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Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

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Chinese Chemical Letters 2024年第4期35卷 292-297页

作者： Yi Cao Xiaojiao Ge Yuanyuan Wei Lulu He Aiguo Wu Juan Li ningbo Key Laboratory of Biomedical Imaging Probe Materials and technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China University of Chinese Academy of sciences Beijing 100049China Advanced Energy science and technology Guangdong Laboratory Huizhou 516000China

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.

关键词： Neuropeptide-drug conjugate Tumor penetration Calcium deposition Tumor inhibition Triple-negative breast cancer

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Repeatability and reproducibility of corneal higher-order aberrations measurements after small incision lenticule extraction using the Scheimpfug-Placido topographer

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Eye and Vision 2024年第1期10卷 1-9页

作者： Rui Ning Rongrong Gao David PPiñero Jun Zhang Qingyi Gao Yili Jin Yiran Wang Chenxiao Wang Jinhai Huang Eye Hospital and School of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhouZhejiangChina Eye Institute and Department of Ophthalmology Eye and ENT HospitalFudan UniversityShanghaiChina Group of Optics and Visual Perception Department of OpticsPharmacology and AnatomyUniversity of AlicanteAlicanteSpain NHC Key Laboratory of Myopia(Fudan University) Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghaiChina Shanghai Research Center of Ophthalmology and Optometry ShanghaiChina

Background:To evaluate the precision of corneal higher-order aberrations measurements after small incision lenticule extraction(SMILE)using the Sirius Scheimpfug-Placido topographer(CSO,Italy).Methods:Seventy-fve eyes from 75 postoperative subjects were included in this prospective *** consecutive corneal aberrometric measurements were obtained with the Scheimpfug-Placido topographer by two experienced operators to assess intra-and inter-observer *** within-subject standard deviation(Sw),test-retest repeatability(TRT)and the intraclass correlation coefcient(ICC)were ***:For intraobserver repeatability of anterior and total corneal aberrations,all ICCs were more than 0.922,except for trefoil(0.722 to 0.768).The ICCs of total root mean square(RMS),coma Z(3,±1),and spherical aberration Z(4,0)were over 0.810 while higher-order RMS,trefoil Z(3,±3),and astigmatism II Z(4,±2)were below 0.634 for posterior corneal surface *** Sw values for all types of aberrations were equal to or below 0.07μ*** interobserver reproducibility,all TRT values were no more than 0.12μm,0.05μm,and 0.11μm for anterior,posterior,and total corneal aberrations,*** ICC values ranged from 0.875 to 0.989,from 0.686 to 0.976 and over 0.834 for anterior,posterior,and total corneal aberrations,***:The repeatability of measurements of anterior and total corneal aberrations with the Sirius system in corneas after SMILE surgery was high,except for *** was some variability in posterior corneal aberrometric *** reproducibility of corneal aberrometric measurements was observed between measurements of both examiners,except for trefoil,with poor to moderate reproducibility.

关键词： Sirius Higher-order aberrations Repeatability Reproducibility Small incision lenticule extraction

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Phase separation of Nur77 mediates XS561-induced apoptosis by promoting the formation of Nur77/Bcl-2 condensates

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1204-1221页

作者： Xiaohui Chen Meichun Gao Yongzhen Xia Xin Wang Jingbo Qin Hongying He Weirong Liu Xiaowei Zhang Shuangzhou Peng Zhiping Zeng Ying Su Xiaokun Zhang School of Pharmaceutical science Fujian Provincial Key Laboratory of Innovative Drug Target ResearchXiamen UniversityXiamen 361002China NucMito Pharmaceuticals Co. Ltd.Xiamen 361000China Department of Clinical Laboratory the Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

The orphan nuclear receptor Nur77 is a critical regulator of the survival and death of tumor *** pro-death effect of Nur77 can be regulated by its interaction with Bcl-2,resulting in conversion of Bcl-2 from a survival to *** Bcl-2 is overexpressed in various cancers preventing them from apoptosis and promoting their resistance to chemotherapy,targeting the apoptotic pathway of Nur77/Bcl-2 may lead to new cancer ***,we report our identification of XS561 as a novel Nur77 ligand that induces apoptosis of tumor cells by activating the Nur77/Bcl-2 *** vitro and animal studies revealed an apoptotic effect of XS561 in a range of tumor cell lines including MDA-MB-231 triple-negative breast cancer(TNBC)and MCF-7/LCC2 tamoxifen-resistant breast cancer(TAMR)in a Nur77-dependent *** studies showed XS561 potently induced the translocation of Nur77 from the nucleus to mitochondria,resulting in mitochondria-related ***,XS561-induced accumulation of Nur77 at mitochondria was associated with XS561 induction of Nur77 phase separation and the formation of Nur77/Bcl-2 ***,our studies identify XS561 as a new activator of the Nur77/Bcl-2 apoptotic pathway and reveal a role of phase separation in mediating the apoptotic effect of Nur77 at mitochondria.

关键词： XS561 Nur77 Bcl-2 Apoptosis Mitochondria Phase separation TNBC TAMR

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D-type neuropeptide decorated AIEgen/RENP hybrid nanoprobes with light-driven ROS generation ability for NIR-Ⅱ fluorescence imaging-guided through-skull photodynamic therapy of gliomas

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Aggregate 2024年第1期5卷 185-195页

作者： Xuelu He Yuan Luo Yanying Li Yuanbo Pan Ryan T.K.Kwok Lulu He Xiaolin Duan Pengfei Zhang Aiguo Wu Ben Zhong Tang Juan Li ningbo Key Laboratory of Biomedical Imaging Probe Materials and technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingboP.R.China Guangdong Key Laboratory of Nanomedicine Shenzhen Engineering Laboratory of Nanomedicine and NanoformulationsCAS-HK Joint Lab for BiomaterialsResearch Laboratory for Biomedical Optics and Molecular ImagingShenzhen Key Laboratory for Molecular ImagingCAS Key Lab for Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenP.R.China Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced StudyThe Hong Kong University of Science and Technology(HKUST)KowloonP.R.China School of science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhenP.R.China

Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in ***-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a promising therapeutic strategy for least-invasive treatment of glioma,which involves local irradiation of the tumor using an external near-infrared(NIR)***,most AIE photosensitizers suffered from poorly penetration of the visible light excitation,bad spatiotemporal resolution in deep tissues and low efficient blood-brain barrier(BBB)crossing ability,which greatly limited the clinical practice of AIE photosensitizers for especially deep-seated brain tumor *** this work,we developed a multifunctional NIR-driven theranostic agent through hybrid of AIE photosensitizers TIND with rare-earth doping nanoparticles(RENPs)NaGdF4:Nd/Yb/Tm with up/down dual-mode conversion *** theranostic agent was further decorated with D-type neuropeptide DNPY for crossing BBB and targeting *** the 808-nm light irradiation,the down-conversion NIR-II luminescence could indicate the position glioma and the upconversion NIR-I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in *** results demonstrate that the integration of Dtype neuropeptide,AIE photosensitizers and RENPs could be promising candidates for in vivo NIR-II fluorescence image-guided through-skull PDT treatments of brain tumors.

关键词： aggregation-induced emission D-type neuropeptide glioma photodynamic therapy rare-earth doping nanoparticles

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用于常见疾病成像的纳米材料造影剂

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science China Materials 2024年第4期67卷 1288-1291页

作者：邢洁李子厚姚俊列吴爱国 ningbo Key Laboratory of Biomedical Imaging Probe Materials and technology Zhejiang International Cooperation Base of Biomedical Materials Technology and Application Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices Ningbo Cixi Institute of Biomedical Engineering Zhejiang Engineering Research Center for Biomedical Materials Ningbo Institute of Materials Technology and Engineering Chinese Academy of Sciences Advanced Energy science and technology Guangdong Laboratory

生物医学精准诊断对于疾病的有效治疗十分重要.纳米基成像造影剂具有灵敏度高、特异性强、生物相容性好等特点,在生物医学成像诊断中具有巨大的临床转化潜力.目前,尽管研究者们构筑了大量的纳米基探针材料作为疾病诊断造影剂,但纳米材... 详细信息

生物医学精准诊断对于疾病的有效治疗十分重要.纳米基成像造影剂具有灵敏度高、特异性强、生物相容性好等特点,在生物医学成像诊断中具有巨大的临床转化潜力.目前,尽管研究者们构筑了大量的纳米基探针材料作为疾病诊断造影剂,但纳米材料造影剂在临床转化方面仍然面临极大的挑战.这里我们主要概述了不同生物医学成像类型的纳米基造影剂所面临的问题,并针对这些难题提出了应对方案和未来的研究重点,最后对纳米基造影剂的临床转化前景进行了展望.

关键词：造影剂生物医学成像疾病诊断应对方案生物相容性纳米材料临床转化有效治疗

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Black phosphorus nanosheets-based tumor microenvironment responsive multifunctional nanosystem for highly efficient photo-/sono-synergistic therapy of non-Hodgkin lymphoma

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Chinese Chemical Letters 2023年第10期34卷 223-228页

作者： Xueli Zhu Shengmin Zhang Yi Cao Xiaojiao Ge Yi Huang Feng Mao Bo Chen Juan Li Youfeng Xu Aiguo Wu Department of Ultrasound Central LaboratoryNingbo First HospitalNingbo 315000China Cixi Institute of Biomedical Engineering International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringCASNingbo 315201China University of Chinese Academy of sciences Beijing 100049China

Finding improved therapeutic protocols against non-Hodgkin’s lymphoma(NHL) remains an unmet clinical demand. Phototherapy is a promising alternative treatment for traditional clinical therapeutic methods, but the limited tissue penetration blocks the therapeutics. Inspired by the excellent physical and chemical properties of black phosphorus nanosheets(BPNSs), a fluorescence and thermal imaging guided photo-/sono-synergistic treatment platform BPNSs@PEG-SS-IR780/RGD is developed. This ingenious multifunctional theranostic platform not only exhibits outstanding photothermal conversion efficiency and highly efficient reactive oxygen species generation, but also has good biocompatibility, tumor-targeting and tumor microenvironment responsiveness. In addition, BPNSs@PEG-SS-IR780/RGD could actively target the tumor sites and generate excellent photothermal, photodynamic and sonodynamic therapeutic efficacy. Both in vitro and in vivo experiments indicate that BPNSs@PEG-SS-IR780/RGD can be a promising nanomaterial for NHL imaging and therapy. Taken together, this study not only expands the application field of black phosphorus materials, but also provides a possibility to design a new generation of NHL treatment regimens with clinical application potential.

关键词： Non-Hodgkin’s lymphoma Black phosphorus IR780 Phototherapy Sonodynamic therapy

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Ultrasound-visualized nanocarriers with siRNA for targeted inhibition of M2-like TAM polarization to enhance photothermal therapy in NSCLC

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Nano Research 2023年第1期16卷 882-893页

作者： Wenhao Lv Chen Xu Hao Wu Yangyang Zhu Ozioma Udochukwu Akakuru Hui Du Fang Nie Aiguo Wu Juan Li Ultrasound Medical Center Lanzhou University Second HospitalGansu Province Clinical Research Center for UltrasonographyGansu Province Medical Engineering Research Center for Intelligence UltrasoundLanzhou 730000China Cixi Institute of Biomedical Engineering International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringCASNingbo 315201China

Photothermal therapy(PTT)has received a lot of attention as a promising strategy for eliminating tumors ***,the unavoidable inflammatory response during the treatment might result in a high concentration of M2-like tumor-associated macrophages(TAMs),increasing the risk of tumor recurrence and *** address this problem,gold-based nanocarriers(PGMP-small interfering RNA(siRNA)nanoparticles(NPs))containing STAT6siRNA,that inhibited M2-like TAM polarization,were designed and investigated for PTT and gene therapy of non-small cell lung cancer(NSCLC).In an NSCLC model,the nanocarriers demonstrated excellent siRNA delivery ability and a high gene transfection rate of up to 90%in macrophages,thus inhibiting the polarization of about 87%of M2-like TAMs and effectively suppressing the invasion and metastasis of ***,the unique gold nanosphere structure offered improved PTT and contrast-enhanced ultrasound imaging,thus contributing to the efficient elimination and real-time monitoring of the tumor *** nanocarriers with combined gene and photothermal therapeutic capabilities improved the efficacy of single-modality treatment,and showed the potential to inhibit cancer cell recurrence and metastasis to ultimately cure NSCLC.

关键词： gold-based nanocarrier small interfering RNA(siRNA)delivery photothermal therapy M2-like tumor-associated macrophages(TAMs) contrast-enhanced ultrasound imaging non-small cell lung cancer(NSCLC)

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HPDA/Zn as a CREB Inhibitor for Ultrasound imaging and Stabilization of Atherosclerosis Plaque+

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Chinese Journal of Chemistry 2023年第2期41卷 199-206页

作者： Linzi Chen Zhenqi Jiang Lifei Yang Ye Fang Shuwei Lu Ozioma U.Akakuru Shuaishuai Huang Juan Li Suya Ma Aiguo Wu ningbo Yinzhou No.2 Hospital NingboZhejiang 315192China Cixi Institute of Biomedical Engineering International Cooperation Base of Biomedical Materials Technology and ApplicationCAS Key Laboratory of Magnetic Materials and DevicesZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingboZhejiang 315201China School of Medical technology Institute of Engineering MedicineBeijing Institute of TechnologyBeijing 100081China

Thrombosis,secondary to rupture of unstable plaque,is a fatal risk factor for myocardial infarction and ischemic *** present,more novel methods are needed for the diagnosis and treatment of vulnerable ***,we report a hollow polydopamine/Zn(HPDA/Zn)ultrasound contrast *** western-blot,Elisa,and other experiments,we found that in addition to having a good contrast-enhancement capability in ultrasound imaging in vitro and in vivo,HPDA/Zn also has the effect of reducing the expres-sion of *** protein and its downstream-regulated proteins and factors are closely related to the stability of ***/Zn has the effect of reducing the expression of CREB protein,which leads to the decrease of expression of MMP-9,the regulatory pro-tein downstream of the CREB *** addition,it also reduces the secretion of inflammatory factors hs-CRP and ***,HPDA/Zn can stabilize plaque by inhibiting CREB and reducing plaque vulnerable markers and inflammatory *** a word,HPDA/Zn is a kind of ultrasound contrast agent,which can stabilize plaques by inhibiting CREB protein.

关键词： Atherosclerosis Zinc Polymerization CREB Nanoparticles Ultrasound imaging

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Mn-doped Ti-based MOFs for magnetic resonance imaging-guided synergistic microwave thermal and microwave dynamic therapy of liver cancer

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Bioactive Materials 2023年第9期27卷 72-81页

作者： Qiongyu Qin Ming Yang Yu Shi Haijing Cui Chunshu Pan Wenzhi Ren Aiguo Wu Jianqing Hu School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhou510640GuangdongPR China Cixi Institute of Biomedical Engineering International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Science(CAS)Key Laboratory of Magnetic Materials and Devices and Zhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringCAS1219 ZhongGuan West RoadNingbo315201PR China Advanced Energy science and technology Guangdong Laboratory Huizhou516000PR China Department of Radiology Ningbo No.2 HospitalNingbo315010PR China

Currently,precise ablation of tumors without damaging the surrounding normal tissue is still an urgent problem for clinical microwave therapy of liver ***,we synthesized Mn-doped Ti MOFs(Mn-Ti MOFs)nanosheets by in-situ doping method and applied them for microwave *** thermal imaging results indicate Mn-Ti MOFs can rapidly increase the temperature of normal saline,attributing to the porous structure improving microwave-induced ion collision ***,Mn-Ti MOFs show higher 1O2 output than Ti MOFs under 2 W of low-power microwave irradiation due to the narrower band-gap after Mn *** the same time,Mn endows the MOFs with a desirable T1 contrast of magnetic resonance imaging(r2/r1=2.315).Further,results on HepG2 tumor-bearing mice prove that microwave-triggered Mn-Ti MOFs nearly eradicate the tumors after 14 days of *** study offers a promising sensitizer for synergistic microwave thermal and microwave dynamic therapy of liver cancer.

关键词： Metal-organic framework Titanium-based nanomaterials Microwave dynamic therapy Microwave thermal therapy MR image

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Construction of chimeric viruses based on pepper mild mottle virus using a modiffed Cre/loxP system

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Journal of Integrative Agriculture 2022年第8期21卷 2456-2463页

作者： YIN Yue-yan HUA Meng-ying ZHAO Kuang-jie WAN Qiong-lian BU Shan LU Yu-wen ZHENG Hong-ying RAO Shao-fei YAN Fei PENG Jie-jun CHEN Hai-ru CHEN Jian-ping College of Plant Protection Yunnan Agricultural UniversityKunming 650201P.R.China Institute of Alpine Economic Plants Yunnan Academy of Agricultural SciencesLijiang 674100P.R.China State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agroproducts Institute of Plant VirologyNingbo UniversityNingbo 315211P.R.China Longping Branch of Graduate College Hunan UniversityChangsha 410125P.R.China

Cre/loxP,a site-specific recombination system,has been widely used for various purposes,including chromosomal translocations,generation of marker-free transgenic plants,tissue-specific activation of a reporter gene and efficient heterologous gene expression in ***,stable or transient expression of Cre recombinase in plants can cause chlorosis or ***,we describe a modified Cre/loxP recombination system using a DNA fragment flanked with loxP sites in the same orientation in which necrosis induced by Cre recombinase in Nicotiana benthamiana leaves was *** modified system was successfully used to create functional GFP-tagged pepper mild mottle virus(PMMoV)and a chimeric virus with coat protein(CP)substitution assembled from separate pro-vector *** results provide a new strategy and flexible technique to construct chimeric virus and infectious clones for plant viruses with large genomes.

关键词： pepper mild mottle virus Cre/loxP necrosis infectious cDNA clone chimeric virus

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