Targeted photodynamic therapy(TPDT)based on the photosensitizers responsive for tumor micr oenvironment is promising because of the better anti-tumor effect and less phototoxicity against normal tissue than the tradit...Targeted photodynamic therapy(TPDT)based on the photosensitizers responsive for tumor micr oenvironment is promising because of the better anti-tumor effect and less phototoxicity against normal tissue than the traditional PDT.Nanoparticle based stimuli responsive photo-sensitizers have been widely explored for TPDT.Based on the acidic microenvironments in solid tumors,an ultrasmall pH-responsive silicon phthalocyanine nanomicelle(PSN)(smaller than 10 nm)was designed for selective PDT of tumor.PSN had high drug loading efficacy(more than 28%)and exhibited morphological transitions,enhanced fuorescence and improved singlet∞x-ygen yield under acidic environments.PSN was renal dlearable and could rapidly accumulate and be retained at tumor sites,achieving a tumor-inhibiting ffect better than phthalocyanine micelle without pH response.Tumors of mice treated with PSN for PDT were completely ablated without recurrence.Thus,we have developed a phthalocyanine-based pH responsive micelle with excellent tumor targeting ability,which is expected to realize the selective PDT of tumor.展开更多
Silicon phthalocyanine derivatives 1a and 1b were synthesized and characterized by UV, <sup>1</sup>H-NMR and MS. The photophysical properties of the compounds in DMSO were investigated. The maximum absorpt...Silicon phthalocyanine derivatives 1a and 1b were synthesized and characterized by UV, <sup>1</sup>H-NMR and MS. The photophysical properties of the compounds in DMSO were investigated. The maximum absorption peaks of compounds 1a and 1b at the Q-band are 681 nm. With ZnPc (Φ<sub>F</sub> = 0.20, Φ<sub>Δ</sub> = 0.67) as a reference, the fluorescence quantum yield (Φ<sub>F</sub>) of 1a and 1b are 0.20 and 0.31 respectively, and the singlet oxygen quantum yield (Φ<sub>Δ</sub>) are 0.66 and 0.59 respectively. The DNA-photocleavage activities of compounds 1a and 1b were studied by gel electrophoresis. Compounds 1a and 1b possess good photocleavage activity to pBR322 DNA. The results demonstrate that compounds 1a and 1b are potential photosensitizers for tumor therapy.展开更多
Background: Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer photo...Background: Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer phototherapeutics. We evaluated the effectiveness of photodynamic therapy using Pc 4 in vitro and in vivo against human cervical cancer cells. Methods: CaSki and ME-180 cancer cells were grown as monolayers and spheroids. Cell growth and cytotoxicity were measured using a methylthiazol tetrazolium assay. Pc 4 cellular uptake and intracellular distribution were determined. For in vitro Pc 4 photodynamic therapy, cells were irradiated at 667 nm at a fluence of 2.5 J/cm<sup>2</sup> at 48 h. SCID mice were implanted with CaSki and ME-180 cells both subcutaneously and intracervically. Forty-eight hours after Pc 4 photodynamic therapy was administered at 75 and 150 J/cm<sup>2</sup>. Results: The IC<sub>50</sub>s for Pc 4 and Pc 4 photodynamic therapy for CaSki and ME-180 cells as monolayers were, 7.6 μM and 0.016 μM and >10 μM and 0.026 μM;as spheroids, IC<sub>50</sub>s of Pc 4 photodynamic therapy were, 0.26 μM and 0.01 μM. Pc 4 was taken up within cells and widely distributed in tumors and tissues. Intracervical photodynamic therapy resulted in tumor death, however mice died due to gastrointestinal toxicity. Photodynamic therapy resulted in subcutaneous tumor death and growth delay. Conclusions: Pc 4 photodynamic therapy caused death within cervical cancer cells and xenografts, supporting development of Pc 4 photodynamic therapy for treatment of cervical cancer. Support: P30-CA47904, CTSI BaCCoR Pilot Program.展开更多
Highly stable monolayers of 2,9,16,23-tetracarboxyl phthalocyanine on 3-aminopropyl -triethoxysilane (ATS) modified silicon and quartz substrates were prepared by reaction of carboxyl and amine. The monolayers were ch...Highly stable monolayers of 2,9,16,23-tetracarboxyl phthalocyanine on 3-aminopropyl -triethoxysilane (ATS) modified silicon and quartz substrates were prepared by reaction of carboxyl and amine. The monolayers were characterized by UV-Vis spectra and AFM measurements. The results indicated that the ultra-thin films on silicon or quartz were smooth, and the ordered structures were observed in these films.展开更多
Photoimmunotherapy(PIT)combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers(PS)and is a promising new cancer therapy.We designed and synthesized,in a highly convergent man...Photoimmunotherapy(PIT)combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers(PS)and is a promising new cancer therapy.We designed and synthesized,in a highly convergent manner,the silicon phthalocyanine dye WB692-CB2,which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to cysteines.In the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen(PSMA).The resulting antibody dye conjugate revealed high affinity and specificity towards PSMA-expressing prostate cancer cells and induced cell death after irradiation with red light.Treated cells exhibited morphological characteristics associated with pyroptosis.Mechanistic studies revealed the generation of reactive oxygen species,triggering a cascade of intracellular events involving lipid peroxidation,caspase-1 activation,gasdermin D cleavage and membrane rupture followed by release of pro-inflammatory cellular contents.In first in vivo experiments,PIT with our antibody dye conjugate led to a significant reduction of tumor growth and enhanced overall survival in mice bearing subcutaneous prostate tumor xenografts.Our study highlights the future potential of the new phthalocyanine dye WB692-CB2 as PS for the fluorescence-based detection and PIT of cancer,including local prostate tumor lesions,and systemic activation of anti-tumor immune responses by the induction of pyroptosis.展开更多
Silicon-phthalocyanine (SiPc) is chemically bonded to 3-aminopropltriethoxysilane (NH2(CH2)3Si(OC2H5)3, KH550) by the nucleophilic substituted reaction between the active chlorine of silicon dichlorine phthalocyanine ...Silicon-phthalocyanine (SiPc) is chemically bonded to 3-aminopropltriethoxysilane (NH2(CH2)3Si(OC2H5)3, KH550) by the nucleophilic substituted reaction between the active chlorine of silicon dichlorine phthalocyanine (SiPcCI2) and amino-group of KH550. The reacted product is hybridized with 3-glycidoxypropltrimethoxysilane (CH2OCHCH2O(CH2)3Si(OCH3)3, KH560) with sol-gel processing to form sol-gel inorganic material with good physical-chemical and optical properties. Due to tethering SiPc to the network, the aggregation of SiPc is effectively prevented in sol-gel derived matrix, and the doping concentration of SiPc in the form of monomer in the matrix is greatly enhanced. The cross-linkage of SiPcCI2 and KH550 is estimated and confirmed with FT-IR spectra. The optical limiting effects (OLE) of the gel with different content of SiPc are investigated with a frequency double Q-switched Nd3+:YAG laser of 8 nsec. pulse.展开更多
Thin silicon phthalocyanine dichloride films on HOPG were prepared and the sample was heated in the vacuum with laser. The thickness of the thin sample on HOPG was checked by X-ray photoemission spectroscopy. The orie...Thin silicon phthalocyanine dichloride films on HOPG were prepared and the sample was heated in the vacuum with laser. The thickness of the thin sample on HOPG was checked by X-ray photoemission spectroscopy. The orientation of the molecules in respect to the substrate plane was investigated by measuring the silicon K-edge near edge X-ray absorption fine structure （NEXAFS）. In the NEXAFS spectra of the thin sample, two clear peaks which were assigned to Is → σ^＊Si-N and 1s→ σ^＊Si-Cl appeared around 1847.2 eV and 1843.1 eV respectively. The intensities of the resonance peaks showed strong polarization dependence. A quantitative analysis of the polarization dependence revealed that the Si-N bond tended to lie down while the Si-Cl bond was out of the molecular plane.展开更多
The change of frictional force was studied with the increase of scan rate on different Si surface by atomic force microscopy.The results showed that frictional force had different effect with the increasement of scan ...The change of frictional force was studied with the increase of scan rate on different Si surface by atomic force microscopy.The results showed that frictional force had different effect with the increasement of scan rate on different surface.To Si surface and hydroxylate silicon surface,it became bigger.It first decreased and then increased on aminopropylsilanixed(APS)silicon surface,taking on conic section relation.It declined on monolayer copper phthalocyaninetetrasulfonic,tetrasodium salt(CuTsPc)molecular deposition film.In the process of scan,frictional heat greatly affected friction and may even change the shape of the film so that plastic flow arouse.展开更多
基金supported by grants from projects of Interdisciplinary Research Foundation of HIT,the National Natural Science Foundation of China(No.82071980)the International Cooperation and Exchanges NSFC-PSF(No.31961143003)+1 种基金the State Key Program of National Natural Science of China(No.81930047)the National Project for Research and Development of Major Scientifc Instruments(No.81727803).
文摘Targeted photodynamic therapy(TPDT)based on the photosensitizers responsive for tumor micr oenvironment is promising because of the better anti-tumor effect and less phototoxicity against normal tissue than the traditional PDT.Nanoparticle based stimuli responsive photo-sensitizers have been widely explored for TPDT.Based on the acidic microenvironments in solid tumors,an ultrasmall pH-responsive silicon phthalocyanine nanomicelle(PSN)(smaller than 10 nm)was designed for selective PDT of tumor.PSN had high drug loading efficacy(more than 28%)and exhibited morphological transitions,enhanced fuorescence and improved singlet∞x-ygen yield under acidic environments.PSN was renal dlearable and could rapidly accumulate and be retained at tumor sites,achieving a tumor-inhibiting ffect better than phthalocyanine micelle without pH response.Tumors of mice treated with PSN for PDT were completely ablated without recurrence.Thus,we have developed a phthalocyanine-based pH responsive micelle with excellent tumor targeting ability,which is expected to realize the selective PDT of tumor.
文摘Silicon phthalocyanine derivatives 1a and 1b were synthesized and characterized by UV, <sup>1</sup>H-NMR and MS. The photophysical properties of the compounds in DMSO were investigated. The maximum absorption peaks of compounds 1a and 1b at the Q-band are 681 nm. With ZnPc (Φ<sub>F</sub> = 0.20, Φ<sub>Δ</sub> = 0.67) as a reference, the fluorescence quantum yield (Φ<sub>F</sub>) of 1a and 1b are 0.20 and 0.31 respectively, and the singlet oxygen quantum yield (Φ<sub>Δ</sub>) are 0.66 and 0.59 respectively. The DNA-photocleavage activities of compounds 1a and 1b were studied by gel electrophoresis. Compounds 1a and 1b possess good photocleavage activity to pBR322 DNA. The results demonstrate that compounds 1a and 1b are potential photosensitizers for tumor therapy.
文摘Background: Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer phototherapeutics. We evaluated the effectiveness of photodynamic therapy using Pc 4 in vitro and in vivo against human cervical cancer cells. Methods: CaSki and ME-180 cancer cells were grown as monolayers and spheroids. Cell growth and cytotoxicity were measured using a methylthiazol tetrazolium assay. Pc 4 cellular uptake and intracellular distribution were determined. For in vitro Pc 4 photodynamic therapy, cells were irradiated at 667 nm at a fluence of 2.5 J/cm<sup>2</sup> at 48 h. SCID mice were implanted with CaSki and ME-180 cells both subcutaneously and intracervically. Forty-eight hours after Pc 4 photodynamic therapy was administered at 75 and 150 J/cm<sup>2</sup>. Results: The IC<sub>50</sub>s for Pc 4 and Pc 4 photodynamic therapy for CaSki and ME-180 cells as monolayers were, 7.6 μM and 0.016 μM and >10 μM and 0.026 μM;as spheroids, IC<sub>50</sub>s of Pc 4 photodynamic therapy were, 0.26 μM and 0.01 μM. Pc 4 was taken up within cells and widely distributed in tumors and tissues. Intracervical photodynamic therapy resulted in tumor death, however mice died due to gastrointestinal toxicity. Photodynamic therapy resulted in subcutaneous tumor death and growth delay. Conclusions: Pc 4 photodynamic therapy caused death within cervical cancer cells and xenografts, supporting development of Pc 4 photodynamic therapy for treatment of cervical cancer. Support: P30-CA47904, CTSI BaCCoR Pilot Program.
文摘Highly stable monolayers of 2,9,16,23-tetracarboxyl phthalocyanine on 3-aminopropyl -triethoxysilane (ATS) modified silicon and quartz substrates were prepared by reaction of carboxyl and amine. The monolayers were characterized by UV-Vis spectra and AFM measurements. The results indicated that the ultra-thin films on silicon or quartz were smooth, and the ordered structures were observed in these films.
基金German Research Foundation(DFG,grant no.WO 2178/3–1 to PW)Federal Ministry of Economic Affairs and Climate Action(BMWK,grant no.03THW15H04 to RB and PW)supported by the Open Access Publication Fund of the University of Freiburg.
文摘Photoimmunotherapy(PIT)combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers(PS)and is a promising new cancer therapy.We designed and synthesized,in a highly convergent manner,the silicon phthalocyanine dye WB692-CB2,which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to cysteines.In the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen(PSMA).The resulting antibody dye conjugate revealed high affinity and specificity towards PSMA-expressing prostate cancer cells and induced cell death after irradiation with red light.Treated cells exhibited morphological characteristics associated with pyroptosis.Mechanistic studies revealed the generation of reactive oxygen species,triggering a cascade of intracellular events involving lipid peroxidation,caspase-1 activation,gasdermin D cleavage and membrane rupture followed by release of pro-inflammatory cellular contents.In first in vivo experiments,PIT with our antibody dye conjugate led to a significant reduction of tumor growth and enhanced overall survival in mice bearing subcutaneous prostate tumor xenografts.Our study highlights the future potential of the new phthalocyanine dye WB692-CB2 as PS for the fluorescence-based detection and PIT of cancer,including local prostate tumor lesions,and systemic activation of anti-tumor immune responses by the induction of pyroptosis.
文摘Silicon-phthalocyanine (SiPc) is chemically bonded to 3-aminopropltriethoxysilane (NH2(CH2)3Si(OC2H5)3, KH550) by the nucleophilic substituted reaction between the active chlorine of silicon dichlorine phthalocyanine (SiPcCI2) and amino-group of KH550. The reacted product is hybridized with 3-glycidoxypropltrimethoxysilane (CH2OCHCH2O(CH2)3Si(OCH3)3, KH560) with sol-gel processing to form sol-gel inorganic material with good physical-chemical and optical properties. Due to tethering SiPc to the network, the aggregation of SiPc is effectively prevented in sol-gel derived matrix, and the doping concentration of SiPc in the form of monomer in the matrix is greatly enhanced. The cross-linkage of SiPcCI2 and KH550 is estimated and confirmed with FT-IR spectra. The optical limiting effects (OLE) of the gel with different content of SiPc are investigated with a frequency double Q-switched Nd3+:YAG laser of 8 nsec. pulse.
基金Nuclear Researchers Exchange Program 2005Photon Factory Program Advisory Committee (2004G340)
文摘Thin silicon phthalocyanine dichloride films on HOPG were prepared and the sample was heated in the vacuum with laser. The thickness of the thin sample on HOPG was checked by X-ray photoemission spectroscopy. The orientation of the molecules in respect to the substrate plane was investigated by measuring the silicon K-edge near edge X-ray absorption fine structure （NEXAFS）. In the NEXAFS spectra of the thin sample, two clear peaks which were assigned to Is → σ^＊Si-N and 1s→ σ^＊Si-Cl appeared around 1847.2 eV and 1843.1 eV respectively. The intensities of the resonance peaks showed strong polarization dependence. A quantitative analysis of the polarization dependence revealed that the Si-N bond tended to lie down while the Si-Cl bond was out of the molecular plane.
文摘The change of frictional force was studied with the increase of scan rate on different Si surface by atomic force microscopy.The results showed that frictional force had different effect with the increasement of scan rate on different surface.To Si surface and hydroxylate silicon surface,it became bigger.It first decreased and then increased on aminopropylsilanixed(APS)silicon surface,taking on conic section relation.It declined on monolayer copper phthalocyaninetetrasulfonic,tetrasodium salt(CuTsPc)molecular deposition film.In the process of scan,frictional heat greatly affected friction and may even change the shape of the film so that plastic flow arouse.
