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Research Progress on the Bone Metastasis Mechanism of Prostate Cancer and Bone-Targeted Drugs
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作者 Xiaoqing Zhang Bifeng Fu +8 位作者 Ruiyu Mu Chunxin Jia Jiayu Li Haibo Xie Si Wu Ping Wang Aifeng Liu Guang Yang Xingyu Jiang 《Proceedings of Anticancer Research》 2024年第4期30-34,共5页
Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involv... Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involving multiple factors and steps.In recent years,with in-depth research on the mechanism of prostate cancer bone metastasis and the development of new drugs,important progress has been made in the treatment of prostate cancer bone metastasis.Based on this,this article introduces the mechanism of prostate cancer bone metastasis and the research progress of several bone-targeted drugs to provide reference and inspiration for future research. 展开更多
关键词 Prostate cancer Bone metastasis MECHANISM Bone targeting drugs Cancer cell
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Recent advances in lymphatic targeted drug delivery system for tumor metastasis 被引量:6
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作者 Xiao-Yu Zhang Wei-Yue Lu 《Cancer Biology & Medicine》 SCIE CAS CSCD 2014年第4期247-254,共8页
The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tu... The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers. 展开更多
关键词 Lymphatic metastatic tumor lymphatic system METASTASIS targeted drug delivery system LIPOSOME NANOPARTICLE polymermicelle (PM)
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Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel 被引量:2
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作者 Sara Hosayni Nasab Amin Amani +1 位作者 Hossein Ali Ebrahimi Ali Asghar Hamidi 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2021年第2期163-173,共11页
Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate si... Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy. 展开更多
关键词 PACLITAXEL SIRNA targeted drug delivery Magnetic nanoparticles Polymeric drug delivery
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Layered Double Hydroxide Modified by PEGylated Hyaluronic Acid as a Hybrid Nanocarrier for Targeted Drug Delivery 被引量:3
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作者 董岸杰 李雪 +6 位作者 王伟伟 韩尚聪 刘鉴锋 刘金剑 赵军强 许舒欣 邓联东 《Transactions of Tianjin University》 EI CAS 2016年第3期237-246,共10页
In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of ... In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5-FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of p Hdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed p H-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments. 展开更多
关键词 layered double hydroxide HA-PEG intercalation/adsorption controlled release targeted drug delivery
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Effective combinations of anti-cancer and targeted drugs for pancreatic cancer treatment
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作者 Arata Nishimoto 《World Journal of Gastroenterology》 SCIE CAS 2022年第28期3637-3643,共7页
Pancreatic cancer is highly aggressive and lethal.Due to the lack of effective methods for detecting the disease at an early stage,pancreatic cancer is frequently diagnosed late.Gemcitabine has been the standard chemo... Pancreatic cancer is highly aggressive and lethal.Due to the lack of effective methods for detecting the disease at an early stage,pancreatic cancer is frequently diagnosed late.Gemcitabine has been the standard chemotherapy drug for patients with pancreatic cancer for over 20 years,but its anti-tumor effect is limited.Therefore,FOLFIRINOX(leucovorin,fluorouracil,irinotecan,oxaliplatin)as well as combination therapies using gemcitabine and conventional agents,such as cisplatin and capecitabine,has also been administered;however,these have not resulted in complete remission.Therefore,there is a need to develop novel and effective therapies for pancreatic cancer.Recently,some studies have reported that combinations of gemcitabine and targeted drugs have had significant antitumor effects on pancreatic cancer cells.As gemcitabine induced DNA damage response,the proteins related to DNA damage response can be suitable additional targets for novel gemcitabine-based combination therapy.Furthermore,KRAS/RAF/MEK/ERK signaling triggered by oncogenic mutated KRAS and autophagy are frequently activated in pancreatic cancer.Therefore,these characteristics of pancreatic cancer are potential targets for developing effective novel therapies.In this minireview,combinations of gemcitabine and targeted drugs to these characteristics,combinations of targeted drugs,combinations of natural products and anti-cancer agents,including gemcitabine,and combinations among natural products are discussed. 展开更多
关键词 Pancreatic cancer GEMCITABINE targeted drug Combination therapy
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Performance Analysis of Magnetic Nanoparticles during Targeted Drug Delivery:Application of OHAM
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作者 Muhammad Zafar Muhammad Saif Ullah +6 位作者 Tareq Manzoor Muddassir Ali Kashif Nazar Shaukat Iqbal HabibUllah Manzoor Rizwan Haider Woo Young Kim 《Computer Modeling in Engineering & Sciences》 SCIE EI 2022年第2期723-749,共27页
In recent years,the emergence of nanotechnology experienced incredible development in the field of medical sciences.During the past decade,investigating the characteristics of nanoparticles during fluid flow has been ... In recent years,the emergence of nanotechnology experienced incredible development in the field of medical sciences.During the past decade,investigating the characteristics of nanoparticles during fluid flow has been one of the intriguing issues.Nanoparticle distribution and uniformity have emerged as substantial criteria in both medical and engineering applications.Adverse effects of chemotherapy on healthy tissues are known to be a significant concern during cancer therapy.A novel treatment method of magnetic drug targeting(MDT)has emerged as a promising topical cancer treatment along with some attractive advantages of improving efficacy,fewer side effects,and reduce drug dose.During magnetic drug targeting,the appropriate movement of nanoparticles(magnetic)as carriers is essential for the therapeutic process in the blood clot removal,infection treatment,and tumor cell treatment.In this study,we have numerically investigated the behavior of an unsteady blood flowinfused with magnetic nanoparticles during MDT under the influence of a uniform external magnetic field in a microtube.An optimal homotopy asymptotic method(OHAM)is employed to compute the governing equation for unsteady electromagnetohydrodynamics flow.The influence of Hartmann number(Ha),particle mass parameter(G),particle concentration parameter(R),and electro-osmotic parameter(k)is investigated on the velocity of magnetic nanoparticles and blood flow.Results obtained show that the electro-osmotic parameter,along with Hartmann’s number,dramatically affects the velocity of magnetic nanoparticles,blood flow velocity,and flow rate.Moreover,results also reveal that at a higher Hartman number,homogeneity in nanoparticles distribution improved considerably.The particle concentration andmass parameters effectively influence the capturing effect on nanoparticles in the blood flow using a micro-tube for magnetic drug targeting.Lastly,investigation also indicates that the OHAM analysis is efficient and quick to handle the system of nonlinear equations. 展开更多
关键词 Hartmann number magnetic nanoparticles nonlinear analysis targeted drug delivery optimal homotopy asymptotic method(OHAM)
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MOF-based magnetic microrobot swarms for pH-responsive targeted drug delivery
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作者 Qinyi Cao Yifan Zhang +3 位作者 Yanping Tang Changjin Wu Jizhuang Wang Dan Li 《Science China Chemistry》 SCIE EI CAS CSCD 2024年第4期1216-1223,共8页
Metal-organic frameworks(MOFs)hold significant potential as vehicles for drug delivery due to their expansive specific surface area,biocompatibility,and versatile attributes.Concurrently,magnetically actuated micro/na... Metal-organic frameworks(MOFs)hold significant potential as vehicles for drug delivery due to their expansive specific surface area,biocompatibility,and versatile attributes.Concurrently,magnetically actuated micro/nano-robots(MNRs)offer distinct advantages,such as untethered and precise manipulation.The fusion of these technologies presents a promising avenue for achieving non-invasive targeted drug delivery.Here,we report a MOF-based magnetic microrobot swarm(MMRS)for targeted therapy.Our approach overcomes limitations associated with a single MNR,including limited drug loading and the risk of loss during manipulation.We select Zeolitic Imidazolate Framework-8(ZIF-8)as the drug vehicle for its superior loading potential and p H-sensitive decomposition.Our design incorporates magnetic responsive components into the one-pot synthesis of Fe@ZIF-8,enabling collective behaviors under actuation.Tuning the yaw angle of alternating magnetic fields and nanoparticles'amount,the MMRSs with controllable size achieve instantaneous transformation among different configurations,including vortex-like swarms,chain-like swarms,and elliptical swarms,facilitating adaptation to environmental variations.Transported to the subcutaneous T24 tumor site,the MMRSs with encapsulated doxorubicin(DOX)automatically degrade and release the drug,leading to a dramatic reduction of the tumor in vivo.Our investigation signifies a significant advancement in the integration of biodegradable MOFs into microrobot swarms,ushering in new avenues for accurate and non-invasive targeted drug delivery. 展开更多
关键词 magnetic microrobot swarm MOF nanoparticles magnetic propulsion pH-responsive drug release targeted drug delivery
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Brain tumor-targeted drug delivery strategies 被引量:15
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作者 Xiaoli Wei Xishan Chen +1 位作者 Man Ying Weiyue Lu 《Acta Pharmaceutica Sinica B》 SCIE CAS 2014年第3期193-201,共9页
Despite the application of aggressive surgery,radiotherapy and chemotherapy in clinics,brain tumors are still a difficult health challenge due to their fast development and poor prognosis.Brain tumor-targeted drug del... Despite the application of aggressive surgery,radiotherapy and chemotherapy in clinics,brain tumors are still a difficult health challenge due to their fast development and poor prognosis.Brain tumor-targeted drug delivery systems,which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue,are a promising new approach to brain tumor treatments.Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues,potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery.In this review,we briefly describe the physiological characteristics of brain tumors,including blood–brain/brain tumor barriers,the tumor microenvironment,and tumor stem cells.We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges. 展开更多
关键词 Barriers targeting Tumor micro environment Tumor cells Systematic targeted drug delivery
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Cadmium nanoclusters in a protein matrix: Synthesis, characterization, and application in targeted drug delivery and cellular imaging 被引量:5
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作者 Morteza Sarparast Abolhassan Noori +7 位作者 Hoda Ilkhani S. Zahra Bathaie Maher F. EI-Kady Lisa J. Wang Huong Pham Kristofer L. Marsh Richard B. Kaner Mir F. Mousavi 《Nano Research》 SCIE EI CAS CSCD 2016年第11期3229-3246,共18页
Biotemplated metal nanoclusters have garnered much attention owing to their wide range of potential applications in biosensing, bioimaging, catalysis, and nanomedicine. Here, we report the synthesis of stable, biocomp... Biotemplated metal nanoclusters have garnered much attention owing to their wide range of potential applications in biosensing, bioimaging, catalysis, and nanomedicine. Here, we report the synthesis of stable, biocompatible, watersoluble, and highly fluorescent bovine serum albumin-templated cadmium nanoclusters (CdNcs) through a facile one-pot green method. We covalently conjugated hyaluronic acid (HA) to the CdNcs to form a pH-responsive, tumor- targeting theranostic nanocarrier with a sustained release profile for doxorubicin (DOX), a model anticancer drug. The nanocarrier showed a DOX encapsulation efficiency of about 75.6%. DOX release profiles revealed that 74% of DOX was released at pH 5.3, while less than 26% of DOX was released at pH 7.4 within the same 24-h period. The nanocarrier selectively recognized MCF-7 breast cancer cells expressing CD44, a cell surface receptor for HA, whereas no such recognition was observed with HA receptor-negative HEK293 cells. Biocompatibility of the nanocarrier was evaluated through cytotoxicity assays with HEK293 and MCF-7 ceils. The nanocarrier exhibited very low to no cytotoxicity, whereas the DOX-loaded nanocarrier showed considerable cellular uptake and enhanced MCF-7 breast cancer cell-killing ability. We also confirmed the feasibility of using the highly fluorescent nanoconjugate for bioimaging of MCF-7 and HeLa cells. The superior targeted drug delivery efficacy, cellular imaging capability, and low cytotoxicity position this nanoconjugate as an exciting new nanoplatform with promising biomedical applications. 展开更多
关键词 Cd nanoclusters hyaluronic acid targeted drug delivery fluorescence bioimaging NANOCARRIER
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Anti-tumor targeted drug delivery systems mediated by aminopeptidase N/CD13 被引量:4
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作者 Xun Wang Bin Wang Qiang Zhang 《Acta Pharmaceutica Sinica B》 SCIE CAS 2011年第2期80-83,共4页
Aminopeptidase N(APN)/CD13 is a transmembrane glycoprotein,which is overexpressed on tumor neovascular endothelial cells and most tumor cells,where it plays an important role in tumor angiogenesis.Peptides containing ... Aminopeptidase N(APN)/CD13 is a transmembrane glycoprotein,which is overexpressed on tumor neovascular endothelial cells and most tumor cells,where it plays an important role in tumor angiogenesis.Peptides containing the Asn-Gly-Arg(NGR)motif can specifically recognize APN/CD13 allowing them to act as tumor-homing peptides for the targeted delivery of anti-tumor drugs to tumor neovascular endothelial cells and tumor cells.This article reviews the literature and recent developments related to APN/CD13,its role in tumor growth and some antitumor drug delivery systems containing NGR peptides designed to target APN/CD13. 展开更多
关键词 Aminopeptidase N/CD13 NGR peptides ANTI-TUMOR targeted drug delivery system
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Macrophage membrane-coated nanovesicles for dual-targeted drug delivery to inhibit tumor and induce macrophage polarization 被引量:3
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作者 Xin Huang Lutong Wang +1 位作者 Haoyu Guo Weiyue Zhang 《Bioactive Materials》 SCIE CSCD 2023年第5期69-79,共11页
Background:Immunosuppressive M2 macrophages in the tumor microenvironment(TME)can mediate the therapeutic resistance of tumors,and seriously affect the clinical efficacy and prognosis of tumor patients.This study aims... Background:Immunosuppressive M2 macrophages in the tumor microenvironment(TME)can mediate the therapeutic resistance of tumors,and seriously affect the clinical efficacy and prognosis of tumor patients.This study aims to develop a novel drug delivery system for dual-targeting tumor and macrophages to inhibit tumor and induce macrophage polarization.Methods:The anti-tumor effects of methyltransferase like 14(METTL14)were investigated both in vitro and in vivo.The underlying mechanisms of METTL14 regulating macrophages were also explored in this study.We further constructed the cyclic(Arg-Gly-Asp)(cRGD)peptide modified macrophage membrane-coated nanovesicles to co-deliver METTL14 and the TLR4 agonist.Results:We found that METTL14 significantly inhibits the growth of tumor in vitro.METTL14 might downregulate TICAM2 and inhibit the Toll-like receptor 4(TLR4)pathway of macrophages,meanwhile,the combination of METTL14 and the TLR4 agonist could induce M1 polarization of macrophages.Macrophage membrane-coated nanovesicles are characterized by easy modification,drug loading,and dual-targeting tumor and macrophages,and cRGD modification can further enhance its targeting ability.It showed that the nanovesicles could improve the in vivo stability of METTL14,and dual-target tumor and macrophages to inhibit tumor and induce M1 polarization of macrophages.Conclusions:This study anticipates achieving the dual purposes of tumor inhibition and macrophage polarization,and providing a new therapeutic strategy for tumors. 展开更多
关键词 Cell membrane-coated nanovesicles targeted drug delivery system Tumor microenvironment Macrophage polarization OSTEOSARCOMA
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The feasibility of oral targeted drug delivery: Gut immune to particulates? 被引量:1
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作者 Yuehong Ren Wei Wu Xingwang Zhang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第6期2544-2558,共15页
Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantag... Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantages, attempts have been undertaken to complete an intravenous-to-oral conversion of targeted drug delivery. However, oral delivery of particulates to systemic circulation is highly challenging due to the biochemical aggressivity and immune exclusion in the gut that restrain absorption and access to the bloodstream. Little is known about the feasibility of targeted drug delivery via oral administration(oral targeting) to a remote site beyond the gastrointestinal tract. To this end, this review proactively contributes to a special dissection on the feasibility of oral targeting. We discussed the theoretical basis of oral targeting, the biological barriers of absorption, the in vivo fate and transport mechanisms of drug vehicles, and the effect of structural evolution of vehicles on oral targeting as well. At last, a feasibility analysis on oral targeting was performed based on the integration of currently available information. The innate defense of intestinal epithelium does not allow influx of more particulates into the peripheral blood through enterocytes. Therefore, limited evidence and lacking exact quantification of systemically exposed particles fail to support much success with oral targeting. Nevertheless, the lymphatic pathway may serve as a potentially alternative portal of peroral particles into the remote target sites via M-cell uptake. 展开更多
关键词 Oral targeted drug delivery Biological barriers In vivo fate Nanoparticles Transport mechanisms Delivery strategies Lymphatic transport FEASIBILITY
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A Network Meta-analysis of the Efficacy and Safety of Targeted Drug Combinations in the Treatment of Pulmonary Arterial Hypertension
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作者 Rui Wang Meng Wei +4 位作者 Jie Wang Xiang Huang Qianzhi Yan Shichao Wang Yun Wu 《Cardiology Discovery》 2023年第4期249-260,共12页
Objective:This network meta-analysis aims to compare the efficacy and safety of different targeted drug combination treatment for pulmonary arterial hypertension(PAH).Methods:Searches were conducted in Cochrane,PubMed... Objective:This network meta-analysis aims to compare the efficacy and safety of different targeted drug combination treatment for pulmonary arterial hypertension(PAH).Methods:Searches were conducted in Cochrane,PubMed,EMBASE,China National Knowledge Infrastructure,China Biomedical Literature Database,Wanfang Database,and ViP Chinese Science and Technology Journal Data to identify both published and unpublished randomized controlled trials from inception until January 1,2022.The risk of bias in the included studies was assessed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions.A network metaanalysis was performed using Stata 16.0 software.The efficacy and safety of different targeted drugs combined treatment for PAH were evaluated based on forest plot,funnel plot,and surface under the cumulative ranking.Results:A total of 29 randomized controlled trails with 4,448 patients treated with 10 different types of targeted drug combinations were included in this study.The results of the surface under the cumulative ranking showed that the combination regimen was the best clinical option to improve symptoms and delay progression in patients with pulmonary artery hypertension compared with monotherapy.Sildenafil in combination with ambrisentan significantly improved the 6-minute walk distance and reduced N-terminal pro-brain natriuretic peptide levels.Bosentan in combination with sildenafil significantly reduced mean pulmonary artery pressure,whereas bosentan in combination with epoprostenol was more effective than other combinations in reducing pulmonary vascular resistance.Bosentan in combination with tadalafil significantly improved the Borg dyspnea score,and bosentan in combination with iloprost was the best combination for improving World Health Organization functional class/New York Heart Association functional class.In terms of safety,there was no significant reduction in the incidence of adverse events,hospitalizations,or allcause mortality for combination therapy compared with monotherapy.Bosentan combined with sildenafil significantly reduced the risk of serious adverse events,but the risk of discontinuation due to an adverse event was higher than monotherapy.Sildenafil combined with epoprostenol reduced the risk of clinical worsening in patients with PAH.Conclusion:Compared with monotherapy,targeted drug combinations for PAH significantly improves exercise tolerance,pulmonary hemodynamic parameters,and reduces the risk of serious adverse events and clinical worsening in patients.Bosentan in combination with sildenafil and bosentan in combination with iloprost are combinations of targeted agents with significant efficacy and better safety profile than monotherapy for the treatment of PAH.Sildenafil in combination with epoprostenol has a low risk of clinical worsening in PAH. 展开更多
关键词 META-ANALYSIS Pulmonary arterial hypertension targeted drug TREATMENT
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Glucocorticoids-based prodrug design:Current strategies and research progress
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作者 Hongbing Liu Muse Ji +5 位作者 Peifu Xiao Jingxin Gou Tian Yin Haibing He Xing Tang Yu Zhang 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2024年第3期41-78,共38页
Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such a... Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and leukemia.However,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and cataract.These notorious side effects seriously compromise patients'quality of life,especially in patients with chronic diseases.Therefore,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention.Among them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising strategy.In this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so on.Besides,we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs.This review is expected to be helpful for the research and development of novel GCs and prodrugs. 展开更多
关键词 GLUCOCORTICOIDS Prodrug design targeted drug delivery Research progress
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Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension 被引量:1
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作者 Ji-Yao Sheng Zi-Fan Meng +1 位作者 Qiao Li Yong-Sheng Yang 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2024年第1期4-13,共10页
Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incide... Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension. 展开更多
关键词 Cirrhotic portal hypertension Target drug Primary prevention BLEEDING
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Staphylococcus aureus SoS response:Activation,impact,and drug targets
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作者 Kaiying Cheng Yukang Sun +3 位作者 Huan Yu Yingxuan Hu Yini He Yuanyuan Shen 《mLife》 CSCD 2024年第3期343-366,共24页
Staphylococcus aureus is a common cause of diverse infections,ranging from superficial to invasive,affecting both humans and animals.The widespread use of antibiotics in clinical treatments has led to the emergence of... Staphylococcus aureus is a common cause of diverse infections,ranging from superficial to invasive,affecting both humans and animals.The widespread use of antibiotics in clinical treatments has led to the emergence of antibiotic-resistant strains and small colony variants.This surge presents a significant challenge in eliminating infections and undermines the efficacy of available treatments.The bacterial Save Our Souls(Sos)response,triggered by genotoxic stressors,encompasses host immune defenses and antibiotics,playing a crucial role in bacterial survival,invasiveness,virulence,and drug resistance.Accumulating evidence underscores the pivotal role of the Sos response system in the pathogenicity of S.aureus.Inhibiting this system offers a promising approach for effective bactericidal treatments and curbing the evolution of antimicrobial re-sistance.Here,we provide a comprehensive review of the activation,impact,and key proteins associated with the Sos response in S.aureus.Additionally,perspectives on therapeutic strategies targeting the Sos response for S.aureus,both individually and in combination with traditional antibiotics are proposed. 展开更多
关键词 antibiotic-resistant drug target error-prone repair SoS response STAPHYLOCOCCUS
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In silico antiplasmodial effects of phytocompounds derived from Andrographis paniculata on validated drug targets of different stages of Plasmodium falciparum
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作者 Funmilayo I.D.Afolayan Sayo Ebenezer Oladokun 《Infectious Diseases Research》 2024年第2期1-11,共11页
Background:Andrographis paniculata has been widely reported as an herbal plant for malaria treatment.The increasing rate of resistance to recommended antimalarial drugs has justified the need for a continuous search f... Background:Andrographis paniculata has been widely reported as an herbal plant for malaria treatment.The increasing rate of resistance to recommended antimalarial drugs has justified the need for a continuous search for new and more potent drugs that target all stages of the Plasmodium falciparum life cycle from natural plant sources.This study aimed to determine the antiplasmodial effect of phytocompounds derived from A.paniculata on the stages of plasmodium falciparum.Methods:Phytocompounds from A.paniculata were identified by Gas Chromatography-Mass Spectrophotometry(GCMS)analysis.The phytocompounds were screened for their druggability using Lipinski’s rule of five and subjected to Absorption,Distribution,Metabolism,Excretion,Toxicity(ADMET)and druglikeness analysis.The phytocompounds were docked against some validated drug targets at different stages of Plasmodium falciparum(hepatic,asexual,sexual,and vector targets)using PyRx software to analyze the inhibitory potential and protein-ligand interaction.Thereafter,the stability and flexibility of the best complexes were assessed through molecular dynamics simulations at 50ns using WebGRO.Result:The 7a-Isopropenyl-4,5-dimethyloctahydroinden-4-yl exhibited a higher binding affinity and better stability throughout the simulation period with P.falciparum dihydrofolate reductase-thymidylate synthase and Plasmodium falciparum M1 alanyl aminopeptidase for asexual blood stage and gametocyte stage of Plasmodium falciparum,respectively than the existing drugs.Meanwhile,N-Ethyl-3-methoxy-4-methylphenethylamine was also found to have a higher binding affinity and more stability throughout the simulation period with P.falciparum purine nucleoside phosphorylase and Plasmodium falciparum gametocyte surface protein for Hepatic schizonts stage of Plasmodium falciparum and gametocyte transmission blocking stage,respectively,than the existing drugs.Conclusion:The 7a-Isopropenyl-4,5-dimethyloctahydroinden-4-yl and N-Ethyl-3-methoxy-4 methylphenethylamine from A.paniculata are predicted as an antimalarial drug candidate.Thus,it is recommended that in vitro and in vivo bioassays be conducted on these hit compounds to validate these predictions. 展开更多
关键词 Plasmodium falciparum drug targets Andrographis paniculata molecular docking molecular dynamics
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Targeting capabilities of engineered extracellular vesicles for the treatment of neurological diseases
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作者 Xinyu Yang Xiangyu Gao +2 位作者 Xiaofan Jiang Kangyi Yue Peng Luo 《Neural Regeneration Research》 SCIE CAS 2025年第11期3076-3094,共19页
Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–b... Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field. 展开更多
关键词 Alzheimer's disease amyotrophic lateral sclerosis engineered extracellular vesicles GLIOMA ischemic stroke neurological diseases Parkinson's disease PSYCHOSIS targeted drug delivery traumatic brain injury
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A Study on the Multi-Compartment Linear Circulation Pharmacokinetic Model for the Targeting Drug Delivery System
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作者 张志荣 永井恒司 《Journal of Chinese Pharmaceutical Sciences》 CAS 1996年第2期81-87,共7页
By analyzing the observed phenomena and the data collected in the study, a multi-compartment linear circulation model for targeting drug delivery system was developed and the function formulas of the drug concentratio... By analyzing the observed phenomena and the data collected in the study, a multi-compartment linear circulation model for targeting drug delivery system was developed and the function formulas of the drug concentration-time in blood and target organ by computing were figured out. The drug concentration-time curve for target organ can be plotted with reference to the data of drug concentration in blood according to the model. The pharmacokinetic parameters of the drug in target organ could also be obtained. The practicability of the model was further checked by the curves of drug concentration-time in blood and target organ(liver) of liver-targeting nanoparticles in animal tests. Based on the liver drug concentration-time curves calculated by the function formula of the drug in target organ, the pharmacokinetic behavior of the drug in target organ(liver) was analyzed by statistical moment, and its pharmacokinetic parameters in liver were obtained. It is suggested that the (relative targeting index( can be used for quantitative evaluation of the targeting drug delivery systems. 展开更多
关键词 Pharmacokinetic model for targeting drug delivery systems Multi-compartment linear circulation pharmacokinetic model Relative targeting index
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Anti-cancer drugs targeting using nanocarrier niosomes-a review
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作者 Sidharth Mehta 《TMR Cancer》 2020年第4期169-174,共6页
In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them ... In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells. 展开更多
关键词 NANOCARRIERS NIOSOMES Anticancer drugs targeted drug delivery Non-ionic surfactants vesicles Anti neoplastic agents
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