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ANTP-SMACN7 fusion peptide alone induced high linear energy transfer irradiation radiosensitization in non-small cell lung cancer cell lines

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Cancer Biology & Medicine 2022年第7期19卷 983-994页

作者： Yi Xie Bing Wang Liqing Du Yan Wang Chang Xu Hong Zhang Kaixue Wen Qiang Liu Takanori Katsube Institute of Modern Physics Chinese Academy of SciencesLanzhou 730000China Advanced Energy Science and Technology Guangdong Laboratory Huizhou 516029China National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and TechnologyChiba 263-8555Japan Institute of Radiation Medicine Chinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Shanxi Bethune Hospital Shanxi Academy of Medical ScienceTaiyuan 030031China

Objective:The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins,ANTP-SMACN7,on lung cancer cells treated with accelerated carbon and Fe particle irradiation.Methods:The ANTP-SMACN7 fusion peptide was synthesized and linked to fluorescein isothiocyanate to determine its ability to penetrate cells.A549 and NCI-H460 cells,human non-small cell lung cancer(NSCLC)cell lines,were irradiated with X-ray or high linear energy transfer(LET)irradiation with or without ANTP-SMACN7 treatment.Cellular survival,apoptosis,and protein expression were studied by colony formation assays,flow cytometry,and western blot analyses,respectively.Results:ANTP-SMACN7 fusion proteins entered the cells and promoted A549 and NCI-H460 cell high LET irradiation radiosensitization.High LET irradiation was more efficient for clonogenic cell killing and the induction of apoptosis(P<0.05).Treatment with ANTP-SMACN7 significantly reduced the A549 and NCI-H460 cell clone-forming percentages and increased apoptosis through inhibition of the X-linked inhibitor of apoptosis protein and the activation of caspase-3 and caspase-9.Conclusions:Regarding pharmaceutical radiosensitization,these findings provided a way to improve high-LET clinical radiotherapy for NSCLC patients.

关键词： Fe-particle radiation carbon-particle radiation non-small cell lung cancer cells caspase Radiosensitizer

Boosting image-guiding radiation therapy through W_(18)O_(49) nanospheres and the second near-infrared light irradiation

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Nano Research 2022年第3期15卷 2315-2323页

作者： Nannan Zheng Shouhao Zhang Lu Wang Zhilin Qi Qiang Peng Lingrui Jian Yang Bai Yue Feng Jiachen Shen Ranxu Wang Jia Jiao Wanhai Xu Shaoqin Liu School of Life Science and Technology MOE Key Laboratory of Micro-systems and Micro-structures ManufacturingHarbin Institute of TechnologyHarbin 150080China NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy Harbin Medical UniversityHarbin 150001China The First Affiliated Hospital Department of EndodonticsHarbin Medical UniversityHarbin 150080China Department of Gynecological Radiotherapy Harbin Medical University Cancer HospitalHarbin 150081China

More than 60%of cancer patients receive radiation therapy(RT)during their anticancer treatment.However,there is a huge challenge to improve the therapeutic efficacy of RT in less radioresponsive tumors and decrease damages dealt to the surrounding healthy tissues.Herein,we have reported the development of an efficacious RT treatment of relatively radio-resistant breast cancer using W_(18)O_(49)nanospheres and the second near-infrared(NIR)light irradiation.Featuring the X-ray attenuation ability and photothermal effect,together with ability to generate intracellular singlet oxygen and·OH,W_(18)O_(49)nanospheres can significantly increase radiation-induced DNA damage and decrease the mitochondrial membrane potential of cancer cells during RT,causing in nearby three-times improvement in inhibiting the proliferation of 4T1 cells.The in vivo evaluations verify that a rather effective therapeutic outcome is achieved by treatment of 4T1 tumor xenograft with NIR-enhanced RT using W_(18)O_(49)nanospheres.Moreover,the X-ray attenuation ability and the strong near-infrared absorption of W_(18)O_(49)nanospheres have enabled highly resolved in vivo computer tomography(CT)/photoacoustic(PA)imaging.This work presents an“all-in-one”synergistic platform to improve the therapeutic efficacy of RT in less radioresponsive tumors,therefore opening a new door for multimodal cancer therapy.

关键词： W_(18)O_(49) tumor metastasis Radiosensitizer phototherapy singlet oxygen

Complete ablation of tumors using synchronous chemoradiation with bimetallic theranostic nanoparticles

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Bioactive Materials 2022年第1期7卷 74-84页

作者： Hamed Nosrati Elahe Attari Fatemeh Abhari Murat Barsbay Mohammadreza Ghaffarlou Navid Mousazadeh Rasoul Vaezi Taras Kavetskyy Hamed Rezaeejam Thomas J.Webster Behrooz Johari Hossein Danafar Zanjan Pharmaceutical Biotechnology Research Center Zanjan University of Medical SciencesZanjanIran Joint Ukraine-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems DrohobychUkraineBakuAzerbaijan Department of Radiology School of Paramedical SciencesZanjan University of Medical SciencesZanjan45139-56184Iran Hacettepe University Department of ChemistryBeytepeAnkara06800Turkey Department of Medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjan45139-56184Iran Department of Pharmaceutical Nanotechnology School of PharmacyZanjan University of Medical SciencesZanjanIran Department of Surface Engineering The John Paul II Catholic University of Lublin20-950LublinPoland Drohobych Ivan Franko State Pedagogical University 82100DrohobychUkraine Department of Chemical Engineering Northeastern University360 Huntington AvenueBostonMA02115United States

Synchronous chemotherapy and radiotherapy,termed chemoradiation therapy,is now an important standard regime for synergistic cancer treatment.For such treatment,nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better Radiosensitizers for localized radiotherapy.Herein,we designed a Schottky-type theranostic heterostructure,Bi_(2)S_(3)-Au,with deep level defects(DLDs)in Bi_(2)S_(3) as a nano-Radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation.Methotrexate(MTX)was conjugated onto the Bi_(2)S_(3)-Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior.The designed hybrid system also contained curcumin(CUR),which cannot only serve as a nutritional supplement for chemotherapy,but also can play an important role in the radioprotection of normal cells.Impressively,this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation,completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications.

关键词： Combination therapy Radiosensitizer Semiconductor Heterojunction Radioprotector

High-dimensional zinc porphyrin nanoframeworks as efficient Radiosensitizers for cervical cancer

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Chinese Chemical Letters 2023年第7期34卷 182-185页

作者： Fei Cai Kun Ye Mingkai Chen Yuan Tian Peicong Chen Hao Lin Tianfeng Chen Li Ma Department of Chemistry Jinan UniversityGuangzhou 510632China Department of Orthopedics Affiliated Hospital of Guangdong Medical UniversityZhanjiang 524001China

Radiotherapy is widely used clinically, but the toxic and side effects of nonselective killing of high-energy radiation limit its application. Finding biocompatible materials to assemble radiotherapy sensitizers and studying their sensitization patterns are of great significance for the clinical application. Here, biocompatible zinc porphyrin was chosen as sub-unit to construct various dimensional coordination frameworks. By employing top-down approach, suitable nanoframeworks with various dimensional zinc porphyrin were synthesized as Radiosensitizers. The experimental data showed that high-dimensional zinc porphyrin nanoframeworks exhibit higher X-ray response performance.

关键词： Zinc porphyrin frameworks Nanoframeworks Radiosensitizer Apoptosis

Selectively enhancing radiosensitivity of cancer cells via in situ enzyme-instructed peptide self-assembly

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2374-2383页

作者： Yang Gao Jie Gao Ganen Mu Yumin Zhang Fan Huang Wenxue Zhang Chunhua Ren Cuihong Yang Jianfeng Liu Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Radiation Oncology Department Tianjin Medical University General HospitalTianjin 300052China

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity.For the first time,we used the in situ enzyme-instructed self-assembly(EISA)of a peptide derivative(Nap-GDFDFpYSV)to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase(ALP)expression to ionizing radiation(IR).Compared with the in vitro pre-assembled control formed by the same molecule,assemblies formed by in situ EISA in cells greatly sensitized the ALPhigh-expressing cancer cells to y-rays,with a remarkable sensitizer enhancement ratio.Our results indicated that the enhancement was a result of fixing DNA damage,arresting cell cycles and inducing cell apoptosis.Interestingly,in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells,while the assemblies formed via in situ EISA scattered in the cell cytosol.The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors.We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP.This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor Radiosensitizers.

关键词： In situ enzyme-instructed self-assembly(EISA) Pre-assembly Alkaline phosphatase(ALP) Peptide Cancer radiotherapy Nanofiber Histone deacetylases inhibitor(HDACI) Radiosensitizer

Dual-targeting and microenvironment-responsive micelles as a gene delivery system to improve the sensitivity of glioma to radiotherapy

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Acta Pharmaceutica Sinica B 2019年第2期9卷 381-396页

作者： Xiuxiu Jiao Yuan Yu Jianxia Meng Mei He Charles Jian Zhang Wenqian Geng Baoyue Ding Zhuo Wang Xueying Ding Department of Pharmaceutics Shanghai General Hospital Shanghai Jiao Tong University of Medicine Department of Pharmaceutical Sciences School of Pharmacy Second Military Medical University Department of Pharmacy Changhai Hospital Second Military Medical University Department of Pharmaceutical Sciences College of Pharmacy Western University of Health Sciences Department of Pharmaceutics College of Medicine Jiaxing University

Dbait is a small double-stranded DNA molecule that has been utilized as a Radiosensitizer to enhance the sensitivity of glioma to radiotherapy(RT). However, there is no effective drug delivery system to effectively overcome the blood–brain barrier(BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles(ch-Kn(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1(LRP1) that is overexpressed on brain capillary endothelial cells(BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2(MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-Kn(s-s)R8-An micelles maintained a reasonable size(80–160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration(CMC) with positive surface charge, ranging from 15 to40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency in vitro, improved uptake in glioma cells and good biocompatibility in vitro and in vivo. In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells in vitro. Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.

关键词： Glioma-targeting Cell-penetrating peptides Microenvironment-responsive micelles Gene delivery Radiosensitizer

Identification of anticancer drugs to radiosensitise BRAF-wild-type and mutant colorectal cancer

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Cancer Biology & Medicine 2019年第2期16卷 234-246页

作者： Rebecca Carter Azadeh Cheraghchi-Bashi Adam Westhorpe Sheng Yu Yasmin Shanneik Elena Seraia Djamila Ouaret Yasuhiro Inoue Catherine Koch Jenny Wilding Daniel Ebner Anderson J. Ryan Francesca M. Buffa Ricky A. Sharma NIHR University College London Hospitals Biomedical Research Centre/ UCL Cancer Institute University College London London WC1E 6DD UK NIHR Oxford Biomedical Research Centre Department of Oncology University of Oxford Oxford 0X1 2JD UK Computational Biology and Integrative Genomics University of Oxford Oxford 0X1 2JD UK NDM Research Building Nuffield Department of Medicine University of Oxford Oxford 0X1 2JD UK Weatherall Institute of Molecular Medicine John Radcliffe Hospital University of Oxford Oxford 0X1 2JD UK Mie University Graduate School of Medicine Department of Gastrointestinal and Pediatric Surgery Division of Reparative Medicine Institute of Life Sciences Edobashi 2-174 Tsu Japan Departme nt of Biology Massachusetts In stitute of Tech no logy Cambridge Massachusetts 02142 USA Target Discovery Institute National Phenotypic Screening Centre Nuffield Department of Medicine University of OxfordOxford 0X1 2JD UK CRUK & MRC Oxford Institute for Radiation Oncology University of Oxford Oxford 0X1 2JD UK

Objective: Patients with BRAF-mutant colorectal cancer(CRC) have a poor prognosis. Molecular status is not currently used to select which drug to use in combination with radiotherapy. Our aim was to identify drugs that radiosensitise CRC cells with known BRAF status.Methods: We screened 298 oncological drugs with and without ionising radiation in colorectal cancer cells isogenic for BRAF. Hits from rank product analysis were validated in a 16-cell line panel of human CRC cell lines, using clonogenic survival assays and xenograft models in vivo.Results: Most consistently identified hits were drugs targeting cell growth/proliferation or DNA damage repair. The most effective class of drugs that radiosensitised wild-type and mutant cell lines was PARP inhibitors. In clonogenic survival assays, talazoparib produced a radiation enhancement ratio of 1.9 in DLD1(BRAF-wildtype) cells and 1.8 in RKO(BRAF V600 E) cells. In DLD1 xenografts, talazoparib significantly increased the inhibitory effect of radiation on tumour growth(P ≤ 0.01).Conclusions: Our method for screening large drug libraries for radiosensitisation has identified PARP inhibitors as promising radiosensitisers of colorectal cancer cells with wild-type and mutant BRAF backgrounds.

关键词： Radiosensitizer colorectal cancer PARP inhibitor radiotherapy

Substituent-regulated highly X-ray sensitive Os(Ⅵ)nitrido complex for low-toxicity radiotherapy

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Chinese Chemical Letters 2021年第1期32卷 158-161页

作者： Mingkai Chen Xiaoting Huang Jie Lai Li Ma Tianfeng Chen Department of Chemistry Jinan UniversityGuangzhou 510632China

A high efficiency and low toxicity Radiosensitizer,OsN(PhenOH)Cl_3,was designed and synthesized through substituent regulation.To the best of our knowledge,this is the first osmium-based coordination complex Radiosensitizer.The experimental results shown that this Radiosensitizer induced G2/M cell cycle arrest mainly through induction of intracellular ROS overproduction.

关键词： Os(Ⅵ)nitrido Complex Radiotherapy Radiosensitizer G2/M cell cycle arrest

Surface-ligand effect on radiosensitization of ultrasmall luminescent gold nanoparticles

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Journal of Innovative Optical Health Sciences 2016年第4期9卷 66-73页

作者： Xingya Jiang Bujie Du Mengxiao Yu Xun Jia Jie Zheng Department of Chemistry and Biochemistry The University of Texas at Dallas 800 W.Campbell Rd. RichardsonTX 75080USA Department of Radiation Oncology The University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard DallasTX 75390USA

Gold nanoparticles(AuNPs)could serve as pot ential radiother apy sensitizers because of their exceptional biocompatibility and high.Z material nature;however,since in vitro and in vivo behaviors of AuNPs are determined not only by their particle size but also by their surface chemistries,whether surface ligands can affect their radiosensitization has seldom been investi-gated in the radiosensitization of AuNPs.By conducting head-to-head comparison on radio-sensitization of two kinds of ultrasmall(~2 nm)near-infrared(NIR)emitting AuNPs that are coated with zwitterionic glutathione and neutr al polyethylene glyol(PEG)ligands,respectively,we found that zwitterionic glut athione coated AuNPs(GS-AuNPs)can reduce survival rates of MCF-7 cells under irr adiation of clinically used megavoltage photon beam at low dosage of~2.25 Gy.On the other hand,PEG-AuNPs can serve as a radiation-protecting agent and enabled MCF-7 cells more resistant to the irradiation,clearly indicating the key role of surface cheistry in radiosensitization of AuNPs.More detailed studies suggested that such difference was inde-pendent of cellular uptake and its eficiency,but might be related to the ligand-induced difference in photoelectron generation and/or inter actions between AuNPs and X-ray triggered reactive oxygen species(ROS).

关键词： Gold nanoparticles surface-ligand cell uptake Radiosensitizer radiation-protecting