Co-reporter:Mei-Rong Ke, Shao-Fang Chen, Xiao-Hui Peng, Qiao-Feng Zheng, Bi-Yuan Zheng, Chih-Kuang Yeh, Jian-Dong Huang
European Journal of Medicinal Chemistry 2017 Volume 127(Volume 127) pp:
Publication Date(Web):15 February 2017
DOI:10.1016/j.ejmech.2016.12.056
•A novel phthalocyanine-tetrapeptide-doxorubicin prodrug has been synthesized.•Both photosensitizing activity and cytotoxicity of the conjugate are inhibited.•It can be activated by fibroblast activation protein both in vitro and in vivo.•The prodrug shows a synergistic anticancer efficacy against HepG2 cells.Chemo-photodynamic therapy is a promising strategy for cancer treatments. However, it remains a challenge to develop a chemo-photodynamic therapeutic agent with little side effect, high tumor-targeting, and efficient synergistic effect simultaneously. Herein, we report a zinc(II) phthalocyanine (ZnPc)-doxorubicin (DOX) prodrug linked with a fibroblast activation protein (FAP)-responsive short peptide with the sequence of Thr-Ser-Gly-Pro for chemo-photodynamic therapy. In the conjugate, both photosensitizing activity of ZnPc and cytotoxicity of DOX are inhibited obviously. However, FAP-triggered separation of the photosensitizer and DOX can enhance fluorescence emission, singlet oxygen generation, dark- and photo-cytotoxicity significantly, and lead to a synergistic anticancer efficacy against HepG2 cells. The prodrug can also be specifically and efficiently activated in tumor tissue of mice. Thus, this prodrug shows great potential for clinical application in chemo-photodynamic therapy.Download high-res image (329KB)Download full-size image
Co-reporter:Dong-Hua Wan;Bi-Yuan Zheng;Mei-Rong Ke;Ji-Ying Duan;Yun-Quan Zheng;Chih-Kuang Yeh;Jian-Dong Huang
Chemical Communications 2017 vol. 53(Issue 29) pp:4112-4115
Publication Date(Web):2017/04/06
DOI:10.1039/C6CC09541K
C-Phycocyanin (CPC) as a tumour-associated macrophage (TAM)-targeted photosensitiser has been first proved, and used as a vehicle of zinc phthalocyanine (ZnPc) to fabricate a ZnPc–CPC conjugate, which exhibits an efficient in vitro photodynamic activity, and selectively accumulates in tumour sites probably due to the affinity to TAM.
Co-reporter:Xiao-Hui Peng, Shao-Fang Chen, Bi-Yuan Zheng, Bing-De Zheng, Qiao-Feng Zheng, Xing-Shu Li, Mei-Rong Ke, Jian-Dong Huang
Tetrahedron 2017 Volume 73(Issue 4) pp:378-384
Publication Date(Web):26 January 2017
DOI:10.1016/j.tet.2016.12.017
•Two novel phthalocyanine-CLB conjugates (5 and 7) have been synthetized.•The structure-activity relationships of these compounds have been discussed.•6 and 7 show weaker singlet oxygen generation efficiency than that of 4 and 5.•Compound 6 shows the highest photocytotoxicity against HepG2 cells (IC50 = 9 nM).Two amine-terminated phthalocyanines, including mono-α-substituted zinc phthalocyanine (ZnPc) 4 and axially di-substituted silicon phthalocyanine (SiPc) 6, as well as their chlorambucil (CLB) conjugates (5 and 7) have been prepared. Both 4 and 6 show very high photocytotoxicities against HepG2 cells with IC50 values down to 31 nM and 9 nM, respectively. However, after conjugating with CLB, the anticancer activities of both conjugates, ZnPc-CLB 5 (IC50 = 0.20 μM) and SiPc-CLB 7 (IC50 = 17.47 μM), are greatly reduced as a result of their lower efficiency in fluorescence emission and singlet oxygen generation in aqueous solution. Moreover, both conjugates show significantly lower cellular uptake than their precursors, 4 and 6. Synergetic chemo-photodynamic therapy could not be observed on the two conjugates.
Co-reporter:Wen-Liang Lan, Feng-Ran Liu, Mei-Rong Ke, Pui-Chi Lo, Wing-Ping Fong, Dennis K.P. Ng, Jian-Dong Huang
Dyes and Pigments 2016 Volume 128() pp:215-225
Publication Date(Web):May 2016
DOI:10.1016/j.dyepig.2016.01.031
•Three ZnPcs substituted with sulfonated quinolineoxy groups have been synthesized.•Their photocytotoxicities under different formulations have been examined.•The structure–activity relationships of these compounds have been discussed.Three zinc(II) phthalocyanines substituted with sulfonated quinolineoxy groups, including the mono-α-substituted 1, tetra-α-substituted 3, and tetra-β-substituted 4 were synthesized and characterized. These compounds (in deprotonated form) were water-soluble and could be formulated with Cremophor EL or phosphate buffered saline. When formulated with phosphate buffered saline, the serum albumin exerted an important effect on the aggregation tendency and spectroscopic properties of these compounds in biological media. In the case of phosphate buffered saline formulation, the photocytotoxicity followed the order 3 > 4 >> 1 for both human colon carcinoma HT29 and human hepatocarcinoma HepG2 cell lines as a result of their different aggregation tendency. Interestingly, when formulated with Cremophor EL, 1 showed the highest photocytotoxicity not only due to its highest cellular uptake but also due to the reduced aggregation. In both of these formulated systems, the tetra-α-substituted compound 3 exhibited a higher potency than the tetra-β-substituted analogue 4.
Co-reporter:Bi-Yuan Zheng, Mei-Rong Ke, Wen-Liang Lan, Lu Hou, Jun Guo, Dong-Hua Wan, Ling-Zhi Cheong, Jian-Dong Huang
European Journal of Medicinal Chemistry 2016 Volume 114() pp:380-389
Publication Date(Web):23 May 2016
DOI:10.1016/j.ejmech.2016.02.066
•A series of ZnPcs substituted with morpholineyl moieties have been synthesized.•The structure-activity relationships of these compounds have been discussed.•The cellular uptake and photocytotoxicity increased after quaternization.•The cationic ZnPc 6a shows the highest photocytotoxicity against C. albicans.A series of zinc(II) phthalocyanines (ZnPcs) mono-substituted and tetra-substituted with morpholinyl moieties and their quaternized derivatives have been synthesized and evaluated for their antifungal photodynamic activities toward Candida albicans. The α-substituted, quaternized, and mono-substituted ZnPcs are found to have higher antifungal photoactivity than β-substituted, neutral, and tetra-substituted counterparts. The cationic α-mono-substituted ZnPc (6a) exhibits the highest photocytotoxicity. Moreover, it is more potent than axially di-substituted analogue. The different photocytotoxicities of these compounds have also been rationalized by investigating their spectroscopic and photochemical properties, aggregation trend, partition coefficients, and cellular uptake. The IC90 value of 6a against C. albicans cells is as low as 3.3 μM with a light dose of 27 J cm−2, meaning that 6a is a promising candidate as the antifungal photosensitizer for future investigations.
Co-reporter:Bi-Yuan Zheng, Xiao-Min Shen, Dong-Mei Zhao, Yi-Bin Cai, Mei-Rong Ke, Jian-Dong Huang
Journal of Photochemistry and Photobiology B: Biology 2016 Volume 159() pp:196-204
Publication Date(Web):June 2016
DOI:10.1016/j.jphotobiol.2016.03.055
•A series of SiPcs substituted with nucleoside moieties have been synthetized.•The structure–activity relationships of these compounds have been discussed.•The guanosine-substituted SiPc shows a weak singlet oxygen generation efficiency.•The monochloro-adenosine-substituted SiPc exhibits the highest photocytotoxicity.A series of new silicon(IV) phthalocyanines (SiPcs) di-substituted axially with different nucleoside moieties have been synthesized and evaluated for their singlet oxygen quantum yields (ΦΔ) and in vitro photodynamic activities. The adenosine-substituted SiPc shows a lower photosensitizing efficiency (ΦΔ = 0.35) than the uridine- and cytidine-substituted analogs (ΦΔ = 0.42–0.44), while the guanosine-substituted SiPc exhibits a weakest singlet oxygen generation efficiency with a ΦΔ value down to 0.03. On the other hand, replacing axial adenosines with chloro-modified adenosines and purines can result in the increase of photogenerating singlet oxygen efficiencies of SiPcs. The formed SiPcs 1 and 2, which contain monochloro-modified adenosines and dichloro-modified purines respectively, appear as efficient photosensitizers with ΦΔ of 0.42–0.44. Both compounds 1 and 2 present high photocytotoxicities against HepG2 and BGC823 cancer cells with IC50 values ranging from 9 nM to 33 nM. The photocytotoxicities of these two compounds are remarkably higher than the well-known anticancer photosensitizer, chlorin e6 (IC50 = 752 nM against HepG2 cells) in the same condition. As revealed by confocal microscopy, for both cell lines, compound 1 can essentially bind to mitochondria, while compound 2 is just partially localized in mitochondria. In addition, the two compounds induce cell death of HepG2 cells likely through apoptosis.Four novel silicon(IV) phthalocyanines substituted axially with different nucleoside moieties have been synthesized. The two chlorine-containing compounds 1 and 2 show extremely high photocytotoxicity against HepG2 and BGC823 cancer cells and can induce HepG2 cell death mainly through apoptosis. The photocytotoxicities of both compounds are remarkably higher than the well-known anticancer photosensitizer, chlorin e6.
Co-reporter:Hai-Jun Chen, Xiu-Rong Huang, Xiao-Bin Zhou, Bi-Yuan Zheng and Jian-Dong Huang
Chemical Communications 2015 vol. 51(Issue 22) pp:4681-4684
Publication Date(Web):06 Feb 2015
DOI:10.1039/C5CC00927H
The potential application of artemether as a novel sonosensitizer for sonodynamic therapy (SDT) was explored and illustrated for the first time. In addition, liposome-encapsulated artemether exhibited significantly enhanced sonodynamic anticancer activity. Our findings indicated that artemisinin derivatives may serve as a new kind of sonosensitizer for SDT.
Co-reporter:Xing-Shu Li, Mei-Rong Ke, Miao-Fen Zhang, Qing-Qing Tang, Bi-Yuan Zheng and Jian-Dong Huang
Chemical Communications 2015 vol. 51(Issue 22) pp:4704-4707
Publication Date(Web):11 Feb 2015
DOI:10.1039/C4CC09934F
A novel zinc(II) phthalocyanine bearing octa-sulphonates has been prepared, which is non-aggregated in water, highly photoactive and low dark-toxic. More interestingly, it exhibits specific affinity to macrophages via the scavenger receptor-A, and can selectively accumulate in tumour sites.
Co-reporter:He-Nan Xu, Hai-Jun Chen, Bi-Yuan Zheng, Yun-Quan Zheng, Mei-Rong Ke, Jian-Dong Huang
Ultrasonics Sonochemistry 2015 Volume 22() pp:125-131
Publication Date(Web):January 2015
DOI:10.1016/j.ultsonch.2014.05.019
•A non-covalent BSA conjugate of ZnPcC4 (ZnPcC4–BSA) was prepared.•ZnPcC4 and ZnPcC4–BSA exhibited sonodynamic activities against HepG2 cells.•ZnPcC4–BSA showed a higher sonodynamic activity.•The albumin conjugates of ZnPcs can serve as promising sonosensitizers for SDT.Sonodynamic therapy (SDT) is a new approach for cancer treatment, involving the synergistic effect of ultrasound and certain chemical compounds termed as sonosensitizers. A water-soluble phthalocyanine, namely tetra-α-(3-carboxyphenoxyl) zinc(II) phthalocyanine (ZnPcC4), has been prepared and characterized. The interactions between ZnPcC4 and bovine serum albumin (BSA) were also investigated by absorption and fluorescence spectroscopy. It was found that there were strong interactions between ZnPcC4 and BSA with a binding constant of 6.83 × 107 M−1. A non-covalent BSA conjugate of ZnPcC4 (ZnPcC4–BSA) was prepared. Both ZnPcC4 and ZnPcC4–BSA exhibited efficient sonodynamic activities against HepG2 human hepatocarcinoma cells. Compared with ZnPcC4, conjugate ZnPcC4–BSA showed a higher sonodynamic activity with an IC50 value of 7.5 μM. Upon illumination with ultrasound, ZnPcC4–BSA can induce an increase of intracellular reactive oxygen species (ROS) level, resulting in cellular apoptosis. The results suggest that the albumin conjugates of zinc(II) phthalocyanines functionalized with carboxyls can serve as promising sonosensitizers for sonodynamic therapy.
Co-reporter:Bi-Yuan Zheng, Xiong-Jie Jiang, Tao Lin, Mei-Rong Ke, Jian-Dong Huang
Dyes and Pigments 2015 Volume 112() pp:311-316
Publication Date(Web):January 2015
DOI:10.1016/j.dyepig.2014.07.029
•A series of SiPcs axially substituted with piperidinyl moieties has been synthesized.•The structure–activity relationships of these compounds has been discussed.•The methylation of piperidinyl groups can enhance the photosensitizing activities.•The cellular uptake toward C. albicans decreased after the methylation.•One of cationic compounds shows the highest photocytotoxicity against C. albicans.A new series of silicon(IV) phthalocyanines (SiPcs) axially di-substituted with piperidinyl moieties (compounds 1, 2a, and 3a) and their N-methylated derivatives (compounds 2b and 3b) have been synthesized and characterized. Meanwhile, an analogue di-substituted with cyclohexyl groups (compound 4) has also been prepared as a control. The antifungal photoactivities of these SiPcs toward Candida albicans were found to follow the order: 2b ＞ 3a ≈ 3b ＞ 1 ≈ 2a ＞ 4. The structure–activity relationship of these phthalocyanines has been discussed by investigating their photophysical and photochemical properties, partition coefficient, and cellular uptake. The cationic phthalocyanine 2b shows the highest photodynamic activity against C. albicans causing 4 log10 reduction of this fungus at 100 μM, which could be attributed to its high singlet oxygen yields, less aggregation in aqueous media, and relatively efficient cellular uptake.
Co-reporter:Zeli Yuan, Xiaomin Shen and Jiandong Huang
RSC Advances 2015 vol. 5(Issue 14) pp:10521-10528
Publication Date(Web):06 Jan 2015
DOI:10.1039/C4RA09168J
Three coordination polymers based on a tridentate N3-coordinated anthracene-containing tripodal ligand, 9-[(2,2′-dipicolylamino)methyl]anthracene (ADPA), namely [Cu(ADPA)Cl2]·H2O (1), [Ru(ADPA)Cl2DMSO]·4CH3OH·2H2O (2), and [Pt(ADPA)Cl]PF6·DMSO·2CH3OH·H2O (3), were synthesized and characterized using elemental analysis, 1H NMR, 13C NMR, FT-IR, and UV-vis spectroscopies, H RMS, and single-crystal XRD. X-ray structural analysis showed that the three compounds have mononuclear, 0D structures, which are further connected by hydrogen bonds into 3D supramolecular architectures. The antimicrobial activities of ADPA and compounds 1–3 were evaluated based on the minimum inhibitory concentration and minimum bactericidal concentration. The results showed that compounds 1–3 exhibit significant activities against Gram-positive bacteria (Staphylococcus aureus), and the Ru(II) and Pt(II) compounds have moderate antifungal activities (Candida albicans).
Co-reporter:Xing-Shu Li;Dr. Mei-Rong Ke;Wei Huang;Chun-Hong Ye ;Dr. Jian-Dong Huang
Chemistry - A European Journal 2015 Volume 21( Issue 8) pp:3310-3317
Publication Date(Web):
DOI:10.1002/chem.201404514
Abstract
A pH-responsive nanohybrid (LDH–ZnPcPS4), in which a highly hydrophilic zinc(II) phthalocyanine tetra-α-substituted with 4-sulfonatophenoxy groups (ZnPcPS4) is incorporated with a cationic layered double hydroxide (LDH) based on electrostatic interaction, has been specially designed and prepared through a facile co-precipitation approach. ZnPcPS4 is an excellent singlet-oxygen generator with strong absorption at the near-infrared region (692 nm) in cellular culture media, whereas the photoactivities of ZnPcPS4 were remarkably inhibited after incorporation with the LDH. The nanohybrid is essentially stable in aqueous media at pH 7.4; nevertheless, in slightly acidic media of pH 6.5 or 5.0, ZnPcPS4 can be efficiently released from the LDH matrix, thus leading to restoration of the photoactivities. The nanohybrid shows a high photocytotoxicity against HepG2 cells as a result of much more efficient cellular uptake and preferential accumulation in lysosomes, whereby the acidic environment leads to the release of ZnPcPS4. The IC50 value of LDH–ZnPcPS4 is as low as 0.053 μM, which is 24-fold lower than that of ZnPcPS4. This work provides a facile approach for the fabrication of photosensitizers with high photocytotoxicity, potential tumor selectivity, and rapid clearance character.
Co-reporter:Yanfang Geng, Jing Xu, Jindong Xue, Xiaomin Shen, Min Li, Jiandong Huang, Xiaokang Li, and Qingdao Zeng
Langmuir 2015 Volume 31(Issue 49) pp:13394-13401
Publication Date(Web):November 24, 2015
DOI:10.1021/acs.langmuir.5b03690
Molecular conformation is an important issue related to the self-assembly architecture and property. The self-assembly of silicon(IV) phthalocyanines covalently linked to the 5-N-cytidine or 4-carboxyphenoxy moiety at the axial positions, namely, SiPc(NC)2 and SiPc(CP)2, respectively, has been studied by means of scanning tunneling microscopy (STM) at the solid–liquid interface. The intermolecular axial hydrogen bonding in combination with the stabilizing role of the TCDB template brings about supramolecular self-assembled structures of silicon(IV) phthalocyanines in an edge-on orientation. Two pyridine compounds, 4,4′-bipyridine (BPY) and 1,2-di(4-pyridyl)ethylene (DPE), can tune the supramolecular structure, leading to interestingly axial self-assemblies of SiPc(CP)2 with BPY and DPE in an edge-on manner by hydrogen bonding. The results indicate that the axial substituents and the axial ligands can regulate and precisely control the conformation and arrangement of the phthalocyanine moiety on the graphite surface.
Co-reporter:Xiao-Min Shen, Bi-Yuan Zheng, Xiu-Rong Huang, Lei Wang and Jian-Dong Huang
Dalton Transactions 2013 vol. 42(Issue 29) pp:10398-10403
Publication Date(Web):30 May 2013
DOI:10.1039/C3DT50910A
A series of novel silicon(IV) phthalocyanines conjugated axially with different nucleoside moieties (uridine, 5-methyluridine, cytidine, and 5-N-cytidine derivatives) have been synthesized and evaluated for their photodynamic activities. The uridine-containing compound 1 exhibits the highest photocytotoxicity against HepG2 human hepatocarcinoma cells with an IC50 value as low as 6 nM, which can be attributed to its high cellular uptake and non-aggregated nature in the biological media. This compound shows high affinity toward the mitochondria of HepG2 cells and causes cell death mainly through apoptosis upon illumination. The result indicates that 1 is a highly promising photosensitizer for photodynamic therapy.
Co-reporter:Bi-Yuan Zheng, Hong-Peng Zhang, Mei-Rong Ke, Jian-Dong Huang
Dyes and Pigments 2013 Volume 99(Issue 1) pp:185-191
Publication Date(Web):October 2013
DOI:10.1016/j.dyepig.2013.04.032
•Photodynamic inactivation of C. albicans by a series of zinc(II) phthalocyanines was studied.•The structure-activity relationship of these phthalocyanines has been discussed.•The N-protecting of piperazinyl moiety affects significantly their photodynamic activities.•The mono-substituted phthalocyanine shows the highest photocytotoxicity against C. albicans.A series of novel zinc(II) phthalocyanines tetra-substituted or mono-substituted with piperazinyl moieties linked by different ethoxy chains has been prepared and characterized. The effects of the N-protecting group of piperazinyl moiety, length of ethoxy chains and number of substitutes on the photophysical, photochemical properties, cellular uptakes and in vitro photodynamic antifungal activities have also been examined. All of these compounds are essentially non-aggregated and good singlet oxygen generators with quantum yields (ΦΔ) of 0.54–0.77 in N,N-dimethylformamide. The photodynamic activity of these compounds against Candida albicans follows the order: 7 > 5a > 5b > 4a ≈ 4b. The mono-substituted phthalocyanine 7 exhibits the highest photodynamic inactivation of C. albicans with an IC90 value of 9 μM, which can be attributed to its better amphiphilicity and even higher cellular uptake. The results suggest that phthalocyanine 7 is a potential photosensitizer for antifungal photodynamic therapy.
Co-reporter:Bi-Yuan Zheng, Tao Lin, Huang-Hao Yang, Jian-Dong Huang
Dyes and Pigments 2013 Volume 96(Issue 2) pp:547-553
Publication Date(Web):February 2013
DOI:10.1016/j.dyepig.2012.09.013
The photodynamic activities against Candida albicans have been evaluated for seven silicon (IV) phthalocyanines modified axially by different functional groups. The effects of the axial substituents on the spectroscopic, photochemical, cellular uptake, and photobiological properties of these silicon phthlaocyanines have been revealed. The dicationic compounds 2 and 4, having two quaternary ammonium groups at the axial positions, exhibit the highest antifungal photocytotoxicity with an IC90 of 61–66 μM, which can be ascribed to their high singlet oxygen quantum yield, non-aggregation nature, effective cellular uptake, and intracellular distribution pattern (localizing preferentially in the mitochondria). By comparison, compounds 2 and 4 show a higher photodynamic inactivation of C. albicans cells than methylene blue (MB), a known antifungal photosensitizer. The IC90 values against C. albicans for 2 and 4 are ca. 8 times lower than that for MB. These results indicate that the dicationic silicon phthalocyanines 2 and 4 are interesting candidates as antifungal photosensitizers for future studies.Graphical abstractHighlights► Photodynamic inactivation of Candida albicans by a series of SiPcs was studied. ► The structure–activity relationship of these silicon phthalocyanines was discussed. ► The dicationic SiPcs 2 and 4 exhibit the highest antifungal photocytotoxicity. ► 2 and 4 show ca. 8 times higher photoactivities than methylene blue.
Co-reporter:Xing-Wei Chen;Dr. Mei-Rong Ke;Xing-Shu Li;Wen-Liang Lan;Miao-Fen Zhang ; Jian-Dong Huang
Chemistry – An Asian Journal 2013 Volume 8( Issue 12) pp:3063-3070
Publication Date(Web):
DOI:10.1002/asia.201300594
Abstract
Two new tetra- or di-α-substituted zinc(II) phthalocyanines 5 and 6 have been prepared through a “side-strapped” method. In the molecules, the adjacent benzene rings of the phthalocyanine core are linked at α-position through a triethylene glycol bridge to form a hybrid aza-/oxa-crown ether. The tetra-α-substituted phthalocyanine 5 shows an eclipsed self-assembly property in CH2Cl2 and the effect on the di-α-substituted analogue 6 is significantly weakened. Furthermore, the crown ethers of these compounds can selectively complex with Fe3+ or Cu2+ ion in DMF, leading to formation of J-aggregated nano-assemblies, which can be disaggregated in the presence of some organic or inorganic ligands, such as triethylamine, tetramethylethylenediamine, CH3COO−, or OH−. In addition, both compounds are efficient singlet oxygen generators with the singlet oxygen quantum yields (ΦΔ) of 0.54-0.74 in DMF relative to unsubstituted zinc(II) phthalocyanine (ΦΔ=0.56). They exhibit photodynamic activities toward HepG2 human hepatocarcinoma cells, but the compound 6, which has more than 40-fold lower IC50 value (0.08 μM) compared to the analogue 5 (IC50=3.31 μM), shows remarkablely higher in vitro photocytotoxicity due to its significantly higher cellular uptake and singlet oxygen generation efficiency. The results suggest that these compounds can serve as promising multifunctional materials both in (opto)electronic field and photodynamic therapy.
Co-reporter:Xiao-Min Shen, Xiong-Jie Jiang, Chang-Chang Huang, Han-Hui Zhang, Jian-Dong Huang
Tetrahedron 2010 66(46) pp: 9041-9048
Publication Date(Web):
DOI:10.1016/j.tet.2010.09.007
Co-reporter:Mei-Rong Ke, Jian-Dong Huang, Sheng-Mei Weng
Journal of Photochemistry and Photobiology A: Chemistry 2009 Volume 201(Issue 1) pp:23-31
Publication Date(Web):1 January 2009
DOI:10.1016/j.jphotochem.2008.09.011
A series of zinc phthalocyanines tetra-α-substituted with 4-(butoxycarbonyl) phenoxy groups (1a) or 4-carboxylphenoxy groups (2a) or 4-(2-carboxyl-ethyl)phenoxy groups (3a), and the corresponding tetra-β-substituted (1–3b) analogues, have been synthesized and characterized. The effects of the position of substituents at the phthalocyanine skeleton on their spectroscopic, photochemical and photobiological properties have been revealed. When compared with the tetra-β-substituted phthalocyanines, the corresponding tetra-α-substituted analogues exhibit a less aggregating trend in the cellular growth medium, a slightly higher singlet oxygen quantum yield and higher photo-stability in DMF, and a comparable cellular uptake. As a result, the tetra-α-substituted zinc phthalocyanines exhibit a higher photocytotoxicity toward MGC803 human gastric carcinoma cells than the tetra-β-substituted counterparts. Among all these compounds, phthalocyanine 2a shows the highest photodynamic activity, which may mainly be due to its non-aggregated nature in cellular culture medium and high cellular uptake.
Co-reporter:Xiong-Jie Jiang, Jian-Dong Huang, Yu-Jiao Zhu, Fen-Xiang Tang, Dennis K.P. Ng, Jian-Cheng Sun
Bioorganic & Medicinal Chemistry Letters 2006 Volume 16(Issue 9) pp:2450-2453
Publication Date(Web):1 May 2006
DOI:10.1016/j.bmcl.2006.01.075
Two novel axially substituted phthalocyanines, namely bis(4-(4-acetylpiperazine)phenoxy)phthalocyaninatosilicon (IV) (1) and its N-methylated derivative 2, have been synthesized. The dicationic phthalocyanine 2 is non-aggregated in water and exhibits good photophysical properties. The non-covalent BSA conjugates of these compounds have also been prepared. Compound 2 and the conjugate 2-BSA show extremely high photodynamic activities toward B16 melanoma cancer cell lines. The corresponding 50% growth-inhibitory (IC50) ratios are 33 and 38 nM, respectively.The new silicon (IV) phthalocyanine 2 was found to be essentially non-aggregated and strongly fluorescent in water. The compound and its non-covalent bovine serum albumin conjugate (2-BSA) exhibited extremely high photodynamic activities toward B16 melanoma cancer cell line with IC50 values down to 33 and 38 nM, respectively.
Co-reporter:Qun Sun, Bi-Yuan Zheng, Yan-Hong Zhang, Jing-Jing Zhuang, Mei-Rong Ke, Jian-Dong Huang
Dyes and Pigments (June 2017) Volume 141() pp:
Publication Date(Web):June 2017
DOI:10.1016/j.dyepig.2017.03.004
•Three SiPcs were modified with tyrosine derivatives through ester or ether bond.•The photophysical and biological properties are affected by the connection mode.•The SiPc 2 shows extremely high photocytotoxicity with an IC50 value of 1.3 nM.•Cremophor EL takes different effects on photocytotoxicity of these compounds.Three novel silicon(IV) phthalocyanines (SiPcs) axially substituted with l-tyrosine moieties possessing different modes of connection have been synthesized and characterized. The ester-linked SiPc 3 shows a slight red-shift of Q band, higher fluorescence emission and photosensitizing efficiency relative to the ether-linked SiPcs 1 and 2. However, SiPcs 1 and 2 exhibit more potent photocytotoxicity than SiPc 3, due to higher cellular uptake. When formulated with Cremophor EL™, all SiPcs show very high photocytotoxicity toward HepG2 cells, particularly for SiPc 2 which has a low IC50 value (1.3 nM). In the case of the phosphate buffered saline formulation, the photodynamic activities follow the trend 1 > 2 >> 3, which is different with that formulated with Cremophor EL™ (2 > 1 > 3). Thus, varying the mode of attachment of l-tyrosine moieties on the axial positions of SiPcs affects their photophysical and photochemical properties, and biological behavior.
Co-reporter:Haijun Chen, Xiaobin Zhou, Yu Gao, Biyuan Zheng, ... Jiandong Huang
Drug Discovery Today (April 2014) Volume 19(Issue 4) pp:502-509
Publication Date(Web):1 April 2014
DOI:10.1016/j.drudis.2014.01.010
•Photodynamic therapy (PDT) suffers from the major shortcoming derived from the limited penetrability of visible light.•Sonodynamic therapy (SDT) is deemed to overcome the disadvantage of PDT.•The concise update on recent advances in the development of new sonosensitizers for SDT is provided.•The future directions on the development of novel sonosensitizers are discussed.Developing an effective treatment for cancer is still a challenge. Despite great success with traditional cancer therapies, there are numerous disadvantages for conventional treatments such as systemic toxicity, low selectivity, drug resistance and potential long-term side effects. Recently, photodynamic therapy (PDT) has been widely applied in clinical settings. However, this approach suffers from the major shortcoming derived from the limited penetrability of visible light. Sonodynamic therapy (SDT) utilizing ultrasound combined with a sonosensitizer represents a novel noninvasive approach for cancer therapy, which is deemed to overcome the disadvantage of PDT. In this review, we extensively summarize the recent progress in the discovery of new sonosensitizers for SDT and discuss the future directions for the development of novel sonosensitizers.
Co-reporter:Xiao-Min Shen, Bi-Yuan Zheng, Xiu-Rong Huang, Lei Wang and Jian-Dong Huang
Dalton Transactions 2013 - vol. 42(Issue 29) pp:NaN10403-10403
Publication Date(Web):2013/05/30
DOI:10.1039/C3DT50910A
A series of novel silicon(IV) phthalocyanines conjugated axially with different nucleoside moieties (uridine, 5-methyluridine, cytidine, and 5-N-cytidine derivatives) have been synthesized and evaluated for their photodynamic activities. The uridine-containing compound 1 exhibits the highest photocytotoxicity against HepG2 human hepatocarcinoma cells with an IC50 value as low as 6 nM, which can be attributed to its high cellular uptake and non-aggregated nature in the biological media. This compound shows high affinity toward the mitochondria of HepG2 cells and causes cell death mainly through apoptosis upon illumination. The result indicates that 1 is a highly promising photosensitizer for photodynamic therapy.
Co-reporter:Xing-Shu Li, Mei-Rong Ke, Miao-Fen Zhang, Qing-Qing Tang, Bi-Yuan Zheng and Jian-Dong Huang
Chemical Communications 2015 - vol. 51(Issue 22) pp:NaN4707-4707
Publication Date(Web):2015/02/11
DOI:10.1039/C4CC09934F
A novel zinc(II) phthalocyanine bearing octa-sulphonates has been prepared, which is non-aggregated in water, highly photoactive and low dark-toxic. More interestingly, it exhibits specific affinity to macrophages via the scavenger receptor-A, and can selectively accumulate in tumour sites.
Co-reporter:Hai-Jun Chen, Xiu-Rong Huang, Xiao-Bin Zhou, Bi-Yuan Zheng and Jian-Dong Huang
Chemical Communications 2015 - vol. 51(Issue 22) pp:NaN4684-4684
Publication Date(Web):2015/02/06
DOI:10.1039/C5CC00927H
The potential application of artemether as a novel sonosensitizer for sonodynamic therapy (SDT) was explored and illustrated for the first time. In addition, liposome-encapsulated artemether exhibited significantly enhanced sonodynamic anticancer activity. Our findings indicated that artemisinin derivatives may serve as a new kind of sonosensitizer for SDT.
Co-reporter:Dong-Hua Wan, Bi-Yuan Zheng, Mei-Rong Ke, Ji-Ying Duan, Yun-Quan Zheng, Chih-Kuang Yeh and Jian-Dong Huang
Chemical Communications 2017 - vol. 53(Issue 29) pp:NaN4115-4115
Publication Date(Web):2017/03/20
DOI:10.1039/C6CC09541K
C-Phycocyanin (CPC) as a tumour-associated macrophage (TAM)-targeted photosensitiser has been first proved, and used as a vehicle of zinc phthalocyanine (ZnPc) to fabricate a ZnPc–CPC conjugate, which exhibits an efficient in vitro photodynamic activity, and selectively accumulates in tumour sites probably due to the affinity to TAM.
![Phenol, 2-[[(1H-indol-3-ylmethyl)(2-pyridinylmethyl)amino]methyl]-](http://img.cochemist.com/ccimg/481100/481050-72-0.png)
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![Phenol, 2-[[(2-pyridinylmethyl)amino]methyl]-](http://img.cochemist.com/ccimg/63700/63671-68-1.png)
![Phenol, 2-[[(2-pyridinylmethyl)amino]methyl]-](http://img.cochemist.com/ccimg/63700/63671-68-1_b.png)
