Show simple item record

dc.contributor.authorLiang, Barry J.
dc.contributor.authorLusvarghi, Sabrina
dc.contributor.authorAmbudkar, Suresh V.
dc.contributor.authorHuang, Huang Chiao
dc.date.accessioned2021-10-25T18:20:22Z
dc.date.available2021-10-25T18:20:22Z
dc.date.issued2021-07-26
dc.identifier.urihttp://hdl.handle.net/10713/16944
dc.description.abstractAccurate detection of ATP-binding cassette drug transporter ABCB1 expression is imperative for precise identification of drug-resistant tumors. Existing detection methods fail to provide the necessary molecular details regarding the functional state of the transporter. Photoimmunoconjugates are a unique class of antibody–dye conjugates for molecular diagnosis and therapeutic treatment. However, conjugating hydrophobic photosensitizers to hydrophilic antibodies is quite challenging. Here, we devise a photoimmunoconjugate that combines a clinically approved benzoporphyrin derivative (BPD) photosensitizer and the conformational-sensitive UIC2 monoclonal antibody to target functionally active human ABCB1 (i.e., ABCB1 in the inward-open conformation). We show that PEGylation of UIC2 enhances the BPD conjugation efficiency and reduces the amount of non-covalently conjugated BPD molecules by 17%. Size exclusion chromatography effectively separates the different molecular weight species found in the UIC2–BPD sample. The binding of UIC2–BPD to ABCB1 was demonstrated in lipidic nanodiscs and ABCB1-overexpressing triple negative breast cancer (TNBC) cells. UIC2–BPD was found to retain the conformation sensitivity of UIC2, as the addition of ABCB1 modulators increases the antibody reactivity in vitro. Thus, the inherent fluorescence capability of BPD can be used to label ABCB1-overexpressing TNBC cells using UIC2–BPD. Our findings provide insight into conjugation of hydrophobic photosensitizers to conformation-sensitive antibodies to target proteins expressed on the surface of cancer cells.en_US
dc.description.sponsorshipNational Science Foundationen_US
dc.description.urihttps://doi.org/10.1515/nanoph-2021-0252en_US
dc.language.isoenen_US
dc.publisherDe Gruyter Open Ltden_US
dc.relation.ispartofNanophotonicsen_US
dc.subjectABCB1en_US
dc.subjectbenzoporphyrin derivativeen_US
dc.subjectphotodynamic therapyen_US
dc.subjectphotoimmunoconjugateen_US
dc.subjectUIC2en_US
dc.titleUse of photoimmunoconjugates to characterize ABCB1 in cancer cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.1515/nanoph-2021-0252
dc.source.volume10
dc.source.issue12
dc.source.beginpage3049
dc.source.endpage3061


This item appears in the following Collection(s)

Show simple item record