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Recent Progress in Endoplasmic Reticulum-Targetable Small-Molecule Probes for Fluorescence Sensing and phototherapy

Journal of Analysis and Testing 2023年第3期7卷 304-324页

作者： Jing Chen Huihong Liu Wenzhi Xie Maoxin Gu Guojiang Mao Sheng Yang Hunan Provincial Key Laboratory of Cytochemistry School of Chemistry and Chemical EngineeringChangsha University of Science and TechnologyChangsha 410114China Laboratory of Chemical Biology and Traditional Chinese Medicine Research(Ministry of Education) College of Chemistry and Chemical EngineeringHunan Normal UniversityChangsha 410081China Henan Key Laboratory of Organic Functional Molecule and Drug Innovation Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine ChemicalsKey Laboratory of Green Chemical Media and ReactionsMinistry of EducationSchool of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiang 453007China

The endoplasmic reticulum(ER)is the most widespread organelle within eukaryotic cells,performing various essential functions such as protein synthesis,post-translational modifications,and lipid metabolism.Abnormal fluctuations of biologically active species and microenvironments in the ER can disrupt homeostasis and eventually lead to ER stress,which is closely linked to the occurrence and progression of many human diseases.Therefore,the ER has been regarded as an important analytical object as well as a promising therapeutic target in both bio sensing and biomedicine.Recently,there has been a growing interest in developing photon-excited molecular tools to uncover the physio pathological roles of ER and treat ERrelated disorders.This review presents a comprehensive summary of recent advances in ER-targeted small-molecule probes and their applications for fluorescent sensing and phototherapy,mainly focusing on targeting strategies and probe design principles.Last,we discuss the challenges involved with ER-targeted probes and highlight potential prospects in this field.

关键词： Endoplasmic reticulum Organelle-targetable fl uorescent probe Subcellular analysis Endoplasmic reticulum stress phototherapy

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Emerging nanoformulation strategies for phytocompounds and applications from drug delivery to phototherapy to imaging

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Bioactive Materials 2022年第8期7卷 182-205页

作者： Hwa Seung Han Song Yi Koo Ki Young Choi Natural Product Informatics Research Center Korea Institute of Science and Technology(KIST)Gangneung25451Republic of Korea Division of Bio-Medical Science and Technology KIST SchoolUniversity of Science and Technology(UST)Seoul02792Republic of Korea

Over thousands of years,natural bioactive compounds derived from plants(bioactive phytocompounds,BPCs)have been used worldwide to address human health issues.Today,they are a significant resource for drug discovery in the development of modern medicines.Although many BPCs have promising biological activities,most of them cannot be effectively utilized in drugs for therapeutic applications because of their inherent limitations of low solubility,structural instability,short half-life,poor bioavailability,and non-specific distribution to organs.Researchers have utilized emerging nanoformulation(NF)technologies to overcome these limitations as they have demonstrated great potential to improve the solubility,stability,and pharmacokinetic and pharmacodynamic characteristics of BPCs.This review exemplifies NF strategies for resolving the issues associated with BPCs and summarizes recent advances in their preclinical and clinical applications for imaging and therapy.This review also highlights how innovative NF technologies play a leading role in next-generation BPC-based drug development for extended therapeutic applications.Finally,this review discusses the opportunities to take BPCs with meaningful clinical impact from bench to bedside and extend the patent life of BPC-based medicines with new formulations or application to new adjacent diseases beyond the primary drug indications.

关键词： Natural products Phytocompound Nanoformulation Drug delivery phototherapy

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Biomimetic biomineralization nanoplatform-mediated differentiation therapy and phototherapy for cancer stem cell inhibition and antitumor immunity activation

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Asian Journal of Pharmaceutical Sciences 2023年第5期18卷 164-184页

作者： Shan Gao Meng Liu Dongzhu Liu Xinru Kong Yuelin Fang Yingying Li Hang Wu Jianbo Ji Xiaoye Yang Guangxi Zhai Department of Pharmaceutics Key Laboratory of Chemical Biology(Ministry of Education)NMPA Key Laboratory for Technology Research and Evaluation of Drug ProductsSchool of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinanShandong250012China

Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis.Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy.In this work,we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid(ATRA)via biomineralization.This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters,which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration.With the help of CSC differentiation induced by ATRA,IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner.Furthermore,ATRA can boost immunogenic cell death induced by phototherapy,thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells.Taken together,this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation,improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.

关键词： Cancer stem cells Differentiation therapy phototherapy Biomineralization Immunogenic cell death

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Black TiO_(2) nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis

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Bioactive Materials 2022年第11期7卷 18-28页

作者： Ting Dai Wenming He Shuangshuang Tu Jinru Han Bo Yuan Chenyang Yao Wenzhi Ren Aiguo Wu Department of Cardiology The Affiliated Hospital of Medical SchoolNingbo University247 Renmin RoadJiangbei DistrictNingboZhejiang Province315020China Cixi Institute of Biomedical Engineering International Cooperation Base of Biomedical Materials Technology and ApplicationCAS Key Laboratory of Magnetic Materials and Devices&Zhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of Sciences1219 ZhongGuan West RoadNingbo315201China University of Chinese Academy of Sciences No.1 Yanqihu East RoadHuairou DistrictBeijing101408China Advanced Energy Science and Technology Guangdong Laboratory Huizhou516000China

Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild pho-totherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photo-thermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO_(2) nanoparticles. The results showed that when temperatures below 45 ◦C, PTT alone and PTT +PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO_(2) nanoprobes could allow safer and more effective phototherapy of atherosclerosis.

关键词： Atherosclerosis Black TiO_(2)nanoparticles phototherapy Cholesterol homeostasis

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Emerging Designs of Aggregation-Induced Emission Agents for Enhanced phototherapy Applications

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CCS Chemistry 2022年第2期4卷 401-419页

作者： Rui Qu Xu Zhen Xiqun Jiang MOE Key Laboratory of High Performance Polymer Materials and Technology Department of Polymer Science&EngineeringCollege of Chemistry&Chemical EngineeringNanjing UniversityNanjing 210093

phototherapy,including photodynamic therapy(PDT)and photothermal therapy(PTT),that employs phototherapeutic agents to generate cytotoxic reactive oxygen species(ROS)or hyperthermia,is a promising approach for disease therapy.However,conventional organic phototherapeutic agents suffer poor photostability and aggregation-caused quenching(ACQ)in the aggregate state,restricting their therapeutic efficacy.Aggregation-induced emission(AIE)agents can solve these issues with strong emission in the aggregate state and reverse designation to generate heat.This review summarizes the recent advances in the development of AIE phototherapy agents for enhanced PDT and PTT performances in biomedical applications.First,design strategies of AIE agents that adjust the intersystem crossing process or intramolecular charge transfer to boost ROS generation or regulate ROS types are discussed.The AIE agents with ROS generation ability for biomedical applications including antitumor and antibacterial performances are then introduced.Next,designs and examples of AIE agents that enhance PTT performances through molecular motions are described.Finally,the current challenges and perspectives of AIE agents in the phototherapy field are discussed.

关键词： aggregation-induced emission structural designing phototherapy photodynamic therapy photothermal therapy

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Immune modulations of the tumor microenvironment in response to phototherapy

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Journal of Innovative Optical Health Sciences 2023年第3期16卷 132-155页

作者： Trisha I.Valerio Coline L.Furrer Negar Sadeghipour Sophia-Joy X.Patrock Sayre A.Tillery Ashley R.Hoover Kaili Liu Wei R.Chen Stephenson School of Biomedical Engineering University of Oklahoma NormanOklahoma 73019USA School of Electrical and Computer Engineering University of Oklahoma NormanOklahoma 73019USA

The tumor microenvironment(TME)promotes pro-tumor and anti-infammatory metabolismsand suppresses the host immune system.It prevents immune cells from fighting against cancereffectively,resulting in limited efficacy of many current cancer treatment modalities.Differenttherapies aim to overcome the immunosuppressive TME by combining various approaches tosynergize their effects for enhanced antitumor activity and augmented stimulation of the im-mune system.Immunotherapy has become a major therapeutic strategy because it unleashes thepower of the immune system by activating,enhancing,and directing immune responses to pre-vent,control,and eliminate cancer.phototherapy uses light iradiation to induce tumor celldeath through photothermal,photochemical,and photo-immunological interactions.Photo-therapy induces tumor immunogenic cell death,which is a precursor and enhancer for anti-tumorimmunity.However,phototherapy alone has limited effects on long-term and systemic anti-tumor immune responses.phototherapy can be combined with immunotherapy to improve thetumoricidal effect by killing target tumor cells,enhancing immune cell infiltration in tumors,andrewiring pathways in the TME from antinfammatory to pro-inflammatory.phototherapy-enhanced immunotherapy triggers effective cooperation bet ween innate and adaptive immunities,specifically targeting the tumor cells,whether they are localized or distant.Herein,the successes and limitations of phototherapy combined with other cancer treatmentmodalities will be discussed.Specifically,we will review the symergistic effects of phototherapy combined with different cancer therapies on tumor elimination and remodeling of the immuno-suppressive TME.Overll,phototherapy,in combination with other therapeutic modalities,canestablish anti-tumor pro-infammatory phenotypes in activated tumor-infiltrating T cells andB cells and activate systemic anti-tumor immune responses.

关键词： phototherapy immunotherapy tumor microenvironment tumor-infiltrating lymphocytes phototherapy-induced tumor immunogenic cell death translational combination therapies

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Nb2C MXene-Functionalized Scaffolds Enables Osteosarcoma phototherapy and Angiogenesis/Osteogenesis of Bone Defects

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Nano-Micro Letters 2021年第2期13卷 162-179页

作者： Junhui Yin Shanshan Pan Xiang Guo Youshui Gao Daoyu Zhu Qianhao Yang Junjie Gao Changqing Zhang Yu Chen Institute of Microsurgery On Extremities Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233People’s Republic of China School of Life Sciences Shanghai UniversityShanghai 200444People’s Republic of China State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai 200050People’s Republic of China Department of Orthopaedic Surgery Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233People’s Republic of China Department of Orthopedics The Second Affiliated HospitalThe Navy Medical UniversityShanghai 200003People’s Republic of China

Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor,but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site.In this work,we report a rational integration of photonic-responsive two-dimensional(2D)ultrathin niobium carbide(Nb2C)MXene nanosheets(NSs)into the 3D-printed bone-mimetic scaffolds(NBGS)for osteosarcoma treatment.The integrated 2D Nb2C-MXene NSs feature specific photonic response in the second near-infrared(NIR-II)biowindow with high tissue-penetrating depth,making it highly efficient in killing bone cancer cells.Importantly,Nb-based species released by the biodegradation of Nb2C MXene can obviously promote the neogenesis and migration of blood vessels in the defect site,which can transport more oxygen,vitamins and energy around the bone defect for the reparative process,and gather more immune cells around the defect site to accelerate the degradation of NBGS.The degradation of NBGS provides sufficient space for the bone remodeling.Besides,calcium and phosphate released during the degradation of the scaffold can promote the mineralization of new bone tissue.The intrinsic multifunctionality of killing bone tumor cell and promoting angiogenesis and bone regeneration makes the engineered Nb2C MXeneintegrated composite scaffolds a distinctive implanting biomaterial on the efficient treatment of bone tumor.

关键词： Nb2C MXene 3D printing phototherapy Osteosarcoma Vascularization

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phototherapy FOR MILD TO MODERATE ACNE VULGARIS WITH PORTABLE BLUE AND RED LED

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Journal of Innovative Optical Health Sciences 2011年第1期4卷 45-52页

作者： GUANGDA LIU CHANGE PAN KAI LI YUAN TAN XUNBIN WEI Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China Shanghai Medical School Fudan UniversityShanghai 200032China School of Life Sciences Fudan UniversityShanghai 200032China Department of Chemistry Fudan UniversityShanghai 200032China Cancer Hospital Fudan UniversityShanghai 200032China

In this paper,we studied portable blue and red light-emitting-diode(LED)light sources in phototherapy for mild to moderate acne vulgaris to evaluate the efficacy and tolerance of patients.Patients,randomly divided into blue and red groups,received either blue or red LED phototherapy twice a week for four weeks.After complete treatment,the number of lesions reduced by 71.4% in the blue group,in contrast to 19.5% in the red group.No obvious side effects were observed during and one month after the treatment,except for some mild dryness mentioned by several patients.

关键词： Acne vulgaris light emitting diode phototherapy portable light sources

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Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy

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Acta Pharmaceutica Sinica B 2022年第1期12卷 406-423页

作者： Shuangquan Gou Nanxi Chen Xiaoai Wu Menghang Zu Shixiong Yi Binwu Ying Fangyin Dai Bowen Ke Bo Xiao Laboratory of Anesthesiology&Critical Care Medicine Department of AnesthesiologyWest China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Silkworm Genome Biology College of SericultureTextile and Biomass SciencesSouthwest UniversityChongqing 400715China Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing School of Materials and EnergySouthwest UniversityChongqing 400715China Department of Nuclear Medicine West China HospitalSichuan UniversityChengdu 610041China Department of Laboratory Medicine West China HospitalSichuan UniversityChengdu 610041China

Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin(DOX)-loaded silk fibroinbased nanoparticles(NPs) with surface functionalization by photosensitizer(N770). The obtained nanotheranostics(N770-DOX@NPs) had desirable particle size(157 nm) and negative surface charge(-25 m V). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli(acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared(NIR) fluorescence imaging, photothermal imaging,and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumorretardation effect among all treatment groups based on tumor-bearing mouse models and a patientderived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imagingguided mitochondrial phototherapy(photothermal therapy and photodynamic therapy) and chemotherapy.Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors.

关键词： Quadruple responsibility Silk fiborin Nanotheranostic Oxygen self-generation Mitochondrial targeting phototherapy Chemotherapy Cancer

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Engineering naphthalimide-cyanine integrated near-infrared dye into ROS-responsive nanohybrids for tumor PDT/PTT/chemotherapy

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Bioactive Materials 2022年第8期7卷 42-51页

作者： Tongxia Jin Di Cheng Guanyu Jiang Wenqian Xing Peiwen Liu Bin Wang Weiping Zhu Haitao Sun Zhenrong Sun Yufang Xu Xuhong Qian State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of Chemical BiologySchool of PharmacyEast China University of Science and Technology130 Meilong RoadShanghai200237PR China State Key Laboratory of Precision Spectroscopy School of Physics and Electronic ScienceEast China Normal University500 Dongchuan RoadShanghai200241PR China Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of PharmacyEast China University of Science and Technology130 Meilong RoadShanghai200237China

Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents.Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT.Herein,we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton.The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820.Furthermore,ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica(RMON)to construct nanomedicine NBD&ML@RMON,which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.

关键词： Near-infrared dye Integration strategy phototherapy Combination therapy Drug delivery system

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