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Self-assembled amphiphilic NIR-Ⅱ emissive nano-micelles for imaging-guided photothermal therapy of colorectal cancer

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Science China Chemistry 2024年第8期67卷 2767-2774页

作者： Axin He Fangfang Xia Da Han Qinglai Yang Weihong Tan Institute of molecular Medicine(IMM) Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Center for molecular imaging Probe Hunan Province Key Laboratory of Cancer Cellular and Molecular PathologyCancer Research InstituteHengyang Medical SchoolUniversity of South ChinaHengyang 421001China The Key Laboratory of Zhejiang Province for Aptamers and theranostics Zhejiang Cancer Hospital Hangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhou 310022China molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China

Colorectal cancer(CRC) is one of the major causes of cancer-related mortality worldwide. Most near-infrared(NIR) agents used in clinical CRC treatment are at NIR-I(700–900 nm) window, which has limitations on deep tissue, and fluorescent probes in the second NIR(1,000–1,700 nm) allow high-resolution bioimaging with deep tissue penetration. However, existing NIR-II fluorophores used in clinical are still rare. Herein, based on shielding-donor-acceptor-donor-shielding(S-D-A-D-S) scaffold, we developed an organic small-molecule fluorophore IR-BTGP with NIR-II emission for imaging-guided photothermal therapy(PTT) in CRC mice model. Amphiphilic IR-BTGP can be self-assembled into spherical nano-micelles, which presents reliable water solubility and photothermal conversion efficiency(30.2%). In vitro experiments indicate that cancer cells treated with IRBTGP were significantly killed upon 808 nm light irradiation. Furthermore, in vivo NIR-II fluorescence imaging confirms that IR-BTGP accumulates in the tumor region. Remarkably, a significant tumor inhibition rate(78.5%) was observed in tumorbearing mice when treated with IR-BTGP plus 808 nm irradiation. Therefore, this work shows that IR-BTGP holds great promise as an NIR-II fluorescence imaging-guided PTT platform for CRC in the future.

关键词： photothermal therapy(PTT) second near-infrared(NIR-Ⅱ)imaging organic molecule

The First-in-Human Whole-Body Dynamic Pharmacokinetics Study of Aptamer

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Research 2024年第1期2023卷 119-130页

作者： Ding Ding Haitao Zhao Dali Wei Qinglai Yang Cai Yang Ruowen Wang Yumei Chen Lianghua Li Shuxian An Qian Xia Gang Huang Jianjun Liu Zeyu Xiao Weihong Tan Institute of molecular Medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of Medicineand College of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Nuclear Medicine Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Center for molecular imaging Probes Cancer Research InstituteUniversity of South ChinaHengyangHunan 421001China The Key Laboratory of Zhejiang Province for Aptamers and theranostics Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangshaHunan 410082China Shanghai Key Laboratory of molecular imaging Shanghai University of Medicine and Health SciencesShanghai 201318China Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of MedicineShanghai200127China

Serving as targeting ligands,aptamers have shown promise in precision ***,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical *** bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled *** specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in *** preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human *** advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.

关键词： metabolism dosage Whole

A FRET-Based Ratiometric H_(2)S Sensor for Sensitive Optical molecular imaging in Second Near-Infrared Window

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Research 2024年第3期2023卷 671-684页

作者： Shan Lei Kejia Jiang Chenqing Zhang Wei Sun Yuantao Pan Dong Wang Peng Huang Jing Lin Marshall Laboratory of Biomedical Engineering International Cancer CenterShenzhen Key Laboratory of Tumor Visualization Molecular MedicineLaboratory of Evolutionary Theranostics(LET)School of Biomedical EngineeringShenzhen University Medical SchoolShenzhen UniversityShenzhen 518055China. Center for AIE Research College of Materials Science and EngineeringShenzhen UniversityShenzhen 518060China.

Second near-infrared(NIR-II)window optical molecular imaging kicks off a new revolution in high-quality imaging in vivo,but always suffers from the hurdles of inevitable tissue autofluorescence background and NIR-II probe ***,we prepare a Förster resonance energy transfer-based ratiometric NIR-II window hydrogen sulfide(H_(2)S)sensor through the combination of an H_(2)S-responsive NIR-II cyanine dye(acceptor,LET-1055)and an H_(2)S-inert rhodamine hybrid polymethine dye(donor,Rh930).This sensor not only exhibits high sensitivity and selectivity,but also shows rapid reaction kinetics(~20 min)and relatively low limit of detection(~96 nM)toward H_(2)S,allowing in vivo ratiometric NIR-II fluorescence imaging of orthotopic liver and colon tumors and visualization of the drug-induced hepatic H_(2)S *** findings provide the potential for advancing the feasibility of NIR-II activity-based sensing for in vivo clinical diagnosis.

关键词： H_ Infrared kinetics

The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development

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Genes & Diseases 2024年第5期11卷 252-271页

作者： Qing Ma Guang Chen Ying Li Zhenming Guo Xue Zhang NHC and CAMS Key Laboratory of molecular Probe and Targeted theranostics Harbin Medical UniversityHarbinHeilongjiang 150000China Department of Urology The Fourth Hospital of Harbin Medical UniversityHarbinHeilongjiang 150000China Department of Child and Adolescent Health School of Public HealthHarbin Medical UniversityHarbinHeilongjiang 150000China Institute for Regenerative Medicine Shanghai East HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China

Malformations of cortical development(MCD)are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental *** kinds of MCD are caused by genetic *** is the common cause of intellectual disability and intractable *** rapid advances in imaging and sequencing technologies,the diagnostic rate of MCD has been increasing,and many potential genes causing MCD have been successively ***,the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted ***,in this review,we outline important events of cortical *** we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR ***,we briefly discuss the diagnostic methods,disease models,and therapeutic strategies for *** information will facilitate further research on *** the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.

关键词： Epilepsy Gene mutation Genetics Malformations of cortical development PI3K/PTEN/AKT/mTOR pathway

Overproduction of reactive oxygen species–obligatory or not for induction of apoptosis by anticancer drugs

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Chinese Journal of Cancer Research 2016年第4期28卷 383-396页

作者： Donika Ivanova Zhivko Zhelev Ichio Aoki Rumiana Bakalova Tatsuya Higashi Medical Faculty Trakia University Institute of Biophysics & Biomedical Engineering Bulgarian Academy of Sciences Department of molecular imaging and theranostics National Institute of Radiological SciencesNational Institute for Quantum and Radiological Science and Technology Medical Faculty Sofia University

Many studies demonstrate that conventional anticancer drugs elevate intracellular level of reactive oxygen species （ROS） and alter redox-homeostasis of cancer cells. It is widely accepted that anticancer effect of these chemotherapeutics is due to induction of oxidative stress and ROS-mediated apoptosis in cancer. On the other hand, the harmful side effects of conventional anticancer chemotherapy are also due to increased production of ROS and disruption of redox-homeostasis of normal cells and tissues. This article describes the mechanisms for triggering and modulation of apoptosis through ROS-dependent and ROS^independent pathways. We try to answer the question：＂Is it possible to induce highly specific apoptosis only in cancer cells, without overproduction of ROS, as well as without harmful effects on normal cells and tissues？＂ The review also suggests a new therapeutic strategy for selective killing of cancer cells, without significant impact on viability of normal cells and tissues, by combining anticancer drugs with redox-modulators, affecting specific signaling pathways and avoiding oxidative stress.

关键词： Cancer reactive oxygen species chemotherapy ROS-independent apoptosis ROS-dependent apoptosis

Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody

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World Journal of Gastroenterology 2018年第48期24卷 5491-5504页

作者： Winn Aung Atsushi B Tsuji Aya Sugyo Hiroki Takashima Masahiro Yasunaga Yasuhiro Matsumura Tatsuya Higashi Department of molecular imaging and theranostics National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and Technology (QST-NIRS) Division of Developmental Therapeutics Exploratory Oncology Research and Clinical Trial CenterNational Cancer Center

AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer *** Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for

关键词： Pancreatic cancer Anti-tissue factor antibody Indocyanine green Photoimmunotherapy Near-infrared

Beyond Antibiotics:Photo/Sonodynamic Approaches for Bacterial theranostics

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Nano-Micro Letters 2020年第10期12卷 313-335页

作者： Xin Pang Dengfeng Li Jing Zhu Jingliang Cheng Gang Liu Henan Key Laboratory of Functional Magnetic Resonance imaging and molecular imaging Department of Magnetic Resonance ImagingThe First Affiliated Hospital of Zhengzhou University450052 ZhengzhouPeople’s Republic of China State Key Laboratory of molecular Vaccinology and molecular Diagnostics and Center for molecular imaging and Translational Medicine School of Public HealthXiamen University361102 XiamenPeople’s Republic of China Amoy Hopeful Biotechnology Co. Ltd361027 XiamenPeople’s Republic of China

Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent *** treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species(ROS),which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance *** replacing light with low-frequency ultrasonic wave to activate sensitizer,a novel ultrasounddriven treatment emerges as antimicrobial sonodynamic therapy(aSDT).Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections,especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers,and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for *** this review,we systemically outline the mechanisms,targets,and current progress of aPDT/SDT for bacterial theranostic ***,potential limitations and future perspectives are also highlighted.

关键词： Photodynamic therapy Sonodynamic therapy theranostics Multidrug resistant Reactive oxygen species

Triphenylamine-AIEgens photoactive materials for cancer theranostics

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Chinese Chemical Letters 2024年第6期35卷 86-94页

作者： Junjie Wang Yan Wang Zhengdong Li Changqiang Xie Musammir Khan Xingzhou Peng Fabiao Yu State Key Laboratory of Digital Medical Engineering School of Biomedical EngineeringHainan UniversityHaikou 570228China Key Laboratory of Biomedical Engineering of Hainan Province One Health InstituteHainan UniversityHaikou 570228China Key Laboratory of Hainan Trauma and Disaster Rescue The First Affiliated Hospital of Hainan Medical UniversityHainan Medical UniversityHaikou 571199China Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices Key Laboratory of Emergency and TraumaMinistry of EducationKey Laboratory of Hainan Functional Materials and Molecular ImagingCollege of Emergency and TraumaHainan Medical UniversityHaikou 571199China Precision Medical Center Guangyuan City Centre hospitalGuangyuan 628099China School of Natural Sciences(SNS) National University of Science and Technology(NUST)H-12Islamabad 44000Pakistan

Triphenylamine(TPA)-based aggregation-induced emission luminogens(TPA-AIEgens),a type of photoactive material utilizing the typical TPA moiety,has recently attracted increasing attention for the diagnostics and treatment of tumors due to their remarkable chemo-physical performance in optoelectronic ***-AIEgens are distinguished from other photoactive agents by their strong fluorescence,good sensitivity,high signal-to-noise ratio,resistance to photobleaching,and lack of high concentration or aggregation-caused fluoresce quenching *** this review,we summarize the current advancements and the biomedical progress of TPA-AIEgens in tumor ***,the design principles of TPAAIEgens photoactive agents as well as the advanced targeting strategies for nuclei,cell membranes,cell organelle and tumors were introduced,***,the applications of TPA-AIEgens in tumor diagnosis and therapeutic techniques were ***,the challenges and prospects of TPA-AIEgens for cancer therapy were *** given landscape of the TPA-AIEgens hereby is meaningful for the further design and utilization of the novel photoactive material,which could be beneficial for the development of clinic applications.

关键词： Triphenylamine AIEgens Targeting theranostics Phototherapy Immunotherapy

Cell-surface cascaded landing location for nanotheranostics

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Chinese Chemical Letters 2017年第9期28卷 1799-1800页

作者： En Ren Junqing Wang Gang Liu State Key Laboratory of molecular Vaccinology molecular Diagnostics Center for Molecular Imaging Translational MedicineSchool of Public Health Xiamen UniversityXiamen 361005 China

theranostics is an appealing approach in precision medicine and it is still a critical challenge to design smart strategies which can precisely accumulate the functional probes/drugs into targeted disease ***-surface cascaded landing location is an effective strategy to develop functional drug-loading platforms to explore basic physiological processes at the cellular level and to facilitate the development of nanotheranostics for disease treatment.

关键词： theranostics molecular imaging Nanomedicine Cell-surface engineering Self-assembliag