- A near-infrared and lysosomal targeting thiophene-BODIPY photosensitizer: Synthesis and its imaging guided photodynamic therapy of cancer cells
-
In this study, a novel NIR and lysosomal targeting thiophene-BODIPY photosensitizer SBOP-Lyso was synthesized to explore its potential applications in photodynamic therapy of A549 cells. In the strategy of designing SBOP-Lyso, S atom in thiophene as well as heavy atom I were introduced to promote ISC efficiency to ensure high singlet oxygen yield. A common lysosome targeted group (M1: 1-(2-morpholinoethyl)-1H-indole-3-carbaldehyde) was linked to SBOP to extend its wavelength to the NIR region. Its absorption peak was at 660 nm (εmax = 5.2 × 104 cm?1 M?1) and its corresponding emission peak was located at 705 nm. Singlet oxygen could be quickly generated by SBOP-Lyso in the presence of 660 nm LED irradiation and the singlet oxygen yield was up to 44.1%. In addition, it also had good biocompatibility and could enter cells or zebrafish in a short time. SBOP-Lyso had negligible dark cytotoxicity (cell survival rate > 80%) and excellent phototoxicity (IC50 = 0.2 μM). DCFH-DA (ROS indicator) proved that SBOP-Lyso could generate singlet oxygen with 660 nm LED irradiation. Singlet oxygen produced by SBOP-Lyso could kill cancer cells in PDT process and it had the ability to effectively inhibit A549 cells migration. Besides that, lysosomal colocalization assay showed that it had good lysosomal localization ability (Pearson colocation coefficient, R = 0.93). Considering the above results, SBOP-Lyso as a unique lysosome-targeted photosensitizer with excellent properties would exhibit positive results in PDT process of cancer cells.
- Bai, Jin,Zhang, Lei,Qian, Ying
-
-
Read Online
- A novel carbazolyl GFP chromophore analogue: Synthesis strategy and acidic pH-activatable lysosomal probe for tracing endogenous viscosity changes
-
Intracellular viscosity changes of the internal microenvironment lead to many diseases, including cancer, inflammation, and neurodegenerative diseases. A novel, acidic pH-activatable carbazolyl GFP chromophore analogue,Lys-CzFP, was designed for tracing lysosomal viscosity changes. The developed synthesis is an efficient, novel, one-pot procedure.Lys-CzFPserves as a fluorescent molecular rotor and the internal carbazole and benzazole moieties ofLys-CzFPserve as rotators, which can rotate around the single C-C bond in the π-conjugated bridge.Lys-CzFPshowed a long emission wavelength at 560 nm and a large Stokes shift of 78 nm. The fluorescence intensity ofLys-CzFPexhibited a significant enhancement with increasing viscosity. The fluorescence intensity increased by 98-fold within 5 s from 1.0 cP to 1412 cP, while the fluorescence quantum yield (?F) increased from 0.003 to 0.253 and the fluorescence lifetime increased from 0.25 ns to 1.12 ns, respectively. Furthermore, interference experiments indicated thatLys-CzFPcould particularly respond to viscosity. Additionally,Lys-CzFPhad excellent biocompatibility, low cytotoxicity, and lysosomal localization. Finally,Lys-CzFPwas successfully applied to tracing endogenous viscosity changes in living cells.
- Qian, Ying,Shen, Baoxing,Zhi, Xu
-
-
Read Online
- Novel indole-BODIPY photosensitizers based on iodine promoted intersystem crossing enhancement for lysosome-targeted imaging and photodynamic therapy
-
In this work, we report the new lysosome-targeting indole-BODIPY derivatives BDP-Lys, IBDP-Lys, and I2BDP-Lys. BDP-Lys dye was designed for fluorescence imaging through introduction of an indole-containing morpholine moiety to a BODIPY core. Monoiodine and diiodine were incorporated into BDP-Lys dye to develop the photosensitizers IBDP-Lys and I2BDP-Lys. The maximum absorption (λabs) for IBDP-Lys and I2BDP-Lys displayed a redshift at approximately 11 nm and 27 nm, respectively, compared with the BDP-Lys dye (λabs= 504 nm). Similarly, the maximum emission also exhibited a redshift. The fluorescence quantum yield (ΦF) of IBDP-Lys (ΦF= 0.37%) and I2BDP-Lys (ΦF= 0.71%) was much lower than that of BDP-Lys dye (ΦF= 7.48%). The singlet oxygen quantum yields were measured as 43.10% for IBDP-Lys and 71.00% for I2BDP-Lys, which were higher than the iodine-free dye BDP-Lys. The theoretical calculation reasonably explains that iodine atoms promoted the intersystem crossing (ISC) process, and di-iodine further enhanced the ISC in indole-BODIPY dyes. Moreover, monoiodine photosensitizer IBDP-Lys was able to balance the generation of singlet oxygen and biocompatibility in cancer treatment. IBDP-Lys exhibited low dark toxicity (cell viability >90%), satisfactory biocompatibility, and precise lysosome targeting, with a Pearson coefficient of 0.93. The IBDP-Lys photosensitizer also was able to kill tumour cells. Considering the above results, the novel structure of indole-BODIPY photosensitizers could serve as a potential platform for lysosome-targeted imaging and photodynamic therapy.
- Liu, Miao,Wang, Chengjun,Qian, Ying
-
supporting information
p. 18082 - 18089
(2021/10/12)
-
- Design, synthesis and biological evaluation of a series of pyrano chalcone derivatives containing indole moiety as novel anti-tubulin agents
-
A new series of pyrano chalcone derivatives containing indole moiety (3-42, 49a-49r) were synthesized and evaluated for their antiproliferative activities. Among all the compounds, compound 49b with a propionyloxy group at the 4-position of the left phenyl ring and N-methyl-5-indoly on the right ring displayed the most potent cytotoxic activity against all tested cancer cell lines including multidrug resistant phenotype, which inhibits cancer cell growth with IC50 values ranging from 0.22 to 1.80 μM. Furthermore, 49b significantly induced cell cycle arrest in G2/M phase and inhibited the polymerization of tubulin. Molecular docking analysis demonstrated the interaction of 49b at the colchicine binding site of tubulin. In experiments in vivo, 49b exerted potent anticancer activity in HepG2 human liver carcinoma in BALB/c nude mice. These results indicated these compounds are promising inhibitors of tubulin polymerization for the potential treatment of cancer.
- Wang, Guangcheng,Li, Chunyan,He, Lin,Lei, Kai,Wang, Fang,Pu, Yuzi,Yang, Zhuang,Cao, Dong,Ma, Liang,Chen, Jinying,Sang, Yun,Liang, Xiaolin,Xiang, Mingli,Peng, Aihua,Wei, Yuquan,Chen, Lijuan
-
p. 2060 - 2079
(2014/04/17)
-
- Synthesis and pharmacological evaluation of analogs of indole-based cannabimimetic agents
-
Aminoalkylindoles (AAIs), although structurally dissimilar from the classical cannabinoids, are known to be capable of binding to cannabinoid receptors and of evoking cannabinomimetic responses. With the aim of investigating the structure-activity relationships (SAR) for the binding of non-classical agonists to CB1 and CB2 cannabinoid receptors, we designed and synthesized a series of indole derivatives. The compounds were tested for their analgesic action by formalin test and compared to WIN 55212-2, an AAI acting to the cannabinoid receptors. In receptor binding assay, compound 5 showed affinity for the CB1 receptor comparable to WIN 55212-2.
- Mazzoni, Orazio,Diurno, Maria V.,Di Bosco, Antonio M.,Novellino, Ettore,Grieco, Paolo,Esposito, Giovanni,Bertamino, Alessia,Calignano, Antonio,Russo, Roberto
-
experimental part
p. 106 - 114
(2010/11/03)
-