A novel bacteriochlorin–styrylnaphthalimide conjugate for simultaneous photodynamic therapy and fluorescence imaging. Issue 44 (6th November 2017)

• Record Type: Journal Article
• Authors: Panchenko, Pavel A.; Grin, Mikhail A.; Fedorova, Olga A.; Zakharko, Marina A.; Pritmov, Dmitriy A.; Mironov, Andrey F.; Arkhipova, Antonina N.; Fedorov, Yuri V.; Jonusauskas, Gediminas; Yakubovskaya, Raisa I.; Morozova, Natalia B.; Ignatova, Anastasia A.; Feofanov, Alexey V.
• Is Part Of: Physical chemistry chemical physics. Volume 19:Issue 44(2017)
• Page Start: 30195
• Page End: 30206
• Publication Date: 2017-11-06
• Subjects: Chemistry, Physical and theoretical -- Periodicals; 541.3
• DOI: 10.1039/c7cp04449f
• Languages: English
• ISSNs: 1463-9076

Abstract

Abstract : The Photosensitizing and fluorescence imaging ability of a bacteriochlorin–naphthalimide conjugate is studied. Abstract : Propargyl-15 2, 17 3 -dimethoxy-13 1 -amide of bacteriochlorin e (BChl ) and a 4-(4- N, N -dimethylaminostyryl)- N -alkyl-1, 8-naphthalimide bearing azide group in the N -alkyl fragment were conjugated by the copper(i )-catalyzed 1, 3-dipolar cycloaddition to produce a novel dyad compoundBChl–NI for anticancer photodynamic therapy (PDT) combining the modalities of a photosensitizer (PS) and a fluorescence imaging agent. A precise photophysical investigation of the conjugate in solution using steady-state and time-resolved optical spectroscopy revealed that the presence of the naphthalimide (NI ) fragment does not decrease the photosensitizing ability of the bacteriochlorin (BChl ) core as compared withBChl ; however, the fluorescence of naphthalimide is completely quenched due to resonance energy transfer (RET) toBChl . It has been shown that theBChl–NI conjugate penetrates into human lung adenocarcinoma A549 cells, and accumulates in the cytoplasm where it has a mixed granular-diffuse distribution. BothNI andBChl fluorescence in vitro provides registration of bright images showing perfectly intracellular distribution ofBChl–NI . The ability ofNI to emit light upon excitation in imaging experiments has been found to be due to hampering of RET as a result of photodestruction of the energy acceptorBChl unit. Phototoxicity studies have shown that theBChl–NI conjugate is not toxic for A549 cells at tested concentrations (<8 μM) without light-induced activation. At the same time, the concentration-dependent killing of cells is observed upon the excitation of the bacteriochlorin moiety with red light that occurs due to reactive oxygen species formation. The presented data demonstrate that theBChl–NI conjugate is a promissing dual function agent for cancer diagnostics and therapy.