Can a nanocarrier of size 150 nm will help in delivering drug to tumor through EPR effect. I saw there are some literature even on 175 -200 nm nanoparticles those up taken by cells. Any concrete answer?
Any specific article in knowledge that specifically answer this issue?
Thank you for time!
Hi,
Please check this book chapter out
doi: 10.1007/978-94-017-8739-0_11
Also, check references 83, 84, and 91 in the pre-mentioned book chapter.
There are also some critical articles that show the limitations of EPR, including:
10.1016/j.jconrel.2014.03.057
10.1016/j.jconrel.2012.04.014
10.1158/0008-5472.CAN-12-4561
After reviewing this, there are 2 conclusions:
1- I think nanoparticles in the range of 20-200 nm may still work, just try to be as small as you can, because nanoparticles with average size of 200 nm has a size range of about 100-400 nm, depending on your PDI, so, a portion of your nanoparticles may not fall within the range of 20-200 nm.
2- depending on the type of tumors, uptake based on EPR may vary. Subcutaneous tumor xenografts have the most exaggerated prevalence of EPR, and probably nanoparticles as big as 200 nm can still work efficiently. However, orthotopic tumors are harder to approach by passive targeting (i.e. EPR) because of increased interstital fluid pressure (IFP). spontaneous tumors in genetically modified mice are the hardest to exhibit EPR and the EPR effect becomes widely variable.
Best
Youssef
You find lots of literature and, alas, lots of contrasting data.
In principle, if you stay below 200 nm you should be fine with EPR. But remember, it has to be 200 nm in the bloodstream, not in your glass tube. Always check the size in full culture medium or in presence of serum proteins. But size is not the only thing the counts in EPR. Youseff, above, came up with some nice references. He has the point about the kind of tumour and its localisation.
Simply said, EPR sounds cool but it's not as trivial as it seems.
And to add one more thing, size is important for extravasation. Once in proximity of the tumour, there are many other factors playing a role and size is probably the least important.
This is a very interesting question. There are three parameters which will determine the efficacy of tumor targeting namely 1) size of the nanoparticle; 2) half life of nanoparticles in blood and 3) penetration of nanoparticles in tumor (solid tumors have a high interstitial pressure).
The article attached below answers these questions very nicely. This article has been mentioned by George also. In principal, tumor accumulation of nanoparticles as a result of EPR depends upon its half life in blood and smaller the size of nanoparticle greater is the penetration throughout the tumor. The attached paper shows that 100 nm particles remain close to vasculature whereas 20 nm particles distribute throughout the tumor.
Also, as pointed out by Marco, particles should be non-fouling and this can be achieved by PEGylation.
http://pubs.acs.org/doi/full/10.1021/nl900031y
I think you have got the answers you need but here i would like to add one point. Different sized particles can enter the cells but before that it has to cross the tumour extra cellular matrix for that the recommended size is 50-100 nm. with this size it can penetrate through matrix and reach the tumor.
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