We make polysaccharide nanoparticles for cancer treatment, they are efficiently transported into the cancerous cells even against concentration gradient, but they get stuck in endosomes / lysosomes, how to force them out? Nanoparticle diameter: 20-100 nm, depending on technology. Composition: polysaccharide (biodegradable-biocompatible, safe). Room temperature synthesis in water so we can encapsulate proteins, drug is covalently bound and released slowly. What type of drug shall we choose, we can use multiple drugs with synergetic effect, we can encapsulate proteins, RNA, various drugs that are normaly unable to pass cell membrane. We are open for cooperation.
How about combining your nanoparticles with Photodynamic Therapy? This works well for drugs such as doxorubicin, which also get sequestered into lysosomes. PDT disrupts the cellular membranes and allows these drugs to leak back out into the cell.
I'm also open to collaboration on this.
How about combining your nanoparticles with Photodynamic Therapy? This works well for drugs such as doxorubicin, which also get sequestered into lysosomes. PDT disrupts the cellular membranes and allows these drugs to leak back out into the cell.
I'm also open to collaboration on this.
In cell cultures we find that attaching cell penetrating peptides to our nanoparticles (gold) leads to free particles in the cytosol and even in the nucleus. This may be easy to try for your system, and it may work.
Look at the buffering capacity of your nano ps. cationic lipids will boost the lysosomal exit but it is conditional. There are various proteins involved on this whole process. Please refer to gaurav sahay's paper on nano particles. I hope this would help.
You could use drugs that burst lysosomes, such as GPN (glycylphenylalanine β-napthylamide). Bursting lysosomes can precipitate cell death, so you will have to distinguish between the effects of GPN treatment alone and cells with your particles + GPN treatment. If your particles were preferentially taken up by cancerous cells then anything that compromises the integrity of the lysosomal membrane, or blocks autophagosome formation, would presumably be of great value.
have you considered radiochemicals? no need to egt them out of the lysosomes in the first place. alpha emitting may be most attractive, but for a proof of concept 3H may be the simplest way.
check out fusogenic peptides, if you are using a sugar polymer you may be able to conjugate to surface, EDC coupling or load these short peptides inside your particle. They facilitate endo lyso escape, I know a group who has had good luck with them although the conjugate to surface of particle. But if you encapsulate them, as the particle disolutes in the lyso/endo, these peptides may do the job for you
Good luck!
cyclic RGD on the surface
check this:http://onlinelibrary.wiley.com/doi/10.1002/anie.200800357/full
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