Focused on the performance promotion of organic small molecular dyes based photothermal agents via non-chemical modification,we found that heat-assisted binding of human serum albumin(HSA)to the dye causes shrinkage o...Focused on the performance promotion of organic small molecular dyes based photothermal agents via non-chemical modification,we found that heat-assisted binding of human serum albumin(HSA)to the dye causes shrinkage of the protein and encapsulate the dye to form nanoparticles.This revolutionizes the photostability of small molecule dyes which further improves their photothermal conversion effi-ciency and tumor ablation performance as photothermal agents significantly.In this work,the obtained photothermal agent named HSA-P2-T could accumulate in tumor and induce 22℃enhancement of the tumor in xenograft models upon ultra-low dose(0.1 W/cm^(2))laser irradiation,which,as far as we know,is the lowest laser dose used in vivo photothermal therapy.Utilizing HSA-P2-T,we realized tumor ablation upon twice intravenous injections of the nanoparticles and four photothermal treatments.展开更多
Photodynamic therapy(PDT) has shown promise as an effective treatment modality for cancer and other localized diseases due to its noninvasive properties and spatiotemporal selectivity. Near-infrared(NIR)fluorescent dy...Photodynamic therapy(PDT) has shown promise as an effective treatment modality for cancer and other localized diseases due to its noninvasive properties and spatiotemporal selectivity. Near-infrared(NIR)fluorescent dyes based on organic small molecules are characterized with low cytotoxicity, good biocompatibility and excellent phototoxicity, which are widely used in PDT. In this review, we attempt to summarize the development of imaging-induced PDT based on organic small molecules and classify it according to the structures of dyes including cyanines, 4,4-difluoro-4-bora-3 a,4 a-diaza-s-indacene(BODIPY) analogues, phthalocyanine and other agents such as rhodamine analogues.展开更多
Near-infrared(NIR)fluorescent dyes based on small organic molecules are characterized with low cytotoxicity,good biocompatibility and minimum interference from auto-fluorescence background,which are widely used in tum...Near-infrared(NIR)fluorescent dyes based on small organic molecules are characterized with low cytotoxicity,good biocompatibility and minimum interference from auto-fluorescence background,which are widely used in tumor diagnosis.Intensive research on molecular properties and photothermal properties of fluorescent dyes have been explored for non-invasive photothermal treatment of cancer.In this review,we focus on the development of imaging-induced photothermal therapy of small molecules and classification according to the structures of organic molecules including cyanines,phthalocyanines,rhodamine analogues and BODIPYs.展开更多
Photodynamic therapy with reactive oxygen species production is a prospective treatment to combat cancer stem cells(CSCs).However,the innate drawbacks,including short lifetime and diffusion distance of reactive oxygen...Photodynamic therapy with reactive oxygen species production is a prospective treatment to combat cancer stem cells(CSCs).However,the innate drawbacks,including short lifetime and diffusion distance of reactive oxygen species and hypoxia within solid tumors,have become bottlenecks for clinical applications of photodynamic therapy.Here,we develop a mitochondria-targeting hemicyanine-oleic acid conjugate(CyOA),which can self-assemble into supramolecular nanoparticles(NPs)without any exogenous excipients.CyOA is also shown for targeting the mitochondrial complex II protein succinate dehydrogenase to inhibit oxidative phosphorylation and reverse tumor hypoxia,resulting in 50.4-fold higher phototoxicity against breast cancer stem cells(BCSCs)compared to SO_(3)-CyOA NPs that cannot target to mitochondria.In 4T1 and BCSC tumor models,CyOA NPs achieve higher tumor inhibition and less lung metastasis nodules compared to the clinically used photosensitizer Hiporfin.This study develops a self-assembled small molecule that can serve as both oxidative phosphorylation inhibitor and photosensitizer for eradication of CSCs and treatment of solid tumors.展开更多
In the past decades,porphyrins,phthalocyanines and related materials have attracted significant attention due to their diverse and brilliant structures[1,2],as well as their unique electronic structures and photophysi...In the past decades,porphyrins,phthalocyanines and related materials have attracted significant attention due to their diverse and brilliant structures[1,2],as well as their unique electronic structures and photophysical properties which could be applicable in a wide range of areas[3–5].展开更多
J-aggregates of cyanine have shown great merits in tumor photothermal therapy(PTT)due to their distinct redshift absorption as well as superior photothermal conversion efficiency(PCE).However,due to the complexity of ...J-aggregates of cyanine have shown great merits in tumor photothermal therapy(PTT)due to their distinct redshift absorption as well as superior photothermal conversion efficiency(PCE).However,due to the complexity of intermolecular interactions,especially the impact of steric hindrance on aggregation,exploring effective strategies to regulate the aggregation modes of organic materials remains challenging.Herein,steric hindrance-regulated J-aggregation of near-infrared(NIR)cyanine was reported based on Pt-coordinated cyanine self-assembly with unexpected“butterfly effect”.Two Pt-coordinated cyanine dimers CyR-Pt(R=Me and Et)were synthesized and spontaneously self-assembled into aggregates in aqueous solution.CyEt-Pt aggregates were loose and amorphous stacking.By replacing ethyl with methyl to reduce steric hindrance,a tiny change resulted in the generation of tightly stacked cyanine J-aggregates(thickness less than 3 nm)observed in CyMe-Pt self-assembly.Significantly,this unexpected“butterfly effect”enabled CyMe-Pt J-aggregates to effectively inhibit reactive oxygen species and greatly improve its photostability.Besides,CyMe-Pt J-aggregates with NIR-II absorption exhibited outstanding photothermal stability and higher PCE(η=37%)than CyEt-Pt disordered aggregates(η=20%).Evident tumor suppression performance of CyMe-Pt J-aggregates was validated under 980 nm laser irradiation,demonstrating its great potential in tumor PTT.展开更多
The photothermal therapy(PTT) has come across as a promising noninvasive therapeutic strategy for tumor treatment. However, low photothermal conversion efficiency(PCE) and hydrophobicity may impede the therapeutic eff...The photothermal therapy(PTT) has come across as a promising noninvasive therapeutic strategy for tumor treatment. However, low photothermal conversion efficiency(PCE) and hydrophobicity may impede the therapeutic efficacy of organic photothermal agents and an efficient PTT-agent must overcome these two major challenges. In this work, we developed a new strategy to promote higher PCE wherein the intermolecular hydrogen-bonding interaction between the single dye molecule and water facilitated the transformation of the absorbed energy into the heat. A hydrophilic squaraine dye(SCy1) with the second near-infrared region(NIR-II) absorption and extremely low emission were designed to exhibit much higher PCE than that of the analogues of pentamethine-dyes(PCy1, PCy2). The presence of the ‘–O-' at middle of squaric cycle enabled the intermolecular H-bonding formation between the SCy1 and water to promote the energy dissipation channel. Moreover, the introduction of long-chain phenylsulfonate groups helped in to improve the water solubility apart from serving as an additional means of further enhancing PCE through fluorescence quenching. Therefore, SCy1 with a squaraine backbone and long-chain sulfonate moieties revealed outstanding photothermal stability and anti-aggregation activity apart from showing exceptionally high PCE(74%) in water. SCy1 demonstrated excellent therapeutic efficacy when applied in the PTT treatment of tumor-bearing mice under a laser irradiation of 915 nm.展开更多
Near infrared(NIR) absorbing and emitting dyes are sought after for their potentials in bioimaging and theranostic applications. They are typically not as stable as dyes absorbing and emitting in the visible spectral ...Near infrared(NIR) absorbing and emitting dyes are sought after for their potentials in bioimaging and theranostic applications. They are typically not as stable as dyes absorbing and emitting in the visible spectral range, as the result of a reduced HOMO-LUMO band-gap. Also, they are not as efficient fluorescence emitters due to accelerated internal conversion kinetics. In addition, their large conjugative backbone render them high tendency to form aggregate and low aqueous solubility. In this tutorial, we have described a four-step approach for rational design of organic dyes with an overall high-performance to meet the rigorous requirements of biological applications. Also, some background regarding "NIR" is provided along with some recent breakthroughs of the field.展开更多
Amino acids containing the thiol group play significant roles in keeping biological oxidation reduction balance. Due to the important cellular function of biothiols, it is imperative to develop efficient methods to de...Amino acids containing the thiol group play significant roles in keeping biological oxidation reduction balance. Due to the important cellular function of biothiols, it is imperative to develop efficient methods to detect biothiols in complicate biological systems. In this work, we developed a cyanine-based fluorescent probe utilizing thioether as a detecting group, which showed the fluorescent ＂turn-on＂ response towards GSH and it can be used as a biomarker to determine the cellular GSH.展开更多
Developing the novel fluorescent dyes with a larger Stokes shift is still a challenge in the research of fluorescence probes. In this work, a naphthalimide-modified near-infrared cyanine dye with an emission at 785 nm...Developing the novel fluorescent dyes with a larger Stokes shift is still a challenge in the research of fluorescence probes. In this work, a naphthalimide-modified near-infrared cyanine dye with an emission at 785 nm has been synthesized for lysosome-targeting imaging. This fluorescent dye showed a large Stokes shift（up to 165 nm） and favorable lysosome-targeting property, which facilitated it to be a potential candidate for studying of lysosomal functions. The result also indicated that the probe is a promising contrast agent for in vivo imaging in mouse models.展开更多
The intersystem crossing and isomerization dynamics of free-Cy3,Cy3-ssDNA,free-Cy5 and Cy5-ssDNA are obtained through simple analysis of rapid on/off blinking from single molecule fluorescence intensity time-traces an...The intersystem crossing and isomerization dynamics of free-Cy3,Cy3-ssDNA,free-Cy5 and Cy5-ssDNA are obtained through simple analysis of rapid on/off blinking from single molecule fluorescence intensity time-traces and the fluorescence correlation spectroscopy(FCS).The on-and off-times observed in fluorescence time traces of single cyanine dyes are due to the formation of the triplet state and isomerization,where both the interaction with DNA and long central polymethine chain of cyanine dyes increase the barriers of isomerization,leading to long off-time.The results indicate that the single molecule fluorescence fluctuation together with the resulting second autocorrelation analysis are powerful methods for determining the triplet state and isomerization dynamics,which could be the simple techniques and complementary to other spectroscopic techniques,such as fluorescence decay measurement and laser flash photolysis to study the photophysical processes of complex molecules.展开更多
基金the National Natural Science Foundation of China(Nos.22277069,22074084)Program of the State Key Laboratory of Quantum Optics and Optical Quantum Devices of Shanxi University(No.KF202108).
文摘Focused on the performance promotion of organic small molecular dyes based photothermal agents via non-chemical modification,we found that heat-assisted binding of human serum albumin(HSA)to the dye causes shrinkage of the protein and encapsulate the dye to form nanoparticles.This revolutionizes the photostability of small molecule dyes which further improves their photothermal conversion effi-ciency and tumor ablation performance as photothermal agents significantly.In this work,the obtained photothermal agent named HSA-P2-T could accumulate in tumor and induce 22℃enhancement of the tumor in xenograft models upon ultra-low dose(0.1 W/cm^(2))laser irradiation,which,as far as we know,is the lowest laser dose used in vivo photothermal therapy.Utilizing HSA-P2-T,we realized tumor ablation upon twice intravenous injections of the nanoparticles and four photothermal treatments.
基金the Natural Science Foundation Committee of China (NSFC,No.81671803)the National Key Research and Development Program (No.2017YFC0107700)+6 种基金the Outstanding Youth Foundation of Jiangsu Province (Nos.GX20171114003, BK20170030)Fok Ying Tung Education Foundation (No.161033)"Double First-Class" University Project (Nos.CPU2018GY06 and CPU2018GY24)the Priority Academic Program Development of Jiangsu Higher Education Institutions for their financial supportthe National Natural Science Foundation of China (Nos.21676113,21402057,21772054,21472059)Distinguished Young Scholar of Hubei Province (No.2018CFA079) for the financial supportsupported by the 111 Project (No.B17019)
文摘Photodynamic therapy(PDT) has shown promise as an effective treatment modality for cancer and other localized diseases due to its noninvasive properties and spatiotemporal selectivity. Near-infrared(NIR)fluorescent dyes based on organic small molecules are characterized with low cytotoxicity, good biocompatibility and excellent phototoxicity, which are widely used in PDT. In this review, we attempt to summarize the development of imaging-induced PDT based on organic small molecules and classify it according to the structures of dyes including cyanines, 4,4-difluoro-4-bora-3 a,4 a-diaza-s-indacene(BODIPY) analogues, phthalocyanine and other agents such as rhodamine analogues.
基金the Natural Science Foundation Committee of China(NSFC, No. 81671803)the National Key Research and Development Program(No. 2017YFC0107700)+6 种基金the Outstanding Youth Foundation of Jiangsu Province (Nos. GX20171114003, BK20170030)Fok Ying Tung Education Foundation(No. 161033)"Double First-Class" University project(Nos. CPU2018GY06 and CPU2018GY24)the Priority Academic Program Development of Jiangsu Higher Education Institutions, for their financial supportthe National Natural Science Foundation of China(Nos. 21676113,21402057, 21772054, 21472059)Distinguished Young Scholar of Hubei Province(No. 2018CFA079)for the financial supportsupported by the 111 Project (No. B17019)
文摘Near-infrared(NIR)fluorescent dyes based on small organic molecules are characterized with low cytotoxicity,good biocompatibility and minimum interference from auto-fluorescence background,which are widely used in tumor diagnosis.Intensive research on molecular properties and photothermal properties of fluorescent dyes have been explored for non-invasive photothermal treatment of cancer.In this review,we focus on the development of imaging-induced photothermal therapy of small molecules and classification according to the structures of organic molecules including cyanines,phthalocyanines,rhodamine analogues and BODIPYs.
基金supported by the National Research and Development Program of China(2018YFA0208900,2020YFA0710700,and 2020YFA0211200)the National Science Foundation of China(82172757 and 31972927)+2 种基金the Program for HUST Academic Frontier Youth Team(2018QYTD01)the Scientific Research Foundation of HUST(3004170130)the HCP Program for HUST.
文摘Photodynamic therapy with reactive oxygen species production is a prospective treatment to combat cancer stem cells(CSCs).However,the innate drawbacks,including short lifetime and diffusion distance of reactive oxygen species and hypoxia within solid tumors,have become bottlenecks for clinical applications of photodynamic therapy.Here,we develop a mitochondria-targeting hemicyanine-oleic acid conjugate(CyOA),which can self-assemble into supramolecular nanoparticles(NPs)without any exogenous excipients.CyOA is also shown for targeting the mitochondrial complex II protein succinate dehydrogenase to inhibit oxidative phosphorylation and reverse tumor hypoxia,resulting in 50.4-fold higher phototoxicity against breast cancer stem cells(BCSCs)compared to SO_(3)-CyOA NPs that cannot target to mitochondria.In 4T1 and BCSC tumor models,CyOA NPs achieve higher tumor inhibition and less lung metastasis nodules compared to the clinically used photosensitizer Hiporfin.This study develops a self-assembled small molecule that can serve as both oxidative phosphorylation inhibitor and photosensitizer for eradication of CSCs and treatment of solid tumors.
文摘In the past decades,porphyrins,phthalocyanines and related materials have attracted significant attention due to their diverse and brilliant structures[1,2],as well as their unique electronic structures and photophysical properties which could be applicable in a wide range of areas[3–5].
基金supported financially by Guangdong Basic and Applied Basic Research Foundation(2019A1515110441)the Natural Science Foundation of Shandong Province(ZR2020QB001)+1 种基金the National Key Research and Development Program of China(2023YFC3403000)the National Natural Science Foundation of China(22378231 and 22001148)。
文摘J-aggregates of cyanine have shown great merits in tumor photothermal therapy(PTT)due to their distinct redshift absorption as well as superior photothermal conversion efficiency(PCE).However,due to the complexity of intermolecular interactions,especially the impact of steric hindrance on aggregation,exploring effective strategies to regulate the aggregation modes of organic materials remains challenging.Herein,steric hindrance-regulated J-aggregation of near-infrared(NIR)cyanine was reported based on Pt-coordinated cyanine self-assembly with unexpected“butterfly effect”.Two Pt-coordinated cyanine dimers CyR-Pt(R=Me and Et)were synthesized and spontaneously self-assembled into aggregates in aqueous solution.CyEt-Pt aggregates were loose and amorphous stacking.By replacing ethyl with methyl to reduce steric hindrance,a tiny change resulted in the generation of tightly stacked cyanine J-aggregates(thickness less than 3 nm)observed in CyMe-Pt self-assembly.Significantly,this unexpected“butterfly effect”enabled CyMe-Pt J-aggregates to effectively inhibit reactive oxygen species and greatly improve its photostability.Besides,CyMe-Pt J-aggregates with NIR-II absorption exhibited outstanding photothermal stability and higher PCE(η=37%)than CyEt-Pt disordered aggregates(η=20%).Evident tumor suppression performance of CyMe-Pt J-aggregates was validated under 980 nm laser irradiation,demonstrating its great potential in tumor PTT.
基金financially supported by the National Natural Science Foundation of China (No.61875131)Shenzhen Key Laboratory of Photonics and Biophotonics (No.ZDSYS20210623092006020)。
文摘The photothermal therapy(PTT) has come across as a promising noninvasive therapeutic strategy for tumor treatment. However, low photothermal conversion efficiency(PCE) and hydrophobicity may impede the therapeutic efficacy of organic photothermal agents and an efficient PTT-agent must overcome these two major challenges. In this work, we developed a new strategy to promote higher PCE wherein the intermolecular hydrogen-bonding interaction between the single dye molecule and water facilitated the transformation of the absorbed energy into the heat. A hydrophilic squaraine dye(SCy1) with the second near-infrared region(NIR-II) absorption and extremely low emission were designed to exhibit much higher PCE than that of the analogues of pentamethine-dyes(PCy1, PCy2). The presence of the ‘–O-' at middle of squaric cycle enabled the intermolecular H-bonding formation between the SCy1 and water to promote the energy dissipation channel. Moreover, the introduction of long-chain phenylsulfonate groups helped in to improve the water solubility apart from serving as an additional means of further enhancing PCE through fluorescence quenching. Therefore, SCy1 with a squaraine backbone and long-chain sulfonate moieties revealed outstanding photothermal stability and anti-aggregation activity apart from showing exceptionally high PCE(74%) in water. SCy1 demonstrated excellent therapeutic efficacy when applied in the PTT treatment of tumor-bearing mice under a laser irradiation of 915 nm.
基金supported by the National Natural Science Foundation of China (Nos. 21574039 and 21822805)Shanghai Municipal Science and Technology Commission (No. 18DZ1112703)
文摘Near infrared(NIR) absorbing and emitting dyes are sought after for their potentials in bioimaging and theranostic applications. They are typically not as stable as dyes absorbing and emitting in the visible spectral range, as the result of a reduced HOMO-LUMO band-gap. Also, they are not as efficient fluorescence emitters due to accelerated internal conversion kinetics. In addition, their large conjugative backbone render them high tendency to form aggregate and low aqueous solubility. In this tutorial, we have described a four-step approach for rational design of organic dyes with an overall high-performance to meet the rigorous requirements of biological applications. Also, some background regarding "NIR" is provided along with some recent breakthroughs of the field.
文摘Amino acids containing the thiol group play significant roles in keeping biological oxidation reduction balance. Due to the important cellular function of biothiols, it is imperative to develop efficient methods to detect biothiols in complicate biological systems. In this work, we developed a cyanine-based fluorescent probe utilizing thioether as a detecting group, which showed the fluorescent ＂turn-on＂ response towards GSH and it can be used as a biomarker to determine the cellular GSH.
基金support from National Natural Science Foundation of China (Nos. 21676113, 21402057, 21472059, 81671803)Youth Chen-Guang Project of Wuhan (2016070204010098)+2 种基金the 111 Project B17019the Ministry Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhensupported by Self-determined Research Funds of CCNU from the colleges’ basic research and operation of MOE (No. CCNU16A02004)
文摘Developing the novel fluorescent dyes with a larger Stokes shift is still a challenge in the research of fluorescence probes. In this work, a naphthalimide-modified near-infrared cyanine dye with an emission at 785 nm has been synthesized for lysosome-targeting imaging. This fluorescent dye showed a large Stokes shift（up to 165 nm） and favorable lysosome-targeting property, which facilitated it to be a potential candidate for studying of lysosomal functions. The result also indicated that the probe is a promising contrast agent for in vivo imaging in mouse models.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 20773139, 20833008 & 20825314)State Key Project for Fundamental Research (Grant Nos. 2006CB806000 & 2007CB815200)
文摘The intersystem crossing and isomerization dynamics of free-Cy3,Cy3-ssDNA,free-Cy5 and Cy5-ssDNA are obtained through simple analysis of rapid on/off blinking from single molecule fluorescence intensity time-traces and the fluorescence correlation spectroscopy(FCS).The on-and off-times observed in fluorescence time traces of single cyanine dyes are due to the formation of the triplet state and isomerization,where both the interaction with DNA and long central polymethine chain of cyanine dyes increase the barriers of isomerization,leading to long off-time.The results indicate that the single molecule fluorescence fluctuation together with the resulting second autocorrelation analysis are powerful methods for determining the triplet state and isomerization dynamics,which could be the simple techniques and complementary to other spectroscopic techniques,such as fluorescence decay measurement and laser flash photolysis to study the photophysical processes of complex molecules.
