ICS84

Anti-cancer targeted drug delivery system comprising nir fluorescent switchable reporter based on xanthene-indolenine styryl dye

Ebaston T. M. Gary Gellerman Leonid Patsenker
Department of Chemical Sciences, Ariel University, Ariel, Israel

Targeted drug delivery (TDD) systems increase the therapeutic efficiency and reduce cytotoxic side effects. TDD systems equipped with a switchable fluorescent reporter, sensitive to drug release, enable real time monitoring of drug delivery in vitro and in vivo (Fig. A). We have developed and investigated novel TDD system OCT-HCy-CLB (Fig. B) comprising NIR switchable reporter based on xanthene-indolenine styryl dye HCy attached to an anticancer drug, chlorambucil (CLB), and targeting peptide octriotide (OCT). CLB is used to treat chronic lymphocytic leukemia. OCT is a cyclic S-S bridged octa-peptide (sandostatin) which targets overexpressed somatostatin receptors in tumor cells. The CLB was attached via cleavable ester linkage and OCT was attached via non-cleavable linker.

The release of CLB causes dramatic increase in fluorescence at ~710 nm (Fig. C). The time-dependent absorption and emission spectra of OCT-HCy-CLB in 10 mM phosphate buffer pH 7.4 (PB) and cell medium pH 7.4 (CM) were measured, the drug cleavage profiles were obtained (Fig. D), and the drug release rates were quantified by half-lives (t1/2). The CLB release from OCT-HCy-CLB measured in CM (half-life t1/2 ~ 30 min) was found to be about 4 fold faster compared to that in PB (half-life t1/2 ~ 2 h).

The obtained data indicate high potential of the developed platform for monitoring of TDD efficacy.

The work was supported by the Israel Scientific Foundation (ISF), project 810/18 and the KAMEA program (Leonid Patsenker).









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