In vitroevaluation and biodistribution of HER2-targeted liposomes loaded with an¹²⁵I-labelled DNA-intercalator

Abstract

The HER2-targeted liposomes possess the properties needed to bring about tumor-specific delivery and therapeutic effect of (125)I-Comp1.

Nuclisome—targeting the tumor cell nucleus

“…A similar high tumor-specific cell killing potential has been established also for HER2-targeted Nuclisome-particles [33]. Further, data collected verified a dose-response correlation compatible with that expected following high linear energy transfer irradiation.…”

“…By use of cellular assays that permitted quantification of the receptor-mediated uptake of the particles, we could confirm that the Nuclisome-particles are indeed taken up by the cultured cells through interaction with EGFR and HER2, respectively [32,33]. Importantly, the above studies showed that when receptors were blocked with an excess amount of free ligand, or liposomes were administered without targeting agent, the tumor-cell uptake was clearly suppressed.…”

“…The EGF-PEG-lipid and F5-PEG-lipid conjugates have subsequently been incorporated into liposomes composed of DSPC, cholesterol, and DSPE-PEG2000 (see e.g. [32,33]). Finally, the liposomes have been loaded with iodinated Comp1 using the pH-gradient-driven loading protocol which was first suggested by Mayer et al [34].…”

“…The in-vitro evaluation of the Nuclisome-particles has included confocal microscopy and autoradiography studies to verify that the radiolabeled drug, after cellular uptake of the particles, is set free in the cytoplasm and able to translocate to the cell nucleus [32,33]. showed that radioactive decays were co-localized with the nuclei of tumor cells [32], it appears plausible that 125 I causes an Auger effect on tumor-cell DNA.…”

“…The high specificity and remarkable potency make Nuclisome-particles interesting for NOTE: Mean doses are presented under the assumption of non-functional two-step targeting (no HER2 expression) and that the distribution of activity in the therapy study follows the biodistribution of HER2-targeting and non-targeting liposomes presented in Fondell et al [33]. [37]) of local ionizations (*) along tracks of an alpha particle, a beta particle and electrons from an Auger-electron emitter.…”