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R11 peptides can promote the molecular imaging of spherical nucleic acids for bladder cancer margin identification

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Nano Research 2022年第3期15卷 2278-2287页

作者： Minghai Ma Pu Zhang Xiao Liang Daxiang Cui Qiuya Shao Haibao Zhang Mengzhao Zhang Tao Yang Lu Wang Nan Zhang Minxuan Jing Lu Zhang Weichao Dan Rundong Song Xi Liu Jiatao Hao Yuhang Chen Lijiang Gu Lei Wang Jinhai Fan Department of Urology The First Affiliated HospitalXi’an Jiaotong UniversityXi’an 710061China Department of Urology Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310014China Department of Thoracic Surgery Tangdu HospitalAir Force Medical UniversityXi’an 710038China Department of Bio-Nano-Science and Engineering National Key Laboratory of Nano/Micro Fabrication TechnologyInstitute of Micro-Nano Science and TechnologyShanghai Jiao Tong UniversityShanghai 200240China

One of the critical problems in bladder cancer(BC)management is the local recurrence of ***,achieving the accurate delineation of tumor margins intraoperatively remains extremely difficult due to the lack of effective tumor margin recognition ***,survivin molecular beacon(MB)and R11 peptide-linked spherical nucleic acids(SNAs)were synthesized as nanoprobes(AuNP-MB@R11)for sensitive detection of BC *** properties proved that R11 peptides and survivin MB were successfully loaded onto the surface of ***-MB@R11 had good stability against nuclease activity and high sensitivity and specificity to detect survivin single strand DNA(ssDNA)in *** to cytology,R11 peptides could increase the BC targeting ability and membrane penetrability of ***,R11 peptides significantly promoted the disintegration of lysosomes and the release of SNAs to enhance fluorescence imaging *** RNA sequencing proved that some genes and pathways related to endocytosis and lysosomes were significantly regulated,such as AGPAT5,GPD1L,and *** orthotopic BC models and a clinical sample from a patient with BC,AuNP-MB@R11 showed a more legible cancerous fluorescence margin and offered remarkably improved detection compared to those achieved by SNAs.R11 peptide-linked SNAs present promising potential to identify BC margin,which may help to improve the R0 resection rate in surgery and improve patients’quality of life.

关键词： R11 peptides molecular beacons spherical nucleic acids tumor targeting lysosome escape bladder cancer

Palladium nanoplates scotch breast cancer lung metastasis by constraining epithelial-mesenchymal transition

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National Science Review 2021年第7期8卷 124-136页

作者： Shunhao Wang Jingchao Li Mei Chen Liting Ren Wenya Feng Lining Xu Xiaolan Chen Tian Xia Nanfeng Zheng Sijin Liu State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences State Key Laboratory for Physical Chemistry of Solid Surfaces Collaborative Innovation Center of Chemistry for Energy Materials Department of Chemistry Xiamen University College of Materials Science and Engineering Hunan University Division of Nanomedicine Department of Medicine California Nano Systems Institute University of CaliforniaLos Angeles

Metastasis accounts for the majority of cancer deaths in many tumor types including breast ***-mesenchymal transition(EMT) is the driving force for the occurrence and progression of metastasis, however, no targeted strategies to block the EMT program are currently available to combat metastasis. Diverse engineered nanomaterials(ENMs) have been reported to exert promising anti-cancer effects, however, no ENMs have been designed to target EMT. Palladium(Pd) nanomaterials, a type of ENM, have received substantial attention in nanomedicine due to their favorable photothermal performance for cancer therapeutics. Herein, Pd nanoplates(Pd PL) were found to be preferentially biodistributed to both primary tumors and metastatic tumors. Importantly, Pd PL showed a significant inhibition of lung metastasis with and without near-infrared(NIR) irradiation. Mechanistic investigations revealed that EMT was significantly compromised in breast cancer cells upon the Pd PL treatment, which was partially due to the inhibition of the transforming growth factor-beta(TGF-β) signaling. Strikingly, the Pd PL was found to directly interact with TGF-β proteins to diminish TGF-β functions in activating its downstream signaling, as evidenced by the reduced phosphorylation of Smad2. Notably,TGF-β-independent pathways were also involved in undermining EMT and other important biological processes that are necessary for metastasis. Additionally, NIR irradiation elicited synergistic effects on PdPL-induced inhibition of primary tumors and metastasis. In summary, these results revealed that the Pd PL remarkably curbed metastasis by inhibiting EMT signaling, thereby indicating the promising potential of Pd PL as a therapeutic agent for treating breast cancer metastasis.

关键词： palladium nanoplates tumor targeting lung metastasis epithelial-mesenchymal transition TGF-β

Preparation and functional study of pH-sensitive amorphous calcium phosphate nanocarriers

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Chinese Journal of Chemical Engineering 2022年第8期35卷 244-252页

作者： Baolong Niu Min Li Jianhong Jia Lixuan Ren Xin Gang Bin Nie Yanying Fan Xiaojie Lian Wenfeng Li College of Materials Science and Engineering Taiyuan University of TechnologyTaiyuan 030024China Key Laboratory of Interface Science and Engineering in Advanced Materials Taiyuan University of TechnologyTaiyuan 030024China Department of Biomedical Engineering Research Center for Nano-biomaterials&Regenerative MedicineCollege of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan 030024China Shanxi Key Laboratory of Material Strength&Structural Impact Institute of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan 030024China School of Basic Medical Sciences Shanxi Medical UniversityTaiyuan 030001China

Recently,multifunctional nanoparticles have shown great prospects in cancer treatment,which have the ability to simultaneously deliver the drug,image and target tumor *** this paper,we designed a luminescent nanoparticles platform based on hydrothermal hyaluronic acid/amorphous calcium phosphate(HA-FCNs/ACP)with multifunctional properties for drug delivery,bio-imaging,and targeting ***-FCNs/ACP shows an ability to load curcumin(Cur)with pH-sensitive responsive drug release behavior and excellent ***-FCNs/ACP dispersed in the cytoplasm through the overexpressed CD44 receptor that is actively targeted into human lung cancer cells(A549 cells).Meanwhile,the viability of A549 cells was significantly inhibited in *** prepared HA-FCNs and HA-FCNs/ACP both exhibit excellent targeted bioimaging performance on cancer ***,the as-prepared nanoparticles have promising applications in treating tumor disease.

关键词： Hyaluronic acid Amorphous calcium phosphate Fluorescent carbon nanoparticles pH-sensitive tumor targeting

Current strategies for improving limitations of proteolysis targeting chimeras

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Chinese Chemical Letters 2023年第6期34卷 144-156页

作者： Chunlan Pu Shirui Wang Lei Liu Zhonghui Feng Hongjia Zhang Qianyuan Gong Yueshan Sun Yuanbiao Guo Rui Li Medical Research Center The Third People’s Hospital of ChengduThe Affiliated Hospital of Southwest Jiaotong UniversityThe Second Chengdu Hospital Affiliated to Chongqing Medical UniversityChengdu 610031China State Key Laboratory of Biotherapy Collaborative Innovation Center of Biotherapy and Cancer CenterWest China Hospital of Sichuan UniversityChengdu 610041China

Proteolysis targeting chimeras(PROTACs)are bifunctional degrader molecules via hijacking the ubiquitinproteasome system(UPS)to specifically eliminate targeted *** have gained momentum as a new modality of attractive technologies in the drug discovery landscape,since it allows to degrade disease-related proteins *** some PROTACs drugs reached the clinical research,they are still facing some bottlenecks and challenges that should not be neglected,such as poor oral bioavailability and potential toxic side *** overcome these limitations,herein,we provide an overview of recent strategies for improving the durability of PROTACs by enhancing cell permeability and reducing toxic side ***,the impact of these strategies on improving oral bioavailability as well as their advantages and drawbacks will also be *** review will give a useful reference toolbox for PROTACs design and further promote its clinical application.

关键词： PROTACs Targeted protein degradation Oral bioavailability Cell permeability tumor targeting

Liposome-based anchoring and core-encapsulation for combinatorial cancer therapy

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Chinese Chemical Letters 2022年第9期33卷 4191-4196页

作者： Qingqing Xiao Xiaotong Li Chang Liu Yi Yang Yuqi Hou Ying Wang Mengxiang Su Wei He School of Pharmacy China Pharmaceutical UniversityNanjing 211198China

Downregulated pro-apoptotic protein in cancer cells compromises the chemotherapy by a cytotoxic ***,we report co-delivery of a pro-apoptotic protein,caspase 3(Cas 3),and cytotoxic agent,oridonin(ORD),for synergistic cancer treatment,using a method of liposome-based anchoring and core ***,ORD is modified with hyaluronic acid(HA)to improve its ***,the targeted co-delivery system is prepared by assembling the conjugate HA-ORD onto the Cas 3-loaded liposomes,which the surface HA can target the CD44 receptor on cancer *** vitro,the co-loaded liposomes(120 nm)are specifically taken up by 4T1 cells and endow a 1.5-fold increase of Cas *** intravenous injection into the tumor-bearing mice,the liposomes accumulate in the tumor with high efficacy and significantly inhibit tumor growth via promoting apoptosis and anti-proliferation of cancer ***,the co-delivery works synergistically by upregulating the activated Cas form,cleaved-Cas 3.

关键词： Liposomes Co-delivery Chemotherapy Pro-apoptotic protein tumor targeting

Hyperthermia based individual in situ recombinant vaccine enhances lymph nodes drainage for de novo antitumor immunity

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3398-3409页

作者： Cuixia Zheng Xinxin Liu Yueyue Kong Lei Zhang Qingling Song Hongjuan Zhao Lu Han Jiannan Jiao Qianhua Feng Lei Wang Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang 471009China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China Department of Gynecology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China tumor Immunity and Biomaterials Advanced Medical Center Zhengzhou UniversityLuoyang 471009China

The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes(LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin(SV) adjuvant loaded Au nanocages(AuNCs)as cores(AuNCs/SV) and folic acid modified thermal-sensitive liposomes(FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy(PTT) induced the release of tumor-derived protein antigens(TDPAs) and the shedding of FATSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine(AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination.

关键词： Au nanocages Simvastatin Photothermal therapy tumor-derived protein antigens Recombinant vaccine tumor targeting Lymph node drainage De novo antitumor immunity

Facile synthesis of size-tunable stable nanoparticles via click reaction for cancer drug delivery

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Science China Chemistry 2014年第4期57卷 633-644页

作者： CAO Ming LIU XiangRui TANG JianBin SUI MeiHua SHEN YouQing Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineering of Zhejiang University Department of Chemical and Biological Engineering Zhejiang University

The stability and size of polymeric nanoparticles are two of the most important parameters determining their pharmacokinetics and tumor/drug accumulation efficiency in cancer-drug delivery. Herein, we report a facile one-pot synthesis of crosslinked nanoparticles(CNPs) with tunable sizes and polyethylene glycol(PEG) shells via click reactions. Simply by adjusting the contents of the macromonomer(PEG monoacrylate) in its reaction with ethylene diacrylate and a crosslinker containing hexa-thiols groups, the sizes of the resulting PEGylated crosslinked nanoparticles could be easily tuned from 10 to 90 nm. These nanoparticle cores could encapsulate hydrophobic drugs such as doxorubicin(DOX), and the unreacted thiol and acrylate groups could be used for drug conjugation or labeling. Thus, the nanoparticles provide a multifunctional platform for drug delivery. In vivo studies showed that the larger nanoparticles(about 83.7 nm) had a much longer blood-circulation time and better tumor-targeting efficiency. One of our most important findings was that the drug encapsulated in the crosslinked nanoparticles, even though little was released at pH 7.4 under in vitro conditions, had much faster blood clearance than the nanoparticles' carrier, suggesting that drug release in the bloodstream was significant.

关键词： crosslinked nanoparticles facile synthesis size effect pharmacokinetics tumor targeting

Cell membrane coated-nanoparticles for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3233-3254页

作者： Yingping Zeng Sufen Li Shufen Zhang Li Wang Hong Yuan Fuqiang Hu College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China

Cancer immunotherapy can effectively inhibit cancer progression by activating the autoimmune system, with low toxicity and high effectiveness. Some of cancer immunotherapy had positive effects on clinical cancer treatment. However, cancer immunotherapy is still restricted by cancer heterogeneity, immune cell disability, tumor immunosuppressive microenvironment and systemic immune toxicity. Cell membrane-coated nanoparticles(CMCNs) inherit abundant source cell-relevant functions, including “self” markers, cross-talking with the immune system, biological targeting, and homing to specific regions. These enable them to possess preferred characteristics, including better biological compatibility, weak immunogenicity, immune escaping, a prolonged circulation, and tumor ***, they are applied to precisely deliver drugs and promote the effect of cancer *** the review, we summarize the latest researches of biomimetic CMCNs for cancer immunotherapy,outline the existing specific cancer immune therapies, explore the unique functions and molecular mechanisms of various cell membrane-coated nanoparticles, and analyze the challenges which CMCNs face in clinical translation.

关键词： Biomimetic Cell membrane-coated nanoparticles Drug delivery “Self”markers tumor targeting Cancer immunotherapy Cancer vaccines Immune checkpoint blockade inhibitors

Self-Assembled DNA Nanostructures for Drug Delivery

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Chinese Journal of Chemistry 2016年第3期34卷 265-272页

作者： Ruokun Jia Ting Wang Qiao Jiang Zhengang Wang Chen Song Baoquan Ding College of Chemical Engineering Northeast Dianli University Jilin Jilin 132012 China National Center for Nanoscience and Technology 11 Bei YiTiao ZhongGuanCun 100190 Beijing China

Due to the uniform nanoscale sizes, well-defined shapes, precise spatial addressability and prominent biocom- patibility, self-assembled DNA nanostructures have been intensively studied for their biomedical applications. This review summarizes the recent development ofDNA nanotechnology in cancer therapy, and discusses the challenges and potential strategies to advance the methodologies of cancer treatments.

关键词： DNA nanostructures DNA nanotechnology drug delivery tumor targeting cancer therapy