of the chemotherapeutic operators are likewise regularly restricted 2. The effectiveness of the treatment can be expanded by heightening the dosages, yet this alternative usually brings about impressive danger issue and in this way is once in a while considered. Specific conveyance of chemotherapeutic operators to the illness site subsequently speaks to a noteworthy test for enhancing current chemotherapy result 3. Focused on conveyance of chemotherapeutics is a rising treatment methodology supplied with malady focusing on capacities and conveying cytotoxic parts by empowering the particular conveyance of chemotherapeutic specialists to deviant tissues, in this way expanding their neighborhood adequacy while restricting their fringe danger. Obviously, the achievement of this approach is intensely on the sane choice of fitting organic targets.
Structure, activation and interactions related to integrins?
Integrins are extensive, film traversing, heterodimeric proteins that are fundamental for a metazoan presence. All individuals from the integrin family embrace a shape that looks like an expansive “head” on two “legs,” with the head containing the destinations for ligand official and subunit affiliation. The vast majority of the receptor dimer is extracellular, however both subunits cross the plasma film and end in short cytoplasmic areas. These spaces start the get together of vast flagging buildings and in this way connect the extracellular grid to the intracellular cytoskeleton. To permit cells to test and react to an element pericellular environment, integrins have developed a profoundly responsive receptor enactment component that is controlled basically by changes in tertiary and quaternary structure.
Generally, how RGD or its related instruments can be utilized as a part of the treatment of tumor? What might be its potential uses in Pharmacy or prescription later on?
The capability of peptides in malignancy treatment is apparent from an assortment of various methodologies that are accessible to address the movement of tumor development and engendering of the malady. Utilization of peptides that can specifically target disease cells without influencing ordinary cells (focused on treatment) is developing as a substitute procedure to routine chemotherapy (Hynes, 2002). Peptide can be used straightforwardly as a cytotoxic specialist through different instruments or can go about as a bearer of cytotoxic operators and radioisotopes by particularly focusing on malignancy cells. Peptide-based hormonal treatment has been broadly considered and used for the treatment of bosom and prostate tumors. Colossal measure of clinical information is right now accessible verifying the proficiency of peptide-based malignancy antibodies. Mix treatment is developing as an essential procedure to accomplish synergistic impacts in battling malignancy as a solitary technique alone may not be sufficiently effective to yield positive outcomes (Barczyk ea al, 2009). Joining immunotherapy with ordinary treatments, for example, radiation and chemotherapy or consolidating an anticancer peptide with a nonpeptidic cytotoxic medication is a case of this developing field.
In summary, Integrins are a and ß heterodimers with every subunits cross film once. Most polypeptides are extracellular and just two short cytoplasmic spaces are intracellular. Formed by two subunits with blends, the mammalian integrins appear to have developed for various parts. As a transmembrane protein, integrin conveys extracellular lattice (ECM) with intracellular cytoskeleton to send or get signals. With the capacity of reacting to tie many flag transduction pathway proteins, integrin can enact, deactivate or control downstream atoms in numerous physiological procedures. To comprehend integrin as synaptic mechanical stabilizer we ought to know the basic coordination of integrin connecting ECM and cytoskeleton. Amid cell relocation, integrin is actuated to bunch and shape central grip, amid which the integrin joins actin cytoskeleton and ECM. Integrin thickness is higher in sliding parts of the cell while in the cell front is stationary, and this higher thickness includes a quick integrin ß3 turnover. Grouped integrins requires complex development comprising of integrin, ligands, talin and PI(4,5)P2 lipid to progressively rebuild, which may likewise recommended a conceivable instrument in the sensory system (Barczyk et al, 2014).
References
Askari JA, Tynan CJ, Webb SED, Martin-Fernandez ML, Ballestrem C, and Humphries MJ. Focal adhesions are sites of integrin extension. J. Cell Biol. 2010; 188(6):891-903. [PMID: 20231384]
Barczyk M, Carracedo S, and Gullberg D. Integrins. Cell Tissue Res. 2009; 339(1):269-80. [PMID: 19693543]
Bhattacharya R, Gonzalez AM, Debiase PJ, Trejo HE, Goldman RD, Flitney FW, and Jones JCR. Recruitment of vimentin to the cell surface by beta3 integrin and plectin mediates adhesion strength. J. Cell. Sci. 2009; 122(Pt 9):1390-400. [PMID: 19366731]
Calderwood DA, Fujioka Y, de Pereda JM, García-Alvarez B, Nakamoto T, Margolis B, McGlade CJ, Liddington RC, and Ginsberg MH. Integrin beta cytoplasmic domain interactions withphosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling. Proc. Natl. Acad. Sci. U.S.A. 2003; 100(5):2272-7. [PMID: 12606711]
Coyer SR, Singh A, Dumbauld DW, Calderwood DA, Craig SW, Delamarche E, and García AJ. Nanopatterning reveals an ECM area threshold for focal adhesion assembly and force transmission that is regulated by ntegrin activation and cytoskeleton tension. J. Cell. Sci. 2012; 125(Pt 21):5110-23. [PMID: 22899715]
Friedland JC, Lee MH, and Boettiger D. Mechanically activated integrin switch controls alpha5beta1 function. Science 2009; 323(5914):642-4. [PMID: 19179533]
Gahmberg CG, Fagerholm SC, Nurmi SM, Chavakis T, Marchesan S, and Grönholm M. Regulation of integrin activity and signalling. Biochim. Biophys. Acta 2009; 1790(6):431-44. [PMID: 19289150]
Geiger B, Spatz JP, and Bershadsky AD. Environmental sensing through focal adhesions. Nat. Rev. Mol. Cell Biol. 2009; 10(1):21-33. [PMID: 19197329]
Ginsberg MH, Partridge A, and Shattil SJ. Integrin regulation. Curr. Opin. Cell Biol. 2005; 17(5):509-16. [PMID:16099636]
Harburger DS, and Calderwood DA. Integrin signalling at a glance. J. Cell. Sci. 2009; 122(Pt 2):159-63. [PMID:19118207]
Hughes PE, Diaz-Gonzalez F, Leong L, Wu C, McDonald JA, Shattil SJ, and Ginsberg MH. Breaking the integrin hinge. A defined structural constraint regulates integrin signaling. J. Biol. Chem. 1996; 271(12):6571-4. [PMID: 8636068 ]
Humphries JD, Byron A, and Humphries MJ. Integrin ligands at a glance. J. Cell. Sci. 2006; 119(Pt 19):3901-3. [PMID: 16988024]
Humphries JD, Wang P, Streuli C, Geiger B, Humphries MJ, and Ballestrem C. Vinculin controls focal adhesion formation by direct interactions with talin and actin. J. Cell Biol. 2007; 179(5):1043 57. [PMID: 18056416]
Humphries MJ, Symonds EJH, and Mould AP. Mapping functional residues onto integrin crystal structures. Curr. Opin. Struct. Biol. 2003; 13(2):236-43.[PMID: 12727518]
Humphries MJ. Integrin structure. Biochem. Soc. Trans. 2000; 28(4):311-39. [PMID: 10961914]
Hynes RO. Integrins: bidirectional,allosteric signaling machines. Cell 2002; 110(6):673-87. [PMID:
Ivaska J, Whelan RDH, Watson R, and Parker PJ. PKC epsilon controls the traffic of beta1 integrins in motile cells. EMBO J. 2002; 21(14):3608-19. [PMID: 12110574]
Johnson MS, Lu N, Denessiouk K, Heino J, and Gullberg D. Integrins during evolution: evolutionary trees and model organisms. Biochim. Biophys. Acta 2009; 1788(4):779-89. [PMID: 19161977]
Katagiri K, Maeda A, Shimonaka M, and Kinashi T. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat. Immunol. 2003; 4(8):741-8. [PMID: 12845325]
Larson RS, Corbi AL, Berman L, and Springer T. Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily. J. Cell Biol. 2009; 108(2):703-12. [PMID: 2537322 ]
Lau T, Kim C, Ginsberg MH, and Ulmer TS. The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling. EMBO J. 2009; 28(9):1351-61. [PMID: 19279667]
This is like the continuation of your previously written RGD paper.

-The write up must be in masters level and should consist of 8 pages.

– I need 15-20 references.

-Please stick to the following guidelines and focus your work on covering all the points in detail:

1. How RGD-drug link as anticancer therapy works, what are the mechanisms involved?

2. There are certain hypothesized advantages for RGD linked drugs such as:

• Increased uptake of drug
• Increased efficacy of drug
• Lower side effect

– Were these results as expected according to the studies (consider both review articles and research articles in field)
– What other potential advantages would exist? Why RGD linked drug delivery would be beneficial?

3. What type of linker(s) are required to connect RGD with drug? PEG is one of them, what about others? And how these linkers can be linked to RGD? (synthetically, adding functional groups etc.?) What type of conjugation technique can be used for such linkage?

4. Compare various types of RGD systems. Discuss advantages and disadvantages of each. Search for review papers for these.

5. RGD-linked drug uses:

– RGD-drug
– RGD-polypeptide/protein
– RGD-drug delivery system
– RGD-diagnosis imaging
How RGD can be used for the purposes listed above? Discuss in detail.
6. What type of drug molecules can be RGD linked drug molecules? (Small molecule drugs? Certain anticancer drugs having special structures? Why?) Discuss and comment.

7. How RGD-linked drugs, when administered to humans, will likely interact or affect cells, or tissues? With what mechanisms and why would these be beneficial or promising for cancer treatments? What would be the difference from already existing cancer medications or treatments available?

The following points must be referred and expanded while writing the thesis:

What is integrin and what are its subtypes? To what receptors it is related to and upond its activation what happens?

Where integrins are found?

functions of integrins?

To what ligands integrin binds?

Intracellular functions of Integrins?

Integrins and other RGD based receptors, what happens to them in case of cancer or metastasis, or related diseases?

How Integrin mediated signalling pathway works?

RGD applications in tumor therapy and chemotherapeutics?

Structure, activation and interactions related to integrins?

Overall, how RGD or its related mechanisms can be used in the treatment of cancer? What may be its potential uses in Pharmacy or medicine in the future?

find the cost of your paper