Ultracompact Nanotheranostic PEG Platform for Cancer Applications
journal contributionposted on 2018-09-19, 21:09 authored by Thomas Hopkins, Scott D. Swanson, Jeremy Damon Hoff, Natalie Potter, Rahil Ukani, Raoul Kopelman
We present a new targetable nanoconstruct (NC) capable of simultaneously serving as a therapeutic platform for photodynamic therapy (PDT) as well as a magnetic resonance (MR) molecular imaging agent, free of heavy metal atoms. PDT has seen much interest with the introduction of NC-assisted cell-specific targeting of the photosensitizer (PS). The previously reported ultrasmall 8-arm polyethylene glycol amine (8PEGA) NC, with an attached chlorin e6 (Ce6) PS, yielded promising results for PDT of heart arrhythmia, in vivo and ex vivo, on live rat and sheep hearts, respectively, when using targeting peptides for cell-specific ablation of cardio-myocytes. Here we explore the extension of this NC-based PDT to cancer. For this purpose, we switched the targeting peptide from CTP-cys to F3-cys. Notably, the 8PEGA-Ce6 NCs have a superior reactive oxygen species (ROS) production compared to traditional Ce6 encapsulated polyacrylamide (PAAm) NCs, which should be advantageous for PDT. This NC is also cyto-compatible and offers chemical flexibility for the attachment of a choice of targeting peptides. Finally, this label-free 8PEGA NC can be directly and selectively imaged by MRI, using standard spin–echo imaging sequences with large diffusion magnetic field gradients to suppress the water signal. Notably, due to its ultrasmall size this NC is also expected to have improved in vivo penetration and bioelimination, as was already shown in previous biodistribution studies.
Ultracompact Nanotheranostic PEG PlatformNC-assisted cell-specificpeptidesheep heartsMRIcell-specific ablationbiodistribution studiestargetable nanoconstructchemical flexibility8 PEGA-Ce 6 NCsPSROSheart arrhythmiavivo penetrationmetal atomswater signalreactive oxygen speciesF 3-cysMRultrasmall sizefield gradientsCe 6 encapsulated polyacrylamidechlorin e 6imaging agentlabel-free 8 PEGA NCphotodynamic therapyCancer ApplicationsNC-based PDT