Linker chemistry dictates the delivery of a phototoxic organometallic rhenium(i) complex to human cervical cancer cells from core crosslinked star polymer nanoparticles

Abstract

Release of a photoactive Re(i) complex from a polymer star via ketimine linkages gives improved phototoxicity.

Design and preclinical evaluation of nanostars for the passive pretargeting of tumor tissue

“…No-carrier-added fluorine-18 ( 18 F) was produced via an 18 O(p,n) 18 F nuclear reaction by bombarding enriched H 2 [ 18 O]O with 16.5-MeV protons using a GE PETtrace 880 cyclotron at MSKCC (New York, USA). Zirconium-89 ( 89 Zr) was produced via proton beam bombardment of yttrium foil and isolated as high purity [ 89 Zr]Zr-oxalate [34].…”

“…Radiochemical yields were calculated based on the decay-corrected radioactivity balance from the addition of the radioactivity to the reaction vial until completion of the synthesis. Radioactive samples were counted using a 2480 Wizard 2 automatic gamma counter (1 minute per measurement; 350-1300 keV for 18 F, 800-1000 keV for 89 Zr).…”

“…[ 18 F]F-Tz-PEG 11 -NODA and [ 18 F]F-Tz-NODA were produced and characterized according to protocols described previously [28]. Briefly, no-carrier-added 18 F was trapped on a preconditioned anion exchange cartridge (QMA sep-pak, Waters) and eluted with 0.4 M KHCO 3 . Metal-free glacial acetic acid was used to adjust the pH to 3.5-4, before adding a 2 mM AlCl 3 solution in 0.1 M NaOAc buffer (pH 4).…”

“…Total image volumes were cropped into individual image volumes using the Inveon Research Workspace software (Siemens Medical Solutions, Knoxville, USA). Counting rates in the reconstructed images were converted into activity concentrations (%ID/g) using a system calibration factor, derived from a mouse-sized waterequivalent phantom containing 18 F. Open source 3D Slicer software (v4.8.1) was used for further image processing. Three-dimensional volumes of interest (VOIs) were defined through semi-automatic segmentation techniques and activity concentrations were quantified by selecting the maximal uptake value per VOI.…”

“…We have recently demonstrated that polymeric nanostars can be used for effective passive delivery of cytotoxic compounds to cancer cells [17,18]. Nanostars, or star polymers, consist of linear polymer arms that are cross-linked at one end to form the core of the macromolecule.…”