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Size-transformable nanoparticles with sequentially triggered drug release and enhanced penetration for anticancer therapy

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Nano Research 2023年第8期16卷 11186-11196页

作者： Yulin Li Liudi Wang Guoqiang Zhong Guoying Wang Yanzhao Zhu Jian Li Lan Xiao Yanhui Chu Yan Wu Kaichun Li Jie Gao Engineering Research Centre for Biomedical Materials of Ministry of Education The Key Laboratory for Ultrafine Materials of Ministry of EducationFrontiers Science Center for Materiobiology and Dynamic ChemistrySchool of Material Science and EngineeringEast China University of Science and TechnologyShanghai 200237China Department of Oncology Shanghai Fourth People’s Hospital School of MedicineTongji UniversityShanghai 200434China Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghai 200433China College of Life Sciences Mudanjiang Medical University Mudanjiang 157011China Wenzhou Institute of Shanghai University Wenzhou 325000China Centre for Biomedical Technologies Queensland University of TechnologyBrisbaneQLD 4059Australia

There are several limitations to the application of nanoparticles in the treatment of cancer,including their low drug loading,poor colloidal stability,insufficient tumor penetration,and uncontrolled release of the ***,gelatin/laponite(LP)/doxorubicin(GLD)nanoparticles are developed by crosslinking LP with gelatin for doxorubicin *** shows high doxorubicin encapsulation efficacy(99%)and strong colloidal stability,as seen from the unchanged size over the past 21 days and reduced protein absorption by 48-fold compared with unmodified laponite/doxorubicin *** gelatin from 115 nm GLD reaches the tumor site,matrix metallopeptidase-2(MMP-2)from the tumor environment breaks it down to release smaller 40 nm LP nanoparticles for effective tumor cell *** demonstrated by superior penetration in both in vitro three-dimensional(3D)tumor spheroids(138-fold increase compared to the free drug)and in vivo tumor *** intracellular low pH and MMP-2 further cause doxorubicin release after endocytosis by tumor cells,leading to a higher inhibitory potential against cancer *** improved anticancer effectiveness and strong in vivo biocompatibility of GLD have been confirmed using a mouse tumor-bearing ***-2/pH sequentially triggered anticancer drug delivery is made possible by the logical design of tumor-penetrating GLD,offering a useful method for anticancer therapy.

关键词： sequentially triggered drug release size-transformable nanoparticles tumor penetration anticancer therapy drug delivery

Remotely Activated Nanoparticles for anticancer therapy

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Nano-Micro Letters 2021年第1期13卷 174-207页

作者： Luisa Racca Valentina Cauda Department of Applied Science and Technology Politecnico di TorinoC.so Duca degli Abruzzi 2410129 TurinItaly

Cancer has nowadays become one of the leading causes of death *** anticancer approaches are associated with different ***,innovative methodologies are being investigated,and several researchers propose the use of remotely activated nanoparticles to trigger cancer cell *** idea is to conjugate two different components,i.e.,an external physical input and *** are given in a harmless dose that once combined together act synergistically to therapeutically treat the cell or tissue of interest,thus also limiting the negative outcomes for the surrounding *** both the properties of the nanomaterial and the involved triggering stimulus,it is possible furthermore to achieve not only a therapeutic effect,but also a powerful platform for imaging at the same time,obtaining a nano-theranostic *** the present review,we highlight the role of nanoparticles as therapeutic or theranostic tools,thus excluding the cases where a molecular drug is *** thus present many examples where the highly cytotoxic power only derives from the active interaction between different physical inputs and *** perform a special focus on mechanical waves responding nanoparticles,in which remotely activated nanoparticles directly become therapeutic agents without the need of the administration of chemotherapeutics or sonosensitizing drugs.

关键词： anticancer therapy Remotely activated nanomedicine Stimuli-responsive nanoparticles Physical stimulation Radiofrequency Nanoparticle-assisted ultrasound Hyperthermia

Targeting necroptosis in anticancer therapy:mechanisms and modulators

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Acta Pharmaceutica Sinica B 2020年第9期10卷 1601-1618页

作者： Ying Wu Guoqiang Dong Chunquan Sheng School of Pharmacy Second Military Medical UniversityShanghai 200433China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China

Necroptosis,a genetically programmed form of necrotic cell death,serves as an important pathway in human *** a critical cell-killing mechanism,necroptosis is associated with cancer progression,metastasis,and *** necroptosis pathway by small molecule modulators is emerging as an effective approach in cancer therapy,which has the advantage to bypass the apoptosis-resistance and maintain antitumor ***,a better understanding of the mechanism of necroptosis and necroptosis modulators is necessary to develop novel strategies for cancer *** review will summarize recent progress of the mechanisms and detecting methods of *** particular,the relationship between necroptosis and cancer therapy and medicinal chemistry of necroptosis modulators will be focused on.

关键词： Cell death Necroptosis Inducers Inhibitors anticancer therapy

Sex-determining Region of Y Chromosome-related High-mobility-group Box 2 in Malignant Tumors： Current Opinions and anticancer therapy

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Chinese Medical Journal 2015年第3期128卷 384-389页

作者： Shi-Guang Cao Zong-Juan Ming Yu-Ping Zhang Shuan-Ying Yang Department of Respiratory Medicine Second Affiliated HospitaL Xi'an Jiaotong University Xi'an Shaanxi 710004 China

Objective： To gain insight into the mechanism by which sex-determining region of Y chromosome （SRY）-related high-mobility-group box 2 （SOX2） involved in carcinogenesis and cancer stem cells （CSCs）. Data Sources： The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were ＂SOX2,＂＂cancer,＂＂tumor＂ or ＂CSCs.＂ Study Selection： Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed. Results： SOX2, a transcription factor that is the key in maintaining pluripotent properties of stem cells, is a member of SRV-related high-mobility group domain proteins. SOX2 participates in many biological processes, such as modulation of cell proliferation, regulation of cell death signaling, cell apoptosis, and most importantly, tumor formation and development. Although SOX2 has been implicated in the biology of various tumors and CSCs, the findings are highly controversial, and information regarding the underlying mechanism remains limited. Moreover, the mechanism by which SOX2 involved in carcinogenesis and tumor progression is rather unclear yet. Conclusions： Here, we review the important biological functions of SOX2 in different tumors and CSCs, and the function of SOX2 signaling in the pathobiology ofneoplasia, such as Wnt/β-catenin signaling pathway, Hippo signaling pathway, Survivin signaling pathway, P13K/Akt signaling pathway, and so on. Targeting towards SOX2 may be an effective therapeutic strategy for cancer therapy.

关键词： anticancer therapy Cancer Cancer Stem Cell Signaling Sex-determining Region of Y Chromosome-related High-mobility-group Box 2

Cardiovascular disease burden in patients with urological cancers:The new discipline of uro-cardio-oncology

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Cancer Innovation 2024年第2期3卷 28-44页

作者： Yi Zheng Ying Liu Ziliang Chen Yunpeng Zhang Zuo Qi Ning Wu Zhiqiang Zhao Gary Tse Yong Wang Hailong Hu Yuanjie Niu Tong Liu Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of CardiologySecond Hospital of Tianjin Medical UniversityTianjinChina School of Nursing and Health Studies Hong Kong Metropolitan UniversityHong KongChina

Cancer remains a major cause of mortality worldwide,and urological cancers are the most common cancers among *** therapeutic agents have been used to treat urological cancer,leading to improved survival for ***,this has been accompanied by an increase in the frequency of survivors with cardiovascular complications caused by anticancer medica***,we propose the novel discipline of uro-cardio-oncology,an evolving subspecialty focused on the complex interactions between cardiovascular disease and urological *** this comprehensive review,we discuss the various cardiovascular toxicities induced by different classes of antineoplastic agents used to treat urological cancers,including androgen deprivation therapy,vascular endothelial growth factor receptor tyrosine kinase inhibitors,immune checkpoint inhibitors,and *** addition,we discuss possible mechanisms underlying the cardiovascular toxicity associated with anticancer therapy and outline strategies for the surveillance,diagnosis,and effective management of cardiovascular compli***,we provide an analysis of future perspectives in this emerging specialty,identifying areas in need of further research.

关键词： anticancer therapy cardiovascular toxicity mechanism multidisciplinary management urological cancer

Polyoxometalates based nanocomposites for bioapplications

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Rare Metals 2023年第11期42卷 3570-3600页

作者： Yao Cheng Ke-Jie Qin De-Jin Zang School of Pharmacy and Pharmaceutical Sciences&Institute of Materia Medica National Key Laboratory of Advanced Drug Delivery and SystemShandong First Medical University&Shandong Academy of Medical SciencesNHC Key Laboratory of Biotechnology Drugs(Shandong Academy of Medical Sciences)Key Lab for Rare&Uncommon Diseases of Shandong ProvinceJinan250117China

Health care and medical care have always been dominant topics in human *** field of precision medicine,iatrotechnics revolution and timely on-demand detection have continued to evolve in response to increasing demands from the ***,the emergence of innovative materials and their applications offer promising prospects for advancing global ***(POMs)are negatively-charged molecular metal oxides with well-defined structures,beautiful geometries and nanoscale *** to their vast diversity in composition,structure,nuclearity and charge,they constitute a significant subcategory of inorganic clusters that contain bridging oxygen atoms between two or more metal ***,POMs based nanocomposites have been widely applied in the field of disease diagnosis,anticancer therapy and antibacterial therapy as new generation bioactive *** this review,the recent advances of POMs based nanocomposites in bioapplications are summarized and the future perspectives are discussed.

关键词： Polyoxometalates(POMs) Disease diagnosis anticancer therapy Antibacterial therapy Biological imaging

Recent advances in organic and polymeric carriers for local tumor chemo-immunotherapy

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Science China(Technological Sciences) 2022年第5期65卷 1011-1028页

作者： BAI YiTing WANG TianRan ZHANG SongLing CHEN XueSi HE ChaoLiang Department of Obstetrics and Gynecology The First Hospital of Jilin UniversityChangchun130021China CAS Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China

Combination therapy involves the simultaneous administration of compounds with varying mechanisms of action that can improve the efficacy of antitumor therapy and reduce *** most widely used combination regimen is chemotherapy combined with focused *** is implemented to induce the apoptosis of tumor cells and can activate immune responses,improving the clearance rate of primary lesions and maintaining the resistance to postoperative tumor recurrence and *** in micro/nanotechnology,nanomedicine and biomaterials have contributed to the development of enhanced local drug co-delivery systems for cancer treatment,improving tumor targeting and ameliorating severe systemic *** materials can achieve the local long-term controllable release of multiple drugs,which not only avoids rapid drug diffusion from the pathological site,but can achieve synergistic effects at lower drug *** carriers display excellent biocompatibility and biodegradability;especially,some of them also have anti-tumor *** aim of this article was to review recent progress in the use of organic and polymeric materials for local tumor chemo-immunotherapy,which can be used as carriers for chemotherapeutic drugs,immune adjuvants and genes,including amphiphilic nanoparticles,nanocapsules,nano-disks,nano-polyplex particles,hydrogels and implantable materials.

关键词： chemo-immunotherapy nanocarrier hydrogel anticancer therapy biomedical polymer

Nanomedicine-Leveraged Intratumoral Coordination and Redox Reactions of Dopamine for Tumor-Specific Chemotherapy

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CCS Chemistry 2022年第5期4卷 1499-1509页

作者： Bowen Yang Yuedong Guo Yuemei Wang Jiacai Yang Heliang Yao Jianlin Shi State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai 200050 Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049

Great efforts have been made in investigating the neurotoxicity of dopamine(DA)in the presence of manganous *** contrast,here,we probe the possibility of DA-based cancer chemotherapy by leveraging intratumoral redox reactions of DA for producing cytotoxic species in *** this purpose,we have constructed a Mn-engineered,DA-loaded *** on the unique size effect of the nanocarrier,this nanomedicine will not enter the central nervous system but can effectively accumulate in the tumor region,after which the nanocarrier can degrade to release Mn^(2+)and DA in response to the mild acidic intracelluar microenvironment of cancer *** can chelate Mn^(2+)to form a binary coordination complex,where the strong metal-ligand interaction significantly promotes electron delocalization and elevates the reducibility of Mn center,favoring two sequential one-electron oxygen reduction reactions forming H_(2)O_(2),which can be further converted into highly oxidizing ·OH under the cocatalysis by Mn^(2+)and intracellular Fe^(2+).Additionally,as a twoelectron oxidation product of DA ligand,DA-oquinone is potent in exhausting cellular sulfhydryl and depleting reduced glutathione,inhibiting the intrinsic antioxidative mechanism of cancer cells,finally triggering severe oxidative damages in a synergistic *** is expected that such a strategy of nanotechnology-mediated metal-ligand coordination and subsequent nontoxicity-to-toxicity transition of DA in tumor may provide a promising prospect for future chemotherapy design.

关键词： dopamine mesoporous silica nanoparticle manganese catalysis redox reactions anticancer therapy

The current status of anti-GPCR drugs against different cancers

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Journal of Pharmaceutical Analysis 2020年第6期10卷 517-521页

作者： Sana Usman Maria Khawer Shazia Rafique Zara Naz Komal Saleem Centre for Applied Molecular Biology 87-West Canal Bank Road Thokar Niaz BaigUniversity of the PunjabLahorePakistan Centre of Excellence in Molecular Biology University of the PunjabLahorePakistan

G protein coupled receptors(GPCRs)have emerged as the most potential target for a number of drug discovery programs ranging from control of blood pressure,diabetes,cure for genetic diseases to treatment of cancer.A panel of different ligands including hormones,peptides,ions and small molecules is responsible for activation of these *** genetics has identified key GPCRs,whose mutations or altered expressions are linked with *** this review,we discussed recent advances regarding the involvement of GPCRs in the development of cancers and approaches to manipulating the mechanism behind GPCRs involved tumor growth and metastasis to treat different types of human *** review provides an insight into the current scenario of GPCR-targeted therapy,progress to date and the challenges in the development of anticancer drugs.

关键词： GPCRs anticancer therapy Pancreatic cancer Colon cancer CLL Prostate cancer Melanoma