Synergistic antiproliferative effect of chemo-phototherapy: Synthesis and photodynamic activity evaluation of novel Chlorin e6-artesunate conjugates as antiproliferative agents.

In order to increase the photodynamic effect of Chlorin e6, four Chlorin e6-artesunate conjugates were designed and synthesized. Among them, three conjugates (3, 6, 9) contained single artesunate side chain at 152, 173 and 131 of Chlorin e6, respectively, and one conjugate (11) contained three artesunate side chains. In the in vitro evaluation of photodynamic effect, the four conjugates showed more potent phototoxicity against HepG2 cells than Chlorin e6. The introduction of artesunate side chain significantly increased the intracellular ROS production, although the production of singlet oxygen was not improved. Compound 11 exhibited much more potent phototoxicity than the other conjugates because the three artesunate side chains greatly enhanced the ROS production and cellular uptake. The results demonstrated that the conjugation of Chlorin e6 and artesunate could accomplish synergistic effects of chemo-phototherapy, and finally enhanced their antiproliferative effects.

Guo X ，Wang L ，Wang S ，Li Y ，Cao L ，Cai R ，Zhao W ... -  《-》

Synthesis of novel Chlorin e6-curcumin conjugates as photosensitizers for photodynamic therapy against pancreatic carcinoma.

Curcumin (cur) has been comprehensively studied for its various biological properties, more precisely for its antitumor potential and it has shown the promising results as well. On the other hand, Chlorin e6 (Ce6) has mostly been used as a photosensitizer in photodynamic therapy (PDT) against a variety of carcinomas. In the present study, we have synthesized a series of Chlorin e6-curcumin (Ce6-cur) conjugates and investigated their photosensitizing potential against pancreatic cancer cell lines. All the synthesized compounds were characterized by UV, 1H NMR, 13C NMR and LC-MS. These Ce6-cur conjugates showed better physicochemical properties and higher singlet oxygen generation capability. The cellular uptake was studied in AsPC-1 cells using fluorescence-activated cell sorting (FACS). Compound 17 was rapidly internalized within 30 min and sustained for 24 h. Compound 17 showed excellent PDT efficacy with IC50 of 40, 35 and 41 nM against AsPC-1, MIA PaCa-2 and PANC-1 respectively with exceptional dark/phototoxicity ratio in the range of 2371-7500. Moreover, the treatment of compound 17 upregulated the expression of BAX, Cytochrome-C and cleaved caspase 9 while downregulating the Bcl-2 expression an anti-apoptotic protein marker. These results demonstrate outstanding capability of compound 17 as a potent photosensitizer which could improve the PDT efficacy in pancreatic cancer patients.

Jalde SS ，Chauhan AK ，Lee JH ，Chaturvedi PK ，Park JS ，Kim YW ... -  《-》

The photodynamic activity of 13(1)-[2'-(2-pyridyl)ethylamine] chlorin e(6) photosensitizer in human esophageal cancer.

A novel 131-pyridine substituted chlorin e6 derivative (Chlorin A) was synthesized. It has characteristic long wavelength absorption at 664 nm and the emission wavelength at 667 nm. The generation rate of singlet oxygen of this compound is higher than Temoporfin. In vitro, Chlorin A showed higher phototoxicity against the human esophageal cancer cells than Temoporfin while with lower dark-toxicity. Its accumulation effect in mitochondria, lysosomes and endoplasmic reticulum was traced in subcellular localization tests. In flow cytometry obvious apoptosis cells were observed after 2 h irradiation. Significant in vivo photodynamic anti-tumor efficacy was also exhibited on mice bearing esophageal cancer. So Chlorin A could be suggested as a promising anti-tumor drug candidate in photodynamic therapy.

Srdanović S ，Gao YH ，Chen DY ，Yan YJ ，Margetić D ，Chen ZL ... -  《-》

Anti-tumor evaluation of a novel methoxyphenyl substituted chlorin photosensitizer for photodynamic therapy.

Photodynamic therapy (PDT) is a non-invasive and innovative therapeutic approach which has been increasingly applied in clinical cancer therapy. As the central element of PDT, the development of novel photosensitizers (PSs) with longer absorption wavelength, proper lipophilic/hydrophilic profiles, target tissue selectivity, and higher photo-/lowest dark-cytotoxicity is a challenging task. Previously, we designed and synthesized a series of novel long-wavelength chlorin e6 (Ce6)-based PSs via introducing aromatic groups to the vinyl of Ce6 skeleton. The new formed compounds with π-extension system exhibited improved photodynamic effects and spectral characteristics. Among these π-conjugated chlorin PSs, (E)-32-(4-methoxyphenyl)-chlorin e6, named A15, was expected to be a potent antitumor candidate as a PDT agent due to its good photobiological properties. Herein, in this work, we evaluated the effectiveness of A15 in cancer PDT. In vitro, a novel rare earth probe, ATTA-Eu3+ was applied to detect the singlet oxygen (1O2) production of A15 in solution and human hepatoma HepG2 cells, respectively. Moreover, A15 exhibited strong phototoxicity and weak dark cytotoxity to HepG2 cells. In H22 tumor bearing mice, A15 showed excellent tumor accumulation ability via i.v. administration and induced tumor regression, followed by laser treatment. These results indicated that A15 is a potential novel π-extension chlorin-type PS for PDT applications.

Dong Y ，Li G ，Wang L ，Cao L ，Li Y ，Zhao W ... -  《-》

Chlorin p6-Based Water-Soluble Amino Acid Derivatives as Potent Photosensitizers for Photodynamic Therapy.

Meng Z ，Yu B ，Han G ，Liu M ，Shan B ，Dong G ，Miao Z ，Jia N ，Tan Z ，Li B ，Zhang W ，Zhu H ，Sheng C ，Yao J ... -  《-》