bcrp - publications

Predict more bcrp - ligand interactions now!

1. J Control Release. 2012 Feb 10. [Epub ahead of print]

Strongly amphiphilic photosensitizers are not substrates of the cancer stem cell
marker ABCG2 and provides specific and efficient light-triggered drug delivery of
an EGFR-targeted cytotoxic drug.

Selbo PK, Weyergang A, Eng MS, Bostad M, Mælandsmo GM, Høgset A, Berg K.

Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium
Hospital, Oslo University Hospital, Oslo, Norway; PCI Biotech AS, Lysaker,
Norway; Cancer Stem Cell Innovation Center (CAST-SFI), Institute for Cancer
Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

A wide range of anti-cancer drugs are substrates of the ATP-binding cassette
transporter ABCG2/CD338/BCRP/MXR, which is thought to play an important role in
multi-drug resistance (MDR) and protection of cancer stem cells (CSC) against
chemotherapeutics and photodynamic therapy (PDT). Hence, it is of importance to
develop drugs that are not substrates of ABCG2. The aim of this study was to
elucidate if photosensitizers utilized for the endo-lysosomal release drug
delivery method photochemical internalization (PCI) are substrates for ABCG2. The
breast carcinoma cell line MA11, with a Hoechst 33342 side population of >50% was
used as an ABCG2high model. The photosensitizer Pheophorbide A (PhA) and Hoechst
33342 were used as positive control substrates of ABCG2. ABCG2-inhibition by
fumitremorgin C (FTC) did neither induce an increased accumulation of three
different PCI-photosensitizers (di-sulfonated meso-tetraphenylporphine
(TPPS(2a)), di-sulfonated meso-tetraphenylchlorin (TPCS(2a)) and di-sulfonated
aluminium phtalocyanine (AlPcS(2a))) nor enhanced the photosensitization (P=0.65
for TPCS(2a)-PDT) of these PCI-based photosensitizers in the MA11 cells. The same
results were also obtained with TPPS(2a) in the malignant glioma cell line U87
having a SP of ~0.1%. In contrast, both uptake and PDT-induced cytotoxicity was
strongly enhanced for PhA when combined with FTC (P<0.001)). Specific and
efficient light-controlled killing of EGFR+/ABCG2+ MA11 cells was obtained by PCI
of the targeting toxin EGF-saporin. The novel data obtained in this study
demonstrates that strongly amphiphilic photosensitizers used for PCI-based drug
delivery are not substrates of ABCG2. This important findings warrant further
development of the PCI technology as a strategy for efficient and site-specific
eradication of MDR cells and CSC.

Copyright © 2012. Published by Elsevier B.V.

PMID: 22349185 [PubMed - as supplied by publisher]