Cancer is a big challenge that has plagued the human beings for ages and one of the most effective treatments is chemotherapy. However, the low tumor-targeting ability limits the wide clinical application of chemother...Cancer is a big challenge that has plagued the human beings for ages and one of the most effective treatments is chemotherapy. However, the low tumor-targeting ability limits the wide clinical application of chemotherapy. The microenvironment plays a critical role in many aspects of tumor genesis. It generates the tumor vasculature and it is highly implicated in the progression to metastasis. To maintain a suitable environment for tumor progression, there are special microenvironment in tumor cell, such as low pH, high level of glutathione(GSH) and reactive oxygen species(ROS), and more special enzymes, which is different to normal cell. Microenvironment-targeted therapy strategy could create new opportunities for therapeutic targeting. Compared to other targeting strategies, microenvironment-targeted therapy strategy will control the drug release into tumor cells more accurately. Redox responsive drug delivery systems(DDSs) are developed based on the high level of GSH in tumor cells. However, there are also GSH in normal cell though its level is lower. In order to control the release of drugs more accurately and reduce side effects, other drug release stimuli have been introduced to redox responsive DDSs. Under the synergistic reaction of two stimuli, redox dual-stimuli responsive DDSs will control the release of drugs more accurately and quickly and even increase the accumulation. This review summarizes strategies of redox dual-stimuli responsive DDSs such as pH, light, enzyme, ROS, and magnetic guide to delivery chemotherapeutic agents more accurately, aiming at providing new ideas for further promoting the drug release,enhancing tumor-targeting and improving anticancer effects. To better illustrate the redox dual-stimuli responsive DDS, preparations of carriers are also briefly described in the review.展开更多
Due to better penetrating abilities of near-infrared (NIR) light and lower autofluorescence of biological tissue at NIR region, the combination of NIR fluorescent imaging with therapeutic abilities has gradually emerg...Due to better penetrating abilities of near-infrared (NIR) light and lower autofluorescence of biological tissue at NIR region, the combination of NIR fluorescent imaging with therapeutic abilities has gradually emerged as a promising strategy for cancer therapy. Herein, tumor microenvironment (TME) sensitive nanocarriers based on doxorubicin hydrochloride (DOX), NIR emitting carbon dots (C-dots), hollow mesoporous silica nanoparticles (HMSN) and anionic polymer citraconic anhydride-modified polylysine (PLL(cit)) are fabricated for imaging guided drug delivery. The NIR emitting C-dots were conjugated onto the surface of HMSN via disulfide bonds which can be reduced by intracellular glutathione (GSH) and result in the release of DOX into cells. And then the PLL(cit) was grafted on the surface of the nanocarriers to endow the nanocarriers with charge convertible property in mildly acidic TME (pH = 6.50) which results in prolonged blood circulation time and enhanced cellular internalization. The in vitro and in vivo experiments confirmed that the dual pH/GSH responsive features of nanocarriers can eliminate the tumor tissues effectively and elicit much slighter side effects. Moreover, since the fluorescence of C-dots can be recovered after the reduction of disulfide bonds and selectively accumulation of nanocarriers around tumor tissue, the DOX@HMSN-SS-C-dots-PLL(cit) can be served as a promising NIR fluorescence probe for targeted imaging of tumor tissue. As a kind of multifunctional nanocarrier with NIR fluorescent imaging and therapeutic functions, the theranostic nanocarriers hold great potential for tumor therapy and in vivo imaging of tumor tissue.展开更多
The hybridization of mechanically responsive molecular crystals with polymers has proven to be an efficient approach to fabricate smart hybrid materials that can produce multiple motions upon external stimulus actuati...The hybridization of mechanically responsive molecular crystals with polymers has proven to be an efficient approach to fabricate smart hybrid materials that can produce multiple motions upon external stimulus actuation.However,this fabrication approach occasionally displays limitations due to the solubility or poor dispersibility of molecular crystals in the polymer matrix solution.To address these challenges,we have created a facile and versatile strategy to use metal–organic frameworks(MOFs)as a protective coating against external perturbations while also improving the dispersibility of molecular crystals.As such,a series of hybrid smart materials with reversible photomechanical performance were successfully fabricated.Notably,the afforded smart materials can combine the photoresponsive properties of mechanically responsive molecular crystals with the vapor-responsive properties of certain polymers in one system,thereby obtaining dual-stimuli responsive actuators that can perform complicated motions(e.g.,crawling).These results pave the way for the fabrication of multistimuli responsive smart materials and broaden the applicable scope of MOFs.展开更多
Rheumatoid arthritis(RA)is a debilitating autoimmune disease that causes chronic pain and serious complications,presenting a significant challenge to treat.Promising approaches for treating RA involve signaling pathwa...Rheumatoid arthritis(RA)is a debilitating autoimmune disease that causes chronic pain and serious complications,presenting a significant challenge to treat.Promising approaches for treating RA involve signaling pathways modulation and targeted therapy.To this end,a multifunctional nanosystem,TPC-U@HAT,has been designed for RA therapy,featuring multitargeting,dual-stimuli response,and on-demand drug release capabilities.TPC-U@HAT is composed of a probe/prodrug TPC,a JAK1 kinase inhibitor upadacitinib,and the drug carrier HAT.TPC is composed of an aggregation-induced emission(AIE)-active NIR-II chromophore TPY and an NF-κB/NLRP3 inhibitor caffeic acid phenethyl ester(CAPE),connected via boronic ester bond which serves as the reactive-oxygen-species-responsive linker.The carrier,HAT,is created by grafting bone-targeting alendronate and hydrophobic tocopheryl succinate onto hyaluronic acid chains,which can encapsulate TPC and upadacitinib to form TPC-U@HAT.Upon intravenous injection into mice,TPC-U@HAT accumulates at inflamed lesions of RA through both active and passive targeting,and the overexpressed hyaluronidase and H_(2)O_(2) therein cleave the hyaluronic acid polymer chains and boronate bonds,respectively.This generates an AIE-active chromophore for detection and therapeutic evaluation of RA via both optoacoustic imaging and NIR-II fluorescent imaging and concomitantly releases CAPE and upadacitinib to exert efficacious therapy by inhibiting NF-κB/NLRP3 and JAK-STAT pathways.展开更多
Fluorescence imaging in the second infrared window(1000-1700 nm)has emerged as a promising approach to tumor diagnosis.However,the currently available second near-infrared(NIR-II)imaging agents are based on the“alway...Fluorescence imaging in the second infrared window(1000-1700 nm)has emerged as a promising approach to tumor diagnosis.However,the currently available second near-infrared(NIR-II)imaging agents are based on the“always on”modality or single biomarker activation,which are subject to limited imaging contrast,nonspecific response,and even false-positive diagnosis.Here,we developed a H2S/H+dual-stimuli responsive NIR-II fluorescent probe,WH-N3,for precise tumor delimitation and intraoperative fluorescence-guided surgical resection.WH-N3 itself is nonfluorescent,and it can only light up through synergistic activation by H2S and in the tumor acidic environment(TEM).Such a“duallock-dual-key”strategy-based activatable probe exhibited significantly higher tumor-to-normal tissue(T/N)ratios than the“always on”agent(ICG)and single parameter responsive counterpart probes in the imaging of colon tumors,which overexpresses H2S.WH-N3 was also able to visualize the tumor-derived endogenous H2S fluctuation and accurately differentiate tumor types based on H2S content discrepancy.More excitingly,under the guidance of the probe’s highly specific NIR-II fluorescence,a tiny orthotopic colon tumor with diameter down to 0.8 mm was facilely resected.We expect our dual-stimuli responsive strategy will contribute more reliable tools for specific discrimination and imaging-guided excision of tumor.展开更多
Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate fra...Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate framework-8 （ZIF-8）, a typical metal-organic framework （MOF）, is coated onto single gold nanorod （AuNR） core for successful realization of synergistic photothermal and chemotherapy triggered by near-infrared （NIR） light. Impressivel）~ high doxorubicin hydrochloride （DOX） loading capacity followed by pH and NIR light dual stimuli-responsive DOX release can be easily implemented through formation and breakage of coordination bonds in the system. Moreover, under NIR laser irradiation at 808 nm, these novel AuNR@MOF core-shell nanostructures exhibit effective synergistic chemo-photothermal therapy both in vitro and in vivo, confirmed by cell treatment and tumor ablation via intravenous injection.展开更多
In this paper, double hydrophilic ionic liquid block copolymers （ILBCs）, poly poly[1-methyl-3-（2-methacryloyloxy propylimidazolium bromine）]-block-（N.isopro. pylacrylamide） （PMMPImB-b-PNIPAAm） was first synthe...In this paper, double hydrophilic ionic liquid block copolymers （ILBCs）, poly poly[1-methyl-3-（2-methacryloyloxy propylimidazolium bromine）]-block-（N.isopro. pylacrylamide） （PMMPImB-b-PNIPAAm） was first synthesized by reversible addition- fragmentation chain transfer （RAFT） and then attached on the surface of gold nanoparticles （Au NPs） via a strong gold-sulfur bonding for preparing hybrid nanoparticles （PMMPImB-b-PNIPAAm-@-Au NPs）. The hybrid NPs had a three layers micelle-like structure, including a gold core, thermo-responsive inner shell and anion responsive outer corona. The self-assembling behavior of thermal- and anion-response from shell and corona were respectively investigated by change of temperature and addition of （CF3SO2）2N-. The results showed the hybrid NPs retained a stable dispersion beyond the lower critical solution temperature （LCST） because of the space or electrostatic protecting by outer PMMPImBo However, with increasing concentration of （CF3SO2）2N-, the micellization of self-assembling PMMPImB-b-PNIPAAm-@-Au NPs was induced to form micellar structure containing the core with hydrophobic PMMPImB- （CF3SO2）2N- surrounded by composite shell of Au NPs-PNIPAAm via the anion- responsive properties of ILBCs. These results indicated that the block copolymers protected plasmonic nanoparticles remain self-assembling properties of block copoly- mers when phase transition from outer corona polymer.展开更多
A biopolymer-inorganic hybrid system(MSN@PBLGF) is designed and fabricated from mesoporous silica nanoparticles(MSNs) and folic acid(FA)-terminated temperature-sensitive synthetic polypeptide,i.e.,poly(γ-benzyl-L-glu...A biopolymer-inorganic hybrid system(MSN@PBLGF) is designed and fabricated from mesoporous silica nanoparticles(MSNs) and folic acid(FA)-terminated temperature-sensitive synthetic polypeptide,i.e.,poly(γ-benzyl-L-glutamate)(PBLG) derivative,through a thiol-disulfide exchange reaction,where MSNs with high drug loading capacity serve as drug nanocarriers and the biocompatible PBLG biopolymer brushes installed on MSN surface through disulfide bonds endow the system with tumor-specific recognition ability and GSH/temperature dual-stimuli responsiveness.Controlled drug release experiments indicate that DOX can be tightly hosted in the system with limited premature release,but efficiently released in response to an increased concentration of GSH and/or an elevated temperature.Intracellular experiments demonstrate that the DOX-loaded MSN@PBLGF nanohybrid shows outstanding cellular uptake and cell-growth inhibition effects on human lung cancer cell line A549 in comparison with healthy human cells such as hepatocyte cells LO2.展开更多
基金National Natural Science Foundation of China (81202480,81302723)Natural Science Foundation of Liaoning Province (2015020749)。
文摘Cancer is a big challenge that has plagued the human beings for ages and one of the most effective treatments is chemotherapy. However, the low tumor-targeting ability limits the wide clinical application of chemotherapy. The microenvironment plays a critical role in many aspects of tumor genesis. It generates the tumor vasculature and it is highly implicated in the progression to metastasis. To maintain a suitable environment for tumor progression, there are special microenvironment in tumor cell, such as low pH, high level of glutathione(GSH) and reactive oxygen species(ROS), and more special enzymes, which is different to normal cell. Microenvironment-targeted therapy strategy could create new opportunities for therapeutic targeting. Compared to other targeting strategies, microenvironment-targeted therapy strategy will control the drug release into tumor cells more accurately. Redox responsive drug delivery systems(DDSs) are developed based on the high level of GSH in tumor cells. However, there are also GSH in normal cell though its level is lower. In order to control the release of drugs more accurately and reduce side effects, other drug release stimuli have been introduced to redox responsive DDSs. Under the synergistic reaction of two stimuli, redox dual-stimuli responsive DDSs will control the release of drugs more accurately and quickly and even increase the accumulation. This review summarizes strategies of redox dual-stimuli responsive DDSs such as pH, light, enzyme, ROS, and magnetic guide to delivery chemotherapeutic agents more accurately, aiming at providing new ideas for further promoting the drug release,enhancing tumor-targeting and improving anticancer effects. To better illustrate the redox dual-stimuli responsive DDS, preparations of carriers are also briefly described in the review.
基金This study was funded by National Natural Science Foundation of China (Nos. 51773055, 51973053, and 22073025)Natural Science Foundation of Hubei Province of China (No. 2019CFB748).
文摘Due to better penetrating abilities of near-infrared (NIR) light and lower autofluorescence of biological tissue at NIR region, the combination of NIR fluorescent imaging with therapeutic abilities has gradually emerged as a promising strategy for cancer therapy. Herein, tumor microenvironment (TME) sensitive nanocarriers based on doxorubicin hydrochloride (DOX), NIR emitting carbon dots (C-dots), hollow mesoporous silica nanoparticles (HMSN) and anionic polymer citraconic anhydride-modified polylysine (PLL(cit)) are fabricated for imaging guided drug delivery. The NIR emitting C-dots were conjugated onto the surface of HMSN via disulfide bonds which can be reduced by intracellular glutathione (GSH) and result in the release of DOX into cells. And then the PLL(cit) was grafted on the surface of the nanocarriers to endow the nanocarriers with charge convertible property in mildly acidic TME (pH = 6.50) which results in prolonged blood circulation time and enhanced cellular internalization. The in vitro and in vivo experiments confirmed that the dual pH/GSH responsive features of nanocarriers can eliminate the tumor tissues effectively and elicit much slighter side effects. Moreover, since the fluorescence of C-dots can be recovered after the reduction of disulfide bonds and selectively accumulation of nanocarriers around tumor tissue, the DOX@HMSN-SS-C-dots-PLL(cit) can be served as a promising NIR fluorescence probe for targeted imaging of tumor tissue. As a kind of multifunctional nanocarrier with NIR fluorescent imaging and therapeutic functions, the theranostic nanocarriers hold great potential for tumor therapy and in vivo imaging of tumor tissue.
基金The authors acknowledge the National Natural Science Foundation of China(no.21971126)111 Project(no.B12015).
文摘The hybridization of mechanically responsive molecular crystals with polymers has proven to be an efficient approach to fabricate smart hybrid materials that can produce multiple motions upon external stimulus actuation.However,this fabrication approach occasionally displays limitations due to the solubility or poor dispersibility of molecular crystals in the polymer matrix solution.To address these challenges,we have created a facile and versatile strategy to use metal–organic frameworks(MOFs)as a protective coating against external perturbations while also improving the dispersibility of molecular crystals.As such,a series of hybrid smart materials with reversible photomechanical performance were successfully fabricated.Notably,the afforded smart materials can combine the photoresponsive properties of mechanically responsive molecular crystals with the vapor-responsive properties of certain polymers in one system,thereby obtaining dual-stimuli responsive actuators that can perform complicated motions(e.g.,crawling).These results pave the way for the fabrication of multistimuli responsive smart materials and broaden the applicable scope of MOFs.
基金NSFC,Grant/Award Numbers:22274057,21875069,21788102Guangdong Provincial Basic and Applied Basic Research Fund Regional Joint Fund Project(Youth Fund Project),Grant/Award Number:2022A1515110842Chinese Postdoctoral Science Foundation,Grant/Award Number:2022M711194。
文摘Rheumatoid arthritis(RA)is a debilitating autoimmune disease that causes chronic pain and serious complications,presenting a significant challenge to treat.Promising approaches for treating RA involve signaling pathways modulation and targeted therapy.To this end,a multifunctional nanosystem,TPC-U@HAT,has been designed for RA therapy,featuring multitargeting,dual-stimuli response,and on-demand drug release capabilities.TPC-U@HAT is composed of a probe/prodrug TPC,a JAK1 kinase inhibitor upadacitinib,and the drug carrier HAT.TPC is composed of an aggregation-induced emission(AIE)-active NIR-II chromophore TPY and an NF-κB/NLRP3 inhibitor caffeic acid phenethyl ester(CAPE),connected via boronic ester bond which serves as the reactive-oxygen-species-responsive linker.The carrier,HAT,is created by grafting bone-targeting alendronate and hydrophobic tocopheryl succinate onto hyaluronic acid chains,which can encapsulate TPC and upadacitinib to form TPC-U@HAT.Upon intravenous injection into mice,TPC-U@HAT accumulates at inflamed lesions of RA through both active and passive targeting,and the overexpressed hyaluronidase and H_(2)O_(2) therein cleave the hyaluronic acid polymer chains and boronate bonds,respectively.This generates an AIE-active chromophore for detection and therapeutic evaluation of RA via both optoacoustic imaging and NIR-II fluorescent imaging and concomitantly releases CAPE and upadacitinib to exert efficacious therapy by inhibiting NF-κB/NLRP3 and JAK-STAT pathways.
基金This work was financially supported by the National Natural Science Foundation of China(grant no.21625503).The numerical calculations in this paper have been done on the supercomputing system in the Supercomputing Center of Wuhan University.
文摘Fluorescence imaging in the second infrared window(1000-1700 nm)has emerged as a promising approach to tumor diagnosis.However,the currently available second near-infrared(NIR-II)imaging agents are based on the“always on”modality or single biomarker activation,which are subject to limited imaging contrast,nonspecific response,and even false-positive diagnosis.Here,we developed a H2S/H+dual-stimuli responsive NIR-II fluorescent probe,WH-N3,for precise tumor delimitation and intraoperative fluorescence-guided surgical resection.WH-N3 itself is nonfluorescent,and it can only light up through synergistic activation by H2S and in the tumor acidic environment(TEM).Such a“duallock-dual-key”strategy-based activatable probe exhibited significantly higher tumor-to-normal tissue(T/N)ratios than the“always on”agent(ICG)and single parameter responsive counterpart probes in the imaging of colon tumors,which overexpresses H2S.WH-N3 was also able to visualize the tumor-derived endogenous H2S fluctuation and accurately differentiate tumor types based on H2S content discrepancy.More excitingly,under the guidance of the probe’s highly specific NIR-II fluorescence,a tiny orthotopic colon tumor with diameter down to 0.8 mm was facilely resected.We expect our dual-stimuli responsive strategy will contribute more reliable tools for specific discrimination and imaging-guided excision of tumor.
文摘Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate framework-8 （ZIF-8）, a typical metal-organic framework （MOF）, is coated onto single gold nanorod （AuNR） core for successful realization of synergistic photothermal and chemotherapy triggered by near-infrared （NIR） light. Impressivel）~ high doxorubicin hydrochloride （DOX） loading capacity followed by pH and NIR light dual stimuli-responsive DOX release can be easily implemented through formation and breakage of coordination bonds in the system. Moreover, under NIR laser irradiation at 808 nm, these novel AuNR@MOF core-shell nanostructures exhibit effective synergistic chemo-photothermal therapy both in vitro and in vivo, confirmed by cell treatment and tumor ablation via intravenous injection.
文摘In this paper, double hydrophilic ionic liquid block copolymers （ILBCs）, poly poly[1-methyl-3-（2-methacryloyloxy propylimidazolium bromine）]-block-（N.isopro. pylacrylamide） （PMMPImB-b-PNIPAAm） was first synthesized by reversible addition- fragmentation chain transfer （RAFT） and then attached on the surface of gold nanoparticles （Au NPs） via a strong gold-sulfur bonding for preparing hybrid nanoparticles （PMMPImB-b-PNIPAAm-@-Au NPs）. The hybrid NPs had a three layers micelle-like structure, including a gold core, thermo-responsive inner shell and anion responsive outer corona. The self-assembling behavior of thermal- and anion-response from shell and corona were respectively investigated by change of temperature and addition of （CF3SO2）2N-. The results showed the hybrid NPs retained a stable dispersion beyond the lower critical solution temperature （LCST） because of the space or electrostatic protecting by outer PMMPImBo However, with increasing concentration of （CF3SO2）2N-, the micellization of self-assembling PMMPImB-b-PNIPAAm-@-Au NPs was induced to form micellar structure containing the core with hydrophobic PMMPImB- （CF3SO2）2N- surrounded by composite shell of Au NPs-PNIPAAm via the anion- responsive properties of ILBCs. These results indicated that the block copolymers protected plasmonic nanoparticles remain self-assembling properties of block copoly- mers when phase transition from outer corona polymer.
基金the Jilin Province-University Cooperative Construction Project-Special Funds for New Materials (No. SXGJSF2017-3) for financial support
文摘A biopolymer-inorganic hybrid system(MSN@PBLGF) is designed and fabricated from mesoporous silica nanoparticles(MSNs) and folic acid(FA)-terminated temperature-sensitive synthetic polypeptide,i.e.,poly(γ-benzyl-L-glutamate)(PBLG) derivative,through a thiol-disulfide exchange reaction,where MSNs with high drug loading capacity serve as drug nanocarriers and the biocompatible PBLG biopolymer brushes installed on MSN surface through disulfide bonds endow the system with tumor-specific recognition ability and GSH/temperature dual-stimuli responsiveness.Controlled drug release experiments indicate that DOX can be tightly hosted in the system with limited premature release,but efficiently released in response to an increased concentration of GSH and/or an elevated temperature.Intracellular experiments demonstrate that the DOX-loaded MSN@PBLGF nanohybrid shows outstanding cellular uptake and cell-growth inhibition effects on human lung cancer cell line A549 in comparison with healthy human cells such as hepatocyte cells LO2.
