Tumour cell often differ in the structure of cell surface markers present on them. These are known as 'Tumour associated glycopeptide antigens' and even though the difference in structure (of these cell surface markers) is not significant and invisible to our immune system, the information can be utilized for designing cancer vaccines. Often the glycopeptides antigens are over expressed in cancer cells.

I am not doing study in this project.

I interest surface modification polymer and solid material with plasma and laser

Thanks

Thank you sir .

Thank you sir for your valuable information, sir actually I want to develop photodynamic therapy drug which will go to the nucleus and by photo activation will destroy the DNA strand of cancer cell.That 's why i want to target cancer cell only not healthy cell. So can you please suggest any thing more.

I don't know if you receive my previous response so I did it again. You must construct a covalent complex made of 3 parts :1-A biostable oligonucleotide recognizing the mutated or modified sequence of the cancer gnee(s) 2-your photodynamic effector 3-A vector platform able to penetrate specifically cancer cells and overcome biological barriers.Tis latter point s the most difficult to obtain and very few team in the world have got success.Good luck!

Thank you very much sir, will you please tell something about the vector platform.

I have always heard that cancer cells have folate receptors over-expressed. That means that if you put folic acid in your systems, that could enhance the endocytosis of your system by cancer cells. I remember have seen papers were they use that ligand to target mainly cancer cells, but haven't got the references right now (I'm sure that you can find something about this)

The problem is that this receptor is also present in some normal cells.... so probably your system will also be endocytosed by normal cells in some extension.

in this context i would say that MTX-(Methotextrate sodium) an antifolate metabolte is used to inhibit the growth and proliferation of cancer causing tumour cells

Thank you Alejandro Díaz-Moscoso, & Abhishek for your suggestions.

Cancer cell have accelerated division. Rho/Rac activated (with GTP) induces growth (and independient growth). GEFs put GTP on Rho, are about 20 and are oncogenes. Then GAPs return to GDP form inactivating. GEFs acts on the Rho-GDP membrane bound. Problems on GAP or GEF alter the cell division. I don't know if it can help.

I'm according with Alejandro, one of best strategy to target at cancer cells is the expression of folate derivatives at surface of vectors. Another way is empoiment of nanosystems (SLN, NLC, etc...). Their nanometric dimensions emprove uptake in cancer cells by EPR effect. I'm a Ph.D at this tematic, contact me if you want.

The vector must have a molecule recognizing the surface of the cancer cells ( folate receptor is a good candidate ,as said by your follower) and an agent increasing the cell penetration ( for example a cell penetrating peptide) . The problem the most difficult to resolve is how to go from blood to tumor tissue because of the high interstitial pressure inside the tumor even if the leaky nature of tumor vessels allow nanovectors to go out the vessels and penetrate few micrometers ( It has been calculated that the time to go until the center of the tumor could be 1 year!). There are also other barriers inside the tumor (enzymes, binding biomolecules, crowded cells,etc). There is no universal solution. I let you because I saw that specialists of the question are now helping you ( I am not at all a specialist of this field). Good bye.

thank you Gerard Sir bye bye...............................

Thank you Roberto & Ana María

Roberto, can you please tell me some thing more about SLN, NLC .

Cancer cell needs more glucose, it's possible more insulin activating.

Thank you Ana María ,actually now i am trying to use glucose moity on my pdt drug

Docosahexaenic acid (DHA) was applied to prepare a targeted Taxol conjugate against colon cancer. Cancer cells need polyunsaturated fatty acids to proliferate. You could use estrogens or SERMs to target breast and ovarial cancers, there's much literature about it. Indeed, photodynamically active porphyrins themselves were applied for tumor targeting of platinum complexes by Henri Brunner since tumor cells need porphyrin. Tyrosinase is located in the membrane of melanoma cells, so you could try to attach suitable tyrosinase inhibitors to your drug, there's evidence that pdt efficacy is enhanced upon tyrosinase inhibition. I'm sure the Sun God will help you ;-)

Thank you very much for your very useful information , but one thing I would like to ask you is that,if I use tyrosinase inhibitor will not they inhibit the normal cell function .Actually I am new in this field so I may ask a lot question to you, when you are free please do reply .

That's a good question, Aditya, and probably concerns all fields of drug targeting, also non-malignant cells need glucose, fatty acids, vitamins and so on, but cancer cells (depending on the type of cancer) have an enhanced expression of the corresponding transporters because they need more of these compounds than most non-malignant cells. In your special case you have another selectivity enhancing component, your laser source which activates your drug. Concerning melanoma, you can direct the laser light on the affected skin sites and thus only kill the cancer cells. In the case of melanoma metastases in the lung, liver and brain, only the melanoma metastases should present tyrosinase in contrast to surrounding lung, liver and brain cells. In these cases there's the question of availability of the metastasis towards endoscopy, since for the therapy you will have to introduce the light source endoscopically for some minutes into the body of the patient, especially metastasis in the brain are sometimes difficult to treat.

Thank you sir, again I have one more question if I use tyrosinase inhibitor in my ligand system i.e. phenol containing more than one hydroxy groups ,it will bind to the metal through the hydroxy group then how could it act as inhibitor ?

Of course you have to choose the right inhibitor, if the inhibitor reacts with your pdt drug it won't make sense to use such a compound. But there are also tyrosinase inhibitors without free phenolic hydroxy groups. If your pdt drug consists of soft metals like Pt or Au you might also use phenolic tyrosinase inhibitors, they shouldn't coordinate significantly to oxo-ligands in contrast to hard metals like Fe or Cu.

Thank you very much sir, I am trying to make iron based PDT drugs so tyrosine inhibitors with out free phenolate oxygen will be good for me , I think your suggestion will help me a lot ......

If you use a ferrocene-based PDT it should also work with phenolic tyrosinase inhibitors.

Thank you sir actually I am trying with Dipyrromethane derivative of ferrocene ,what is is your opinion about this?

Yes, you could attach a tyrosinase inhibitor to suitable ferrocene derivatives via a linker system. If you want to use ferrocenyl-dipyrromethane for the preparation of porphyrins you could react it with benzaldehydes which are modified with an inhibitor.

Thank you very much sir,actually I am unable to understand your last line " which are modified with an inhibitor."please explain me this one when you have free time ,don't mind I am asking you so many Questions .

I see, that last sentence is not clear. Well, the acid-catalysed reaction of dipyrromethanes with benzaldehydes gives substituted porphyrins, and I meant that a benzaldehyde derivative that is linked to a tyrosinase inhibitor via a suitable linker system should be able to react with ferrocenyldipyrromethane to give a ferrocenylporphyrin-tyrosinase-inhibitor conjugate pretty suitable to treat melanoma.

Thank you very much sir ,now I clearly understand it is a very good idea,I will try this one.

Don't forget to check if the tyrosine kinase inhibitor and its conjugate are internalized into the cancer cell

C'est vrai, cher Monsieur Perret, et il doit examiner que l'activité de l'inhibiteur (de tyrosinase, pas de tyrosine kinase, nous voulons attaquer le cancer de la peau par cette enzyme) n'est pas disparu dans la substance nouvelle. Well, I need practice ;-) What I want to say is that Dr Perret is right, if you have prepared your compound you should check if it is accumulated in melanoma cells (compared with other cancer types or non-malignant cells), and if the tyrosinase inhibiting activity of the conjugated inhibitor is still intact. Fell free contacting me if any problems appear or if you have any further questions.

Thank you Perret sir & Biersack Sir for your nice suggestions .Till now the synthesis is not complete within few days I will complete my synthetic work then I will study the apoptosis,confocal,FAX etc .If I will face any problem then I will contact you.

you could make use of gold metal attached to a biomimetic and coated with folate. you may want to choose biomimetic stable at a physiological pH but dissociate at lower pH. the pH of cancerous environment is usually acidic.

Thank you Oluyomi ,it is very helpful idea but problem with me is that how I can attach this moiety as a part of my PDT drug.I mean to say that as a ligand system in metal complex.Please suggest me some idea..

if you get a biomimetic linker with 2 arms so that folate is attached on one and the drug on other. u may want to use a thiol group, Au has affinity for -SH. You also need to activate your folate to be able to attach to biomimetic, depending on wat u are using.

Well, thiopropionate modified gold NPs have been applied to enhance the uptake of doxorubicin (builds a salt bridge with thiopropionate) into cancer cells. You could attach a suitable thiol-linker to your ferrocene-PDT which should react with gold NPs via the thio group.

Thank you both of you for your nice suggestions

Gold centers can also be placed into porphyrin systems leading to very active gold porphyrin complexes:

http://onlinelibrary.wiley.com/doi/10.1002/chem.200902741/abstract

http://cancerres.aacrjournals.org/content/70/1/329.abstract?sid=0f38eb71-9842-4693-9a0a-f6a404e55866

Thank you Bernhard Sir, these are really useful papers

Tumour cell often differ in the structure of cell surface markers present on them. These are known as 'Tumour associated glycopeptide antigens' and even though the difference in structure (of these cell surface markers) is not significant and invisible to our immune system, the information can be utilized for designing cancer vaccines. Often the glycopeptides antigens are over expressed in cancer cells.

The cancer cell over expresses certain ligand receptors than the normal cells for eg. lung cancer cells over expresses folate receptors than the normal cells, etc. For targeted photodynamic therapy you need to have a particular ligand attached to the material that will act for photodynamic therapy. Choosing a particular ligand for specific cancer cells is a crucial step for the targeted photodynamic therapy. I suggest you to attach folic acid to your compound if any amino linkage is present there in through carbodiimide chemistry. This folic acid functionalized compound then can be used for targeting lung cancer cell line.

I am new to this field,so can I know why Au is used rather than Cu metal nanoparticle for cancer cell targeting?I have seen some inorganic complexes of Cu which can be substituted for Cis-platin, so why not it could be used?