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
To improve the selective separation performance of silica nanofibers(SiO_(2)NFs)for cesium ions(Cs+)and overcome the defects of Prussian blue nanoparticles(PB NPs),PB/SiO_(2)-NH_(2)NFs were prepared to remove Cs^(+)fr...To improve the selective separation performance of silica nanofibers(SiO_(2)NFs)for cesium ions(Cs+)and overcome the defects of Prussian blue nanoparticles(PB NPs),PB/SiO_(2)-NH_(2)NFs were prepared to remove Cs^(+)from water.Among them,3-aminopropyltriethoxysilane(APTES)underwent an alkylation reaction with SiO_(2),resulting in the formation of a dense Si-O-Si network structure that decorated the surface of SiO_(2)NFs.Meanwhile,the amino functional groups in APTES combined with Fe3+and then reacted with Fe2+to form PB NPs,which anchored firmly on the aminoated SiO_(2)NFs surface.In our experiment,the maxi-mumadsorption capacity of PB/SiO_(2)-NH_(2)NFs was 111.38 mg/g,which was 31.5mg/g higher than that of SiO_(2)NFs.At the same time,after the fifth cycle,the removal rate of Cs^(+)by PB/SiO_(2)-NH_(2)NFs adsorbent was 75.36%±3.69%.In addition,the adsorption isotherms and adsorption kinetics of PB/SiO_(2)-NH_(2)NFs were combined with the Freundlich model and the quasi-two-stage fitting model,respectively.Further mechanism analysis showed that the bond between PB/SiO_(2)-NH_(2)NFs and Cs^(+)was mainly a synergistic action of ion exchange,electrostatic adsorption and membrane separation.展开更多
By adsorbing chitosan(CS)-functionalized Prussian blue(PB) nanoparticles(CS/PB NPs) complexing DNA onto the surface of gas encapsulated microbubbles(MBs), a multifunctional gene delivery system of MBs@CS/PB/DNA was fa...By adsorbing chitosan(CS)-functionalized Prussian blue(PB) nanoparticles(CS/PB NPs) complexing DNA onto the surface of gas encapsulated microbubbles(MBs), a multifunctional gene delivery system of MBs@CS/PB/DNA was fabricated for photothermally enhanced gene transfection through ultrasound-targeted microbubble destruction. CS/PB NPs of(2.69 ± 0.49) nm could complex DNA effectively when the mass ratio was2:1. It was found that MBs@CS/PB/DNA could enhance ultrasound imaging greatly both in vitro and in vivo. In addition, MBs@CS/PB/DNA could be disrupted by applying a higher-intensity ultrasound irradiation to release CS/PB/DNA, which could effectively transform the nearinfrared(NIR) light into heat to assist the uptake of CS/PB/DNA by cells. With the aid of ultrasound irradiation and NIR light irradiation, the gene transfection efficiency was significantly enhanced to(43.08 ± 1.13) %, much higher than polyethylenimine. Moreover, MBs@CS/PB/DNA showed excellent biocompatibility, encouraging the further exploration of MBs@CS/PB/DNA to be a platform for combined ultrasound image, photothermal therapy, drug delivery, and gene therapy.展开更多
Stage IV breast cancer,which has a high risk of invasion,often develops into metastases in distant organs,especially in the lung,and this could threaten the lives of women.Thus,the development of more advanced therape...Stage IV breast cancer,which has a high risk of invasion,often develops into metastases in distant organs,especially in the lung,and this could threaten the lives of women.Thus,the development of more advanced therapeutics that can efficiently target metastatic foci is crucial.In this study,we built an dual-acting therapeutic strategy using micelles with high stability functionalized with fibronectin-targeting CREKA peptides encapsulating two slightly soluble chemotherapy agents in water,doxorubicin(D)and vinorelbine(V),which we termed C-DVM.We found that small C-DVM micelles could efficiently codeliver drugs into 4T1 cells and disrupt microtubule structures.C-DVM also exhibited a powerful ability to eradicate and inhibit invasion of 4T1 cells.Moreover,an in vivo pharmacokinetics study showed that C-DVM increased the drug circulation half-life and led to increased enrichment of drugs in lung metastatic foci after 24 h.Moreover,dual-acting C-DVM treatment led to 90%inhibition of metastatic foci development and reduced invasion of metastases.C-DVM could potentially be used as a targeted treatment for metastasis and represents a new approach with higher therapeutic efficacy than conventional chemotherapy for stage IV breast cancer that could be used in the future.展开更多
Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well.Alternatively,the covalent conjugation of cyanine with...Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well.Alternatively,the covalent conjugation of cyanine with other potent therapeutic agents not only boosts its therapeutic efficacy but also broadens its therapeutic modality.Herein,we summarize miscellaneous cyanine-therapeutic agent conjugates in cancer theranostics from literature published between 2014 and 2020.The application scenarios of such theranostic cyanine conjugates covered common cancer therapeutic modalities,including chemotherapy,phototherapy and targeted therapy.Besides,cyanine conjugates that serve as nanocarriers for drug delivery are introduced as well.In an additional section,we analyze the potential of these conjugates for clinical translation.Overall,this review is aimed to stimulate research interest in exploring unattempted therapeutic agents and novel conjugation strategies and hopefully,accelerate clinical translation in this field.展开更多
Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features:such as non-toxicity,intravenous inject-ability,ability to cross the pulmonary capillary bed,and s...Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features:such as non-toxicity,intravenous inject-ability,ability to cross the pulmonary capillary bed,and significant enhancement of echo signals for the duration of the examination,resulting in essential preclinical and clinical applications.The use of microbubbles functional-ized with targeting ligands to bind to specific targets in the bloodstream has further enabled ultrasound molecular imaging.Nevertheless,it is very challenging to utilize targeted microbubbles for molecular imaging of extra-vascular targets due to their size.A series of acoustic nanomaterials have been developed for breaking free from this constraint.Especially,biogenic gas vesicles,gas-filled protein nanostructures from microorganisms,were engineered as thefirst biomolecular ultrasound contrast agents,opening the door for more direct visual-ization of cellular and molecular function by ultrasound imaging.The ordered protein shell structure and unique gasfilling mechanism of biogenic gas vesicles endow them with excellent stability and attractive acoustic responses.What’s more,their genetic encodability enables them to act as acoustic reporter genes.This article reviews the upgrading progresses of ultrasound contrast agents from microbubbles to biogenic gas vesicles,and the opportu-nities and challenges for the commercial and clinical translation of the nascentfield of biomolecular ultrasound.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.
基金supported by the College Students Extracur-ricular Innovation and Entrepreneurship Fund Project of Changzhou University(No.ZMF21020079)the Natural Sci-ence Fund for Colleges and Universities in Jiangsu Province(No.18KJB610001)+4 种基金the Natural Science Foundation of Jiangsu Province(No.BK20180964)the Science and Technology Project of Changzhou City(No.CJ20210119)the Natural Science Foun-dation of China(No.22075032)the National Key Research and Development Program(No.2021YFC3001104)the Natural Sci-ence Foundation of Xinjiang Uygur Autonomous Region(Nos.2020D01A49,2020D01B25 and 2020D01B26).
文摘To improve the selective separation performance of silica nanofibers(SiO_(2)NFs)for cesium ions(Cs+)and overcome the defects of Prussian blue nanoparticles(PB NPs),PB/SiO_(2)-NH_(2)NFs were prepared to remove Cs^(+)from water.Among them,3-aminopropyltriethoxysilane(APTES)underwent an alkylation reaction with SiO_(2),resulting in the formation of a dense Si-O-Si network structure that decorated the surface of SiO_(2)NFs.Meanwhile,the amino functional groups in APTES combined with Fe3+and then reacted with Fe2+to form PB NPs,which anchored firmly on the aminoated SiO_(2)NFs surface.In our experiment,the maxi-mumadsorption capacity of PB/SiO_(2)-NH_(2)NFs was 111.38 mg/g,which was 31.5mg/g higher than that of SiO_(2)NFs.At the same time,after the fifth cycle,the removal rate of Cs^(+)by PB/SiO_(2)-NH_(2)NFs adsorbent was 75.36%±3.69%.In addition,the adsorption isotherms and adsorption kinetics of PB/SiO_(2)-NH_(2)NFs were combined with the Freundlich model and the quasi-two-stage fitting model,respectively.Further mechanism analysis showed that the bond between PB/SiO_(2)-NH_(2)NFs and Cs^(+)was mainly a synergistic action of ion exchange,electrostatic adsorption and membrane separation.
基金supported by the National Natural Science Foundation of China(81371580 and 21273014)the National Natural Science Foundation for Distinguished Young Scholars(81225011)the State Key Program of National Natural Science of China(81230036)
文摘By adsorbing chitosan(CS)-functionalized Prussian blue(PB) nanoparticles(CS/PB NPs) complexing DNA onto the surface of gas encapsulated microbubbles(MBs), a multifunctional gene delivery system of MBs@CS/PB/DNA was fabricated for photothermally enhanced gene transfection through ultrasound-targeted microbubble destruction. CS/PB NPs of(2.69 ± 0.49) nm could complex DNA effectively when the mass ratio was2:1. It was found that MBs@CS/PB/DNA could enhance ultrasound imaging greatly both in vitro and in vivo. In addition, MBs@CS/PB/DNA could be disrupted by applying a higher-intensity ultrasound irradiation to release CS/PB/DNA, which could effectively transform the nearinfrared(NIR) light into heat to assist the uptake of CS/PB/DNA by cells. With the aid of ultrasound irradiation and NIR light irradiation, the gene transfection efficiency was significantly enhanced to(43.08 ± 1.13) %, much higher than polyethylenimine. Moreover, MBs@CS/PB/DNA showed excellent biocompatibility, encouraging the further exploration of MBs@CS/PB/DNA to be a platform for combined ultrasound image, photothermal therapy, drug delivery, and gene therapy.
基金supported by the National Key Research and Development Program of China(No.2016YFA0201400)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421004).
文摘Stage IV breast cancer,which has a high risk of invasion,often develops into metastases in distant organs,especially in the lung,and this could threaten the lives of women.Thus,the development of more advanced therapeutics that can efficiently target metastatic foci is crucial.In this study,we built an dual-acting therapeutic strategy using micelles with high stability functionalized with fibronectin-targeting CREKA peptides encapsulating two slightly soluble chemotherapy agents in water,doxorubicin(D)and vinorelbine(V),which we termed C-DVM.We found that small C-DVM micelles could efficiently codeliver drugs into 4T1 cells and disrupt microtubule structures.C-DVM also exhibited a powerful ability to eradicate and inhibit invasion of 4T1 cells.Moreover,an in vivo pharmacokinetics study showed that C-DVM increased the drug circulation half-life and led to increased enrichment of drugs in lung metastatic foci after 24 h.Moreover,dual-acting C-DVM treatment led to 90%inhibition of metastatic foci development and reduced invasion of metastases.C-DVM could potentially be used as a targeted treatment for metastasis and represents a new approach with higher therapeutic efficacy than conventional chemotherapy for stage IV breast cancer that could be used in the future.
基金financially supported by National Key Research and Development Program of China(No.2016YFA0201400)State Key Program of National Natural Science of China(No.81930047)+3 种基金Projects of International Cooperation and Exchanges NSFCPSF(No.31961143003)National Project for Research and Development of Major Scientific Instruments(No.81727803)Beijing Natural Science Foundation,Haidian,original innovation joint fund(No.17L20170)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421004).
文摘Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well.Alternatively,the covalent conjugation of cyanine with other potent therapeutic agents not only boosts its therapeutic efficacy but also broadens its therapeutic modality.Herein,we summarize miscellaneous cyanine-therapeutic agent conjugates in cancer theranostics from literature published between 2014 and 2020.The application scenarios of such theranostic cyanine conjugates covered common cancer therapeutic modalities,including chemotherapy,phototherapy and targeted therapy.Besides,cyanine conjugates that serve as nanocarriers for drug delivery are introduced as well.In an additional section,we analyze the potential of these conjugates for clinical translation.Overall,this review is aimed to stimulate research interest in exploring unattempted therapeutic agents and novel conjugation strategies and hopefully,accelerate clinical translation in this field.
基金financially supported by National Project for Research and Development of Major Scientific Instruments(No.81727803)National Natural Science Foundation of China(No.82071980),State Key Program of National Natural Science of China(No.81930047)Projects of International Cooperation and Exchanges NSFC-PSF(No.31961143003).
文摘Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features:such as non-toxicity,intravenous inject-ability,ability to cross the pulmonary capillary bed,and significant enhancement of echo signals for the duration of the examination,resulting in essential preclinical and clinical applications.The use of microbubbles functional-ized with targeting ligands to bind to specific targets in the bloodstream has further enabled ultrasound molecular imaging.Nevertheless,it is very challenging to utilize targeted microbubbles for molecular imaging of extra-vascular targets due to their size.A series of acoustic nanomaterials have been developed for breaking free from this constraint.Especially,biogenic gas vesicles,gas-filled protein nanostructures from microorganisms,were engineered as thefirst biomolecular ultrasound contrast agents,opening the door for more direct visual-ization of cellular and molecular function by ultrasound imaging.The ordered protein shell structure and unique gasfilling mechanism of biogenic gas vesicles endow them with excellent stability and attractive acoustic responses.What’s more,their genetic encodability enables them to act as acoustic reporter genes.This article reviews the upgrading progresses of ultrasound contrast agents from microbubbles to biogenic gas vesicles,and the opportu-nities and challenges for the commercial and clinical translation of the nascentfield of biomolecular ultrasound.