[refurb]

I haven't dug into your papers to a great extent, but off the top of my head - you're injecting a biopolymer, followed by a modified chemotherapeutic agent. The chemotherapeutic agent then binds to the biopolymer.

In your one paper you test Doxorubicin, where the site of action is the tumor DNA itself. Presumably the biopolymer remains extracellular, so how does the "bound" Doxorubicin get to its active site?

Do you see Doxorubicin "unbinding" over time? Does the biopolymer itself enter the cell through phagocytosis?

[mejiaoneto]

Thank you for your comment.

Our approach increases the extracellular concentration of Dox and then it does the same job that it usually does.

[jcims]

Are there general strategies for adapting drugs to click-chemistry or is there something special about doxil that makes it amenable to this approach?

To me it seems like one upside of using a well known chemo agent is that the oncology community is going to be familiar with it and possibly more receptive to adopting it into their practice. Probably will help with the approval process too.

Is the delivery method a major aspect of the trial? Could the biopolymer be adjusted to also provide embolization and/or doped on some of the materials used for Y90/SIRSphere type targeted radiotherapy?

This really seems like a cool idea, I wish you and your team the best!

[mejiaoneto]

Thank you for your wishes.

Nothing special about doxorubicin. This is a broad technology that can be applied to many cancer therapies, including radionuclides as you as asked.

I agree with your comments on using a known agent.

[refurb]

Do you know the mechanism? Retro-Diels Alder?

[mejiaoneto]

That is correct. It is a retro diels alder reaction. Here is a link to an earlier report from us, that has the chemical structures: https://pubs.acs.org/doi/full/10.1021/acscentsci.6b00150