Mechanism of action and spectrum of cell types susceptible to doxorubicin photochemotherapy

Gao, Jianping; Lanks, Karl W.; Rosen, Martin H.; Lai, Bai-Tang

doi:10.1007/s002800050638

Cited by 6 publications

(14 citation statements)

References 7 publications

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“…To demonstrate that these liposomes may serve as promising candidates for light-triggered release applications in vivo , we rationalized that cell-compatible wavelengths (such as visible or Near Infra Red (NIR)) in combination with an appropriate photosensitizer are likely to produce modifications in the diacetylene groups necessary for release of entrapped contents [5,30]. Our first experiments towards this effort were designed to establish the ability of visible light source(s) to promote leakage of liposome-entrapped molecules.…”

Section: Resultsmentioning

confidence: 99%

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A novel class of photo-triggerable liposomes containing DPPC:DC8,9PC as vehicles for delivery of doxorubcin to cells

Yavlovich

Singh

Blumenthal

et al. 2011

Biochimica et Biophysica Acta (BBA) - Biomembranes

118

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Success of nanoparticle-mediated drug delivery is subject to development of optimal drug release strategies within defined space and time (triggered release). Recently, we reported a novel class of photo-triggerable liposomes prepared from dipalmitoyl phosphatidylcholine (DPPC) and photopolymerizable diacetylene phospholipid (DC8,9PC), that efficiently released entrapped calcein (a water soluble fluorescent dye) upon UV (254 nm) treatment. To develop these formulations for in vivo applications, we have examined phototriggering of these liposomes by visible light, and the effect of released anticancer drugs on cellular toxicity. Sonicated liposomes containing various ratios of DPPC:DC8,9PC and 4 mol% DSPE-PEG2000 were loaded with calcein (Ex/Em, 485/517 nm) or a chemotherapy drug, Doxorubicin (DOX, Ex/Em 490/590 nm). Our initial experiments showed that 514 nm laser treatment of liposomes containing 10 or 20 mol% DC8,9PC for 1–3 minutes resulted in significant release of calcein. Based on these results, we performed studies with DOX-loaded liposomes. First, biophysical properties (including liposome size and stability) and DOX encapsulation efficiency of the liposomes were determined. Subsequently, the effect of 514 nm laser on DOX release, and cellular toxicity by released DOX were examined. Since liposomes using the 86:10:04 mole ratio of DPPC:DC8,9PC:DSPE-PEG2000, showed highest encapsulation of DOX, these formulations were investigated further. We report that (i) Liposomes retained about 70% of entrapped DOX at 37°C in the presence of 0–50% serum. (ii) 514 nm laser treatment resulted in DOX release from liposomes in a wavelength specific manner. (iii) Laser treatment of co-cultures containing DOX-loaded liposomes and cells (Raji and MCF-7) resulted in at least 2–3 fold improved cell-killing as compared to untreated samples. Taken together, the phototriggerable liposomes described here may provide a platform for future drug delivery applications. To our knowledge, this is the first report demonstrating improved cell killing following light-triggered release of an encapsulated anticancer agent from photosensitive liposomes.

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Section: Resultsmentioning

confidence: 99%

“…Previous studies show that free DOX is prone to photodynamic damage when exposed to laser, and intracellular accumulation of DOX minimizes this photo-induced damage [30,41]. Therefore, it was important to examine the biological activity of free DOX in our experimental set up.…”

Section: Resultsmentioning

confidence: 99%

A novel class of photo-triggerable liposomes containing DPPC:DC8,9PC as vehicles for delivery of doxorubcin to cells

Yavlovich

Singh

Blumenthal

et al. 2011

Biochimica et Biophysica Acta (BBA) - Biomembranes

118

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“…Many groups reported quantitative differences in the long-term cytotoxic effects among anthracyclines (Andreoni et al, 1991a,b potency, however, was shown to depend on the cell line (Gao et al, 1997). Cell lines (B14 and NIH 3T3) investigated in this work differed considerably in their dose responses to aclarubicin and mitoxantrone so that the cytotoxicity of mitoxantrone was greater by an order of magnitude than cytotoxicity of aclarubicin.…”

Section: Discussionmentioning

confidence: 75%

“…Poor response to PDT was observed for doxorubicin concentrations and laser power density less than the relevant threshold values (Gao et al, 1997;Lanks et al, 1994). These results suggest that to achieve significant enhancement of drug cytotoxicity it is necessary to exceed the threshold power density and the duration time of irradiation attributed to the particular cell line.…”

Section: Discussionmentioning

confidence: 85%

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Combined effect of low-power laser irradiation and anthraquinone anticancer drug aclarubicin on survival of immortalized cells: Comparison with mitoxantrone

Koceva‐Chyła¹,

Więcławska²,

Jóźwiak³

et al. 2006

Cell Biology International

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The photodynamic response of the anthraquinone anticancer drug aclarubicin (ACL) was investigated in vitro and compared with that of mitoxantrone (MTX). Cultured immortalized rodent B14 and NIH 3T3 cells were used in the experiments as a model for cells with neoplastic phenotype. Long-term cytotoxicity and inhibition of cell proliferation assayed by the clonal growth and MTT-tetrazolium methods were estimated to compare the efficacy of aclarubicin and mitoxantrone in photosensitizing cells and their death after non-thermal exposure to monochromatic laser light. Green He-Ne (543.5 nm) or red semiconductor (670 nm) low-power laser (LPL) irradiations were applied. Different dose-responses of both cell lines to aclarubicin and mitoxantrone were found so that the cytotoxicity of MTX was considerably greater than the cytotoxicity of ACL. Phototherapy response (P < 0.0001) was observed only for B14 cells after sensitisation with aclarubicin. Under the same conditions no significant effect of red light irradiation (semiconductor 670 nm laser) on survival of both cell lines treated with mitoxantrone was found.

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Ultrafast Electron Transfer in Complexes of Doxorubicin with Human Telomeric G‐Quadruplexes and GC Duplexes Probed by Femtosecond Fluorescence Spectroscopy

et al. 2016

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Doxorubicin (DOX) is a natural anthracycline widely used in chemotherapy; its combined application as a chemotherapeutic and photodynamic agent has been recently proposed. In this context, understanding the photoinduced properties of DOX complexes with nucleic acids is crucial. Herein, the study of photoinduced electron transfer in DOX-DNA complexes by femtosecond fluorescence spectroscopy is reported. The behaviour of complexes with two model DNA structures, a G-quadruplex (G4) formed by the human telomeric sequence (Tel21) and a d(GC) duplex, is compared. The DOX affinity for these two sequences is similar. Although both 1:1 and 2:1 stoichiometries have been reported for DOX-G4 complexes, only 1:1 complexes form with the duplex. The steady-state absorption indicates a strong binding interaction with the duplex due to drug intercalation between the GC base pairs. In contrast, the interaction of DOX with Tel21 is much weaker and arises from drug binding on the G4 external faces at two independent binding sites. As observed for DOX-d(GC) complexes, fluorescence of the drug in the first binding site of Tel21 exhibits decays within a few picoseconds following a biphasic pattern; this is attributed to the existence of two drug conformations. The fluorescence of the drug in the second binding site of Tel21 shows slower decays within 150 ps. These timescales are consistent with electron transfer from the guanines to the excited drug, as favoured by the lower oxidation potential of the stacked guanines of G4 with respect to those in the duplex.

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Mechanism of action and spectrum of cell types susceptible to doxorubicin photochemotherapy

Cited by 6 publications

References 7 publications

A novel class of photo-triggerable liposomes containing DPPC:DC8,9PC as vehicles for delivery of doxorubcin to cells

A novel class of photo-triggerable liposomes containing DPPC:DC8,9PC as vehicles for delivery of doxorubcin to cells

Combined effect of low-power laser irradiation and anthraquinone anticancer drug aclarubicin on survival of immortalized cells: Comparison with mitoxantrone

Ultrafast Electron Transfer in Complexes of Doxorubicin with Human Telomeric G‐Quadruplexes and GC Duplexes Probed by Femtosecond Fluorescence Spectroscopy

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