Glutathione-responsive carboxymethyl chitosan nanoparticles cross-linked with disulfide bonds were developed for controlled release of herbicides. The nanoparticles were synthesized by selfassembly of amphiphilic carb...Glutathione-responsive carboxymethyl chitosan nanoparticles cross-linked with disulfide bonds were developed for controlled release of herbicides. The nanoparticles were synthesized by selfassembly of amphiphilic carboxymethyl chitosan derivative (CMCS-MUA) in aqueous solution and subsequently producing disulfide cross-linking bonds by ultrasonic treatment. TEM showed that the nanoparticles had a spherical core-shell configuration with a size of about 250 nm. Assessment of stability of the nanoparticles (considering mean diameter, polydispersity, and Zeta potential) was conducted over a period of three months, and the nanoparticles were found to be stable in solution. Herbicide-loaded nanoparticles were prepared using diuron as a model herbicide. In vitro release study revealed that diuron can be released from nanoparticles in a controlled manner depended on the glutathione concentration. Herbicidal activity assays performed with preemergence treatment of target species (Echinochloa crusgalli) showed the effectiveness of diuron- loaded nanoparticles. Assays with nontarget species (Zea mays) showed that the diuronloaded nanoparticles did not affect plant growth. The results indicate that the glutathioneresponsive nanoparticles prepared in this work will be a promising candidate for controlled release of herbicides in agriculture.展开更多
Melanoma,as the most aggressive and treatment-resistant skin malignancy,is responsible for about 80%of all skin cancer mortalities.Prone to invade into the dermis and form distant metastases significantly reduce the p...Melanoma,as the most aggressive and treatment-resistant skin malignancy,is responsible for about 80%of all skin cancer mortalities.Prone to invade into the dermis and form distant metastases significantly reduce the patient survival rate.Therefore,early treatment of the melanoma in situ or timely blocking the deterioration of metastases is critical.In this study,a sulfur dioxide(SO_(2))polymer prodrug was designed as both an intracellular glutathione(GSH)-responsive SO_(2) generator and a carrier of doxorubicin(DOX),and used for the treatment of subcutaneous and metastatic melanoma.Firstly,chemical conjugation of 4-N-(2,4-dinitrobenzenesulfonyl)-imino-1-butyric acid(DIBA)onto the side chains of methoxy poly(ethylene glycol)grafted dextran(mPEG-g-Dex)resulted in the synthesis of the amphiphilic polymer prodrug of SO_(2),mPEG-g-Dex(DIBA).The obtained mPEG-g-Dex(DIBA)could self-assemble into stable micellar nanoparticles and exhibited a glutathione-responsive SO_(2) release behavior.Subsequently,DOX was encapsulated into the core of mPEG-g-Dex(DIBA)micelles to form DOX-loaded nanoparticles(PDDN-DOX).The formed PDDN-DOX could be internalized by B16F10 cells and synchronously release DOX and SO_(2) into the tumor cells.As a result,PDDN-DOX exerted synergistic anti-tumor effects in B16F10 melanoma cells because of the oxidative damage properties of SO_(2) and toxic effects of DOX.Furthermore,in vivo experiments verified that PDDN-DOX had great potential for the treatment of subcutaneous and metastasis melanoma.Collectively,our present work demonstrates that the combination of SO_(2)-based gas therapy and chemotherapeutics offers a new avenue for inhibiting melanoma progression and metastases.展开更多
Although photothermal therapy(PTT) has emerged as an appealing strategy for cancer treatment, the development of photothermal agents capable of precisely controlling temperature remains a challenge. In this paper, we ...Although photothermal therapy(PTT) has emerged as an appealing strategy for cancer treatment, the development of photothermal agents capable of precisely controlling temperature remains a challenge. In this paper, we present a novel synthetic photosensitizer based on a sulfur-substituted hemicyanine. It was discovered that replacing an oxygen atom in a hemicyanine derivative with a sulfur atom significantly enhances photothermal efficiency and enables lysosome targeting in cancer cells.More importantly, because of the rigid planer structure of the sulfur-substituted hemicyanine, which differs from traditional photothermal agents(PTAs) based on twisted intramolecular charge transfer(TICT) or group rotation mechanisms, the efficiency of photothermal conversion is not affected by intracellular viscosity, allowing precise temperature control during PTT.Further modifying the agent with a glutathione-responsive moiety allows the PTAs to be activated only in cancer cells. The newly proposed PTA achieves efficient PTT in a tumor-bearing mouse model while having negligible toxic side effects on healthy tissues.展开更多
Stimuli-responsive delivery systems hold promise in cancer treatments.However,their application potential has been limited due to undesirable drug leaking during blood circulation and inefficient therapeutic efficacy ...Stimuli-responsive delivery systems hold promise in cancer treatments.However,their application potential has been limited due to undesirable drug leaking during blood circulation and inefficient therapeutic efficacy in tumors,resulting in undesirable therapeutic outcomes.Herein,we have developed a novel redox-sensitive pegylated phospholipid,termed as DOPE-SS-PEG,which can form a glutathione(GSH)-triggered precision explosive system(GPS)for simultaneously improving circulation stability,tumor specificity,and chemosensitivity,leading to explosive anticancer effects.GPS is constructed of liposomal doxorubicin(DOX)functionalized with DOPE-SS-PEG and MnO_(2) nanoparticles,which can protect liposome structure in the presence of serum GSH(20μM),whereas converts to cationic liposome in response to intracellular GSH(10 mM),thereby enhancing circulation stability,tumor specificity,endosomal escape,and cytoplasmic delivery.Importantly,GPS can not only generate oxygen to relieve hypoxia and consequently enhance chemosensitivity,but quench GSH antioxidability to elevate the accruement of intracellular reactive oxygen species(ROS),leading to an explosion of oxidative stress induced cell injury.Particularly,in vivo studies show that GPS selectively accumulates in tumor tissues,effectively inhibits tumor growth,exhibits minimal systemic adverse effects,and consequently prolongs the survival time of tumor-bearing mice.Therefore,GPS is a unique stimuli-responsive treatment with programmed and on-demand drug delivery,as well as explosive therapeutic efficacy,and provides an intelligent anticancer treatment.展开更多
文摘Glutathione-responsive carboxymethyl chitosan nanoparticles cross-linked with disulfide bonds were developed for controlled release of herbicides. The nanoparticles were synthesized by selfassembly of amphiphilic carboxymethyl chitosan derivative (CMCS-MUA) in aqueous solution and subsequently producing disulfide cross-linking bonds by ultrasonic treatment. TEM showed that the nanoparticles had a spherical core-shell configuration with a size of about 250 nm. Assessment of stability of the nanoparticles (considering mean diameter, polydispersity, and Zeta potential) was conducted over a period of three months, and the nanoparticles were found to be stable in solution. Herbicide-loaded nanoparticles were prepared using diuron as a model herbicide. In vitro release study revealed that diuron can be released from nanoparticles in a controlled manner depended on the glutathione concentration. Herbicidal activity assays performed with preemergence treatment of target species (Echinochloa crusgalli) showed the effectiveness of diuron- loaded nanoparticles. Assays with nontarget species (Zea mays) showed that the diuronloaded nanoparticles did not affect plant growth. The results indicate that the glutathioneresponsive nanoparticles prepared in this work will be a promising candidate for controlled release of herbicides in agriculture.
基金supported by the National Natural Science Foundation of China(51803209,51773196,and 51573184)the Jilin Provincial Science and Technology Development Program(20190201205JC,20190103022JH,and 20190103038JH)the Youth Innovation Promotion Association of Chinese Academy and Sciences(2017266).
文摘Melanoma,as the most aggressive and treatment-resistant skin malignancy,is responsible for about 80%of all skin cancer mortalities.Prone to invade into the dermis and form distant metastases significantly reduce the patient survival rate.Therefore,early treatment of the melanoma in situ or timely blocking the deterioration of metastases is critical.In this study,a sulfur dioxide(SO_(2))polymer prodrug was designed as both an intracellular glutathione(GSH)-responsive SO_(2) generator and a carrier of doxorubicin(DOX),and used for the treatment of subcutaneous and metastatic melanoma.Firstly,chemical conjugation of 4-N-(2,4-dinitrobenzenesulfonyl)-imino-1-butyric acid(DIBA)onto the side chains of methoxy poly(ethylene glycol)grafted dextran(mPEG-g-Dex)resulted in the synthesis of the amphiphilic polymer prodrug of SO_(2),mPEG-g-Dex(DIBA).The obtained mPEG-g-Dex(DIBA)could self-assemble into stable micellar nanoparticles and exhibited a glutathione-responsive SO_(2) release behavior.Subsequently,DOX was encapsulated into the core of mPEG-g-Dex(DIBA)micelles to form DOX-loaded nanoparticles(PDDN-DOX).The formed PDDN-DOX could be internalized by B16F10 cells and synchronously release DOX and SO_(2) into the tumor cells.As a result,PDDN-DOX exerted synergistic anti-tumor effects in B16F10 melanoma cells because of the oxidative damage properties of SO_(2) and toxic effects of DOX.Furthermore,in vivo experiments verified that PDDN-DOX had great potential for the treatment of subcutaneous and metastasis melanoma.Collectively,our present work demonstrates that the combination of SO_(2)-based gas therapy and chemotherapeutics offers a new avenue for inhibiting melanoma progression and metastases.
基金supported by the National Natural Science Foundation of China(21925802,21878039,22022803,22078046)the NSFC-Liaoning United Fund(U1908202)the National Key Research and Development Plan(2018AAA0100301)。
文摘Although photothermal therapy(PTT) has emerged as an appealing strategy for cancer treatment, the development of photothermal agents capable of precisely controlling temperature remains a challenge. In this paper, we present a novel synthetic photosensitizer based on a sulfur-substituted hemicyanine. It was discovered that replacing an oxygen atom in a hemicyanine derivative with a sulfur atom significantly enhances photothermal efficiency and enables lysosome targeting in cancer cells.More importantly, because of the rigid planer structure of the sulfur-substituted hemicyanine, which differs from traditional photothermal agents(PTAs) based on twisted intramolecular charge transfer(TICT) or group rotation mechanisms, the efficiency of photothermal conversion is not affected by intracellular viscosity, allowing precise temperature control during PTT.Further modifying the agent with a glutathione-responsive moiety allows the PTAs to be activated only in cancer cells. The newly proposed PTA achieves efficient PTT in a tumor-bearing mouse model while having negligible toxic side effects on healthy tissues.
基金This work were supported by the National Key Research and Development Program of China(No.2019YFA0802800)the National Key Research and Development Program of China(No.2018YFB1105400)+3 种基金the National Natural Science Foundation of China(No.21472090)the Natural Science Foundation of Jiangsu Province(No.BK20180334)the Fundamental Research Funds for Central Universities Nanjing University,the Scientific Research Foundation of Graduate School of Nanjing University(No.2018CL12)The Key Research and Development Program of Jiangsu Provincial Department of Science and Technology of China(No.BE2019002).
文摘Stimuli-responsive delivery systems hold promise in cancer treatments.However,their application potential has been limited due to undesirable drug leaking during blood circulation and inefficient therapeutic efficacy in tumors,resulting in undesirable therapeutic outcomes.Herein,we have developed a novel redox-sensitive pegylated phospholipid,termed as DOPE-SS-PEG,which can form a glutathione(GSH)-triggered precision explosive system(GPS)for simultaneously improving circulation stability,tumor specificity,and chemosensitivity,leading to explosive anticancer effects.GPS is constructed of liposomal doxorubicin(DOX)functionalized with DOPE-SS-PEG and MnO_(2) nanoparticles,which can protect liposome structure in the presence of serum GSH(20μM),whereas converts to cationic liposome in response to intracellular GSH(10 mM),thereby enhancing circulation stability,tumor specificity,endosomal escape,and cytoplasmic delivery.Importantly,GPS can not only generate oxygen to relieve hypoxia and consequently enhance chemosensitivity,but quench GSH antioxidability to elevate the accruement of intracellular reactive oxygen species(ROS),leading to an explosion of oxidative stress induced cell injury.Particularly,in vivo studies show that GPS selectively accumulates in tumor tissues,effectively inhibits tumor growth,exhibits minimal systemic adverse effects,and consequently prolongs the survival time of tumor-bearing mice.Therefore,GPS is a unique stimuli-responsive treatment with programmed and on-demand drug delivery,as well as explosive therapeutic efficacy,and provides an intelligent anticancer treatment.
