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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

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

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

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

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

Effect of the structure of ginsenosides on the in vivo fate of their liposomes

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Asian Journal of Pharmaceutical Sciences 2022年第2期17卷 219-229页

作者： Chen Chen Jiaxuan Xia Hongwei Ren Anni Wang Ying Zhu Ru Zhang Zicheng Gan Jianxin Wang Department of Pharmaceutics School of PharmacyFudan University&Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai 201203China Institute of Tropical Medicine Guangzhou University of Chinese MedicineGuangzhou 510006China Institute of Integrated Chinese and Western Medicine Fudan UniversityShanghai 200040China

To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of *** results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their *** pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in *** C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 *** to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting *** results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.

关键词： Ginsenosides Liposomes Structure activity relationship Rg3 liposomes Long circulation tumor targeting Glut 1

A novel monoclonal antibody,CC4,targeting a conserved epitope of CEACAMs significantly inhibits tumor growth of colorectal cancer

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A novel monoclonal antibody,CC4,targeting a conserved epitop...

Phospholipid membrane-decorated deep-penetrated nanocatalase relieve tumor hypoxia to enhance chemo-photodynamic therapy

第十一次中国生物物理学术大会暨第九届全国会员代表大会

作者： Shu Xing 1 ,Xiyun Yan National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,15 Datun Road,Beijing 100101,China

＜正＞Belonging to the immunoglobulin superfamily of cell adhesion molecules,carcinoembryonic antigen related cell adhesion molecules（CEACAMs）have been found associated with

关键词： CEACAMs monoclonal antibodies colorectal cancer cancer therapy epitope tumor targeting in vivo optical imaging of tumor xenografted animal model

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cnki会议

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2246-2257页

作者： Junjing Yin Haiqiang Cao Hong Wang Kaoxiang Sun Yaping Li Zhiwen Zhang School of Pharmacy Yantai UniversityYantai 264005China State Key Laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Yantai Key Laboratory of Nanomedicine&Advanced Preparations Yantai Institute of Materia MedicaYantai 264000China

Hypoxia is a serious impediment to current treatments of many malignant ***,an antioxidant enzyme,is capable of decomposing endogenous hydrogen peroxide(H2O2)into oxygen for tumor reoxygenation,but suffered from in vivo instability and limited delivery to deep interior hypoxic regions in ***,a deep-penetrated nanocatalase-loading DiIC18(5,DiD)and soravtansine(Cat@PDS)were provided by coating catalase nanoparticles with PEGylated phospholipids membrane,stimulating the structure and function of erythrocytes to relieve tumor hypoxia for enhanced chemophotodynamic *** intravenous administration,Cat@PDS preferentially accumulated at tumor sites,flexibly penetrated into the interior regions of tumor mass and remarkably relieved the hypoxic status in ***,the Cat@PDS+laser treatment produced striking inhibition of tumor growth and resulted in a 97.2%suppression of lung ***,the phospholipids membrane-coated nanocatalase system represents an encouraging nanoplatform to relieve tumor hypoxia and synergize the chemophotodynamic cancer therapy.

关键词： Photodynamic therapy tumor hypoxia Catalase tumor penetration Drug delivery Nanoparticle tumor targeting Cancer metastasis Cancer therapy

Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2110-2124页

作者： Jin Li Diane J.Burgess Department of Pharmaceutical Sciences University of ConnecticutStorrsCT 06269-3092USA

The complex tumor microenvironment is a most important factor in cancer *** biological microenvironment is composed of a variety of barriers including the extracellular matrix and associated cells such as endothelia cells,pericytes,and cancer-associated *** strategies can be utilized to enhance nanoparticle-based drug delivery and distribution into tumor tissues addressing the extracellular matrix or cellular *** addition to the biological microenvironment,the immunological conditions around the tumor tissue can be very complicated and cancer cells have various ways of evading immune *** drug delivery systems can enhance cancer immunotherapy by tuning the immunological response and memory of various immune cells such as T cells,B cells,macrophages,and dendritic *** this review,the main components in the tumor biological and immunological environment are *** focus is on recent advances in nanoparticle-based drug delivery systems towards targets within the tumor microenvironment to improve cancer chemotherapy and immunotherapy.

关键词： tumor microenvironment Nanoparticles Drug delivery tumor immunology tumor treatment tumor targeting Immunotherapy Combinational therapy