"Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in t..."Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in threedimensional culture.As an angiogenesis-independent pathway,VM and/or periodic acid-schiff-positive patterns are associated with poor prognosis in tumor patients.Moreover,VM is resistant to angiogenesis inhibitors.Here,we will review the advances in research on biochemical and molecular signaling pathways of VM in tumors and on potential anti-VM therapy strategy.展开更多
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
Amino acid transporters,which play a vital role in transporting amino acids for the biosynthesis of mammalian cells,are highly expressed in types of tumors.Increasing studies have shown the feasibility of amino acid t...Amino acid transporters,which play a vital role in transporting amino acids for the biosynthesis of mammalian cells,are highly expressed in types of tumors.Increasing studies have shown the feasibility of amino acid transporters as a component of tumortargeting therapy.In this review,we focus on tumor-related amino acid transporters and their potential use in tumor-targeting therapy.Firstly,the expression characteristics of amino acid transporters in cancer and their relationship with tumor growth are reviewed.Secondly,the recognition requirements are discussed,focusing on the“acidbase”properties,conformational isomerism and structural analogues.Finally,recent developments in amino acid transporter-targeting drug delivery strategies are highlighted,including prodrugs and nanocarriers,with special attention to the latest findings of molecular mechanisms and targeting efficiency of transporter-mediated endocytosis.We aim to offer related clues that might lead to valuable tumor-targeting strategies by the utilization of amino acid transporters.展开更多
Phage display technique provides a powerful approach for the discovery of new tumor-specific peptides.However,the peptides isolated through this technique usually did not possess high tumor-specific property.A pre-cle...Phage display technique provides a powerful approach for the discovery of new tumor-specific peptides.However,the peptides isolated through this technique usually did not possess high tumor-specific property.A pre-clearing step was introduced to increase the efficiency of biopanning by removal of particles that could interact with ubiquitously expressed cellular receptors in the non-target organs.The randomized Ph.D-CX7C phage library (Phage III) was first pre-cleared in normal mice to reduce vasculatureor organ-targeting phages to get the pre-cleared phage library,and then the tumor-targeting bacteriophage particles (Phage I) were screened from pre-clearing phage library in S180 tumor-bearing mice.The biodistribution results of 99mTc-labeled phages in mice bearing S180 tumor show that the uptake of 99mTc-labeled Phage I in tumor is high but low in normal organs,and the tumor-to-liver and tumor-to-spleen ratios of 99mTc-labeled Phage I are higher than those of 99mTc-labeled Phage II (tumor-specific phages screened from the original CX7C library) and Phage III (unscreened phages from the original CX7C library).It indicates that the yield of tumor-targeting bacteriophage particles could be improved and the non-specific binding in organs becomes weak.Consequently,the pre-clearing phage display method could improve the yield of positive hits by reducing the non-target organ accumulation of bacteriophage particles.展开更多
Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative bre...Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative breast cancer(TNBC).However,the relatively low anti-tumor immune response rate and ICIs drug resistance highlight the necessity of developing ICIs combination therapy strategies to improve the anti-tumor effect of immunotherapy.Herein,the immunomodulator epigallocatechin gallate palmitate(PEGCG)and the immunoadjuvant metformin(MET)self-assembled into tumor-targeted micelles via hydrogen bond and electrostatic interaction,which encapsulated the therapeutic agents doxorubicin(DOX)-loaded PEGCG-MET micelles(PMD)and combined with ICIs(anti-PD-1 antibody)as therapeutic strategy to reduce the endogenous expression of PD-L1 and improve the tumor immunosuppressive microenvironment.The results presented that PMD integrated chemotherapy and immunotherapy to enhance antitumor efficacy in vitro and in vivo,compared with DOX or anti-PD-1 antibody for the therapy of TNBC.PMD micelles might be a potential candidate,which could remedy the shortcomings of antibody-based ICIs and provide synergistic effect to enhance the antitumor effects of ICIs in tumor therapy.展开更多
Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory responses....Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory responses.In this study,we present a novel tumor-targeting nano-adjuvant termed aPDL1-PLG/R848 NPs,which are composed of aPDL1 antibody,Fc-III-4C peptide linker(Fc-linker)and poly(L-glutamic acid)-grafted-R848.Under ultrasound irradiation,antigen-presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants.The strategy inhibits primary tumor growth and induces a strong antigen-specific immune memory effect to prevent tumor recurrence in vivo.This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy.展开更多
目的通过文献计量学研究展示肾癌靶向治疗领域的现状、热点和前沿,为探索新的靶向策略提供参考。方法在Web of Science数据库核心合集(Web of Science Core Collection,WoSCC)中检索2009-2022年发表的相关文献1718篇及其记录的信息,采用...目的通过文献计量学研究展示肾癌靶向治疗领域的现状、热点和前沿,为探索新的靶向策略提供参考。方法在Web of Science数据库核心合集(Web of Science Core Collection,WoSCC)中检索2009-2022年发表的相关文献1718篇及其记录的信息,采用Citespace、R及Scimago Graphica软件进行文献计量学分析与可视化。结果美国出版物数量(414篇,24.10%)、出版物引用次数(20302次)及中介中心性(betweenness centrality,BC)(0.45)排名第1,对研究的贡献最大。美国印第安纳大学的CHENG L是最多产的研究人员(22篇),斯隆凯特琳癌症中心为研究产量最多的机构(38篇),Cancers为刊发研究最多的期刊(56篇)。目前的研究热点主要包括血管生成、肿瘤微环境(tumor microenvironment,TME)、靶向药物释放系统等。上皮间充质转换(epithelial-mesenchymal transition,EMT)、免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)、肿瘤侵袭与扩散是该领域的研究前沿,正在不断发展。结论本项文献计量分析为肾癌靶向治疗的研究趋势,为相关热点及新兴前沿提供重要见解。本研究为寻求合作者的研究人员提供了有用的资源,并为未来研究提供参考。展开更多
基金Supported by A grant from the National Nature Science Foundation of China,No. 30672073
文摘"Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in threedimensional culture.As an angiogenesis-independent pathway,VM and/or periodic acid-schiff-positive patterns are associated with poor prognosis in tumor patients.Moreover,VM is resistant to angiogenesis inhibitors.Here,we will review the advances in research on biochemical and molecular signaling pathways of VM in tumors and on potential anti-VM therapy strategy.
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 work was supported by the National Natural Science Foundation of China(Nos.81803442 and 81703425).
文摘Amino acid transporters,which play a vital role in transporting amino acids for the biosynthesis of mammalian cells,are highly expressed in types of tumors.Increasing studies have shown the feasibility of amino acid transporters as a component of tumortargeting therapy.In this review,we focus on tumor-related amino acid transporters and their potential use in tumor-targeting therapy.Firstly,the expression characteristics of amino acid transporters in cancer and their relationship with tumor growth are reviewed.Secondly,the recognition requirements are discussed,focusing on the“acidbase”properties,conformational isomerism and structural analogues.Finally,recent developments in amino acid transporter-targeting drug delivery strategies are highlighted,including prodrugs and nanocarriers,with special attention to the latest findings of molecular mechanisms and targeting efficiency of transporter-mediated endocytosis.We aim to offer related clues that might lead to valuable tumor-targeting strategies by the utilization of amino acid transporters.
文摘Phage display technique provides a powerful approach for the discovery of new tumor-specific peptides.However,the peptides isolated through this technique usually did not possess high tumor-specific property.A pre-clearing step was introduced to increase the efficiency of biopanning by removal of particles that could interact with ubiquitously expressed cellular receptors in the non-target organs.The randomized Ph.D-CX7C phage library (Phage III) was first pre-cleared in normal mice to reduce vasculatureor organ-targeting phages to get the pre-cleared phage library,and then the tumor-targeting bacteriophage particles (Phage I) were screened from pre-clearing phage library in S180 tumor-bearing mice.The biodistribution results of 99mTc-labeled phages in mice bearing S180 tumor show that the uptake of 99mTc-labeled Phage I in tumor is high but low in normal organs,and the tumor-to-liver and tumor-to-spleen ratios of 99mTc-labeled Phage I are higher than those of 99mTc-labeled Phage II (tumor-specific phages screened from the original CX7C library) and Phage III (unscreened phages from the original CX7C library).It indicates that the yield of tumor-targeting bacteriophage particles could be improved and the non-specific binding in organs becomes weak.Consequently,the pre-clearing phage display method could improve the yield of positive hits by reducing the non-target organ accumulation of bacteriophage particles.
基金the projects of the National Key Research and Development Program(No.2021YFA0716702)the National Natural Science Foundation of China(Nos.61805122,22022404 and 22074050)+5 种基金Green Industry Science and Technology Leading Project of Hubei University of Technology(No.XJ2021003301)the National Natural Science Foundation of Hubei Province(No.2022CFA033)supported by Chinese Society of Clinical Oncology(CSCO)supported by Jiangsu Hengrui Cancer Research Foundation(No.YHR2019–0325)supported by the Fundamental Research Funds for the Central Universities(No.CCNU22QN007)supported by the Opening Fund from the Jiangsu Key Laboratory of Medical Optics,Suzhou Institute of Biomedical Engineering and Technology(No.JKLMO202203)supported by the Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science,MO(No.M2022–5).
文摘Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative breast cancer(TNBC).However,the relatively low anti-tumor immune response rate and ICIs drug resistance highlight the necessity of developing ICIs combination therapy strategies to improve the anti-tumor effect of immunotherapy.Herein,the immunomodulator epigallocatechin gallate palmitate(PEGCG)and the immunoadjuvant metformin(MET)self-assembled into tumor-targeted micelles via hydrogen bond and electrostatic interaction,which encapsulated the therapeutic agents doxorubicin(DOX)-loaded PEGCG-MET micelles(PMD)and combined with ICIs(anti-PD-1 antibody)as therapeutic strategy to reduce the endogenous expression of PD-L1 and improve the tumor immunosuppressive microenvironment.The results presented that PMD integrated chemotherapy and immunotherapy to enhance antitumor efficacy in vitro and in vivo,compared with DOX or anti-PD-1 antibody for the therapy of TNBC.PMD micelles might be a potential candidate,which could remedy the shortcomings of antibody-based ICIs and provide synergistic effect to enhance the antitumor effects of ICIs in tumor therapy.
基金Ministry of Science and Technology of China,Grant/Award Number:2022YFE0110200Natural Science Foundation of Jilin Province,Grant/Award Number:20230101037JCNational Natural Science Foundation of China,Grant/Award Numbers:52203198,52025035。
文摘Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory responses.In this study,we present a novel tumor-targeting nano-adjuvant termed aPDL1-PLG/R848 NPs,which are composed of aPDL1 antibody,Fc-III-4C peptide linker(Fc-linker)and poly(L-glutamic acid)-grafted-R848.Under ultrasound irradiation,antigen-presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants.The strategy inhibits primary tumor growth and induces a strong antigen-specific immune memory effect to prevent tumor recurrence in vivo.This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy.
