Photodynamic enhancement of doxorubicin cytotoxicity

Lanks, Karl W.; Gao, Jianping; Sharma, Tarak

doi:10.1007/s002800050187

Cited by 6 publications

(10 citation statements)

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“…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%

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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%

“…We attribute this effect to the photodynamic damage of free DOX upon laser treatment. In contrast, DOX encapsulation into liposomes minimizes the direct photo-induced damage on DOX [30,41], suggesting that our formulation may have an advantage for cancer treatment.…”

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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“…After photoirradiation, the antiproliferative activity of each of ADM and TMPyP and their co-mixture was highly pronounced. The photoactivation of ADM yielded a photosensitization process mediated by the Photochemotherapy mediated by a tetracationic porphyrin and adriamycin increased generation of reactive oxygen species, superoxide, hydroxy radicals, and peroxide similar to that initiated by drug bioreduction [29]. Although ADM has the ability to photosensitize the formation of singlet oxygen, the quantum yield is very low ($0.02) [30].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the photosensitization process mediated by TMPyP is mainly by virtue of singlet oxygen [13,31]. It may be worthy to emphasize the role of singlet oxygen on the inactivation of the antioxidant enzymes, catalase and superoxide dismutase which block ADM cytotoxicity [29,32], as an additive factor for the increased photodynamic toxicity of TMPyP/ADM co-mixture.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the antitumor activity of combined photochemotherapy mediated by a meso-substituted tetracationic porphyrin and adriamycin

Kassab¹

2009

ABBS

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The combined anticancer modality comprising porphyrins as photodynamic sensitizers and anticancer drugs has been an interesting subject for many researchers. In this study, the photochemotherapeutic effect mediated by simultaneous photoactivation of tetracationic meso-tetrakis(N-methyl-4-pyridyl) porphine tetratosylate (TMPyP) and adriamycin (ADM) were explored using human hepatocellular carcinoma cell line (HePG2). The efficiency of TMPyP acting in concert with ADM in the dark and in the presence of photoirradiation was evaluated, by studying cell viability, caspase-3 activity and ultrastructural changes in the cells after incubation with each of the two agents, separately, or simultaneously as a co-mixture. Under dark conditions, the simultaneous incubation of cells with TMPyP and ADM significantly enhanced cell death by 1.8 folds and 1.3 folds, compared with TMPyP or ADM treatment, respectively. After photoirradiation, the antiproliferative effect of the co-treatment with TMPyP and ADM increased further by 2 folds. Transmission electron microscopy and the measurements of caspase-3 levels in treated cells revealed that the co-treatment of cells with ADM and TMPyP followed by light irradiation directed the cell death towards necrosis and abrogated the apoptotic cell death pathway, which was exhibited in cells treated with ADM in absence and in presence of photoirradiation.

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“…This suggests that DOX+Mce 6 and P-GFLG-DOX+P-GFLG-Mce 6 combinations produced similar cytotoxic intermediates with a concomitant enhancement of efficacy. Enhanced efficacy resulting from the combination of a photosensitizer and DOX has been demonstrated on various cell lines, such as Walker 256 carcinosarcoma cells (Edell and Cortese, 1988), H-MESO-1 human malignant mesothelioma cells (Brophy and Keller, 1992), murine L929 cells (Lanks et al, 1994), and murine hepatoma MH-22A (Kirveliene et al, 2006). SOS+DOX and P-GFLG-SOS+P-GFLG-DOX combinations also showed synergistic effects.…”

Section: In Vitro Growth Inhibition Of Agents In Combinationmentioning

confidence: 96%

Enhanced antitumor activity of combinations of free and HPMA copolymer-bound drugs

Hongrapipat

Kopečková

Prakongpan

et al. 2008

International Journal of Pharmaceutics

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The synergism in anticancer effect toward human renal carcinoma A498 cells by binary combinations of free and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound anticancer drugs, SOS thiophene (SOS), doxorubicin (DOX), and mesochlorin e 6 monoethylenediamine (Mce 6 ), was evaluated. The combination index (CI) analysis was used to quantify the synergism, antagonism, and additive effects. Both free drugs and HPMA copolymer conjugates, when used as single agents or in combination, exhibited cytotoxic activities against A498 cells, as determined using a modified MTT assay. As single agents, SOS and P-GFLG-SOS (HPMA copolymer conjugates containing SOS bound via glycylphenylalanylleucylglycine [GFLG] spacer) were significantly more effective than the other agents evaluated. The synergistic effects ranked in the order SOS+DOX>P-GFLG-DOX +P-GFLG-Mce 6 ≈DOX+Mce 6 >P-GFLG-SOS+P-GFLG-DOX≈SOS+Mce 6 >P-GFLG-SOS+P-GFLG-Mce 6 . The combination of SOS+DOX proved to be synergistic over all cell growth inhibition levels. All other combinations exhibited synergism in a wide range of drug effect levels. The SOS +Mce 6 and P-GFLG-SOS+P-GFLG-Mce 6 combinations displayed synergism up to drug affected fraction (f a ) values of about 0.8 and reached slight antagonism and nearly additivity at f a = 0.95, respectively. However, all other combinations were synergistic up to f a < 0.9 and were additive at higher f a values. The observations that most combinations produced synergistic effects will be important for clinical translation.

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Photodynamic enhancement of doxorubicin cytotoxicity

Cited by 6 publications

References 0 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

Evaluating the antitumor activity of combined photochemotherapy mediated by a meso-substituted tetracationic porphyrin and adriamycin

Enhanced antitumor activity of combinations of free and HPMA copolymer-bound drugs

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