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An aptamer-driven DNA nanodevice for improved delivery of synthetic immunostimulants

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Nano Research 2024年第10期17卷 9078-9083页

作者： Dejie Lu Zhenghan Di Lele Li Jian Zhao Li Zheng Guangxi Engineering Center in biomedical Materials for Tissue and Organ Regeneration Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and ApplicationGuangxi Key Laboratory of Regenerative MedicineThe First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China CAS key laboratory for biomedical effects of nanomaterials and nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Efficient delivery of therapeutics to immune cells remains a formidable challenge for cancer *** this work,we demonstrate that an aptamer-driven DNA nanodevice,constructed through linkage of a synthetic immunostimulant(Toll-like receptor 9 agonist:CpG motif)to an aptamer,could significantly enhance the immunostimulatory activity by facilitating the uptake and retention of therapeutics in *** administration of the DNA nanodevice results in efficient tumor growth inhibition in both breast cancer and melanoma mouse *** studies suggest that the DNA nanodevice leads to reeducation of tumor-associated macrophages and ultimately to reversing the tumor immune *** strategy for aptamer-mediated and vehicle-free delivery of immunostimulatory oligonucleotides provides a potential platform for cancer immunotherapy.

关键词： aptamer immunostimulatory oligonucleotides DNA nanodevice tumor-associated macrophages cancer therapy

Screened peptides from one-bead one-compound technique extend half-life of peptide drugs in circulation through binding to albumin

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Chinese Chemical Letters 2024年第3期35卷 384-388页

作者： Yi-Jing Li Lingze Zhang Ming-Hao Pang Pei-Pei Yang Lu-Ming Guo Kuo Zhang Da-Yong Hou Lei Wang Hao Wang Hui Cao State key laboratory for Advanced Metals and Materials School of Materials Science and EngineeringUniversity of Science and Technology BeijingBeijing 100083China CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials NanosafetyNational Center for Nanoscience and Technology(NCNST)Beijing 100190China

Peptide drugs are known for their high biological ***,compared with small molecule drugs,peptide drugs are easily oxidized and hydrolyzed as well as short in ***,inspired by the long circulation of albumin in blood,we screened albumin binding peptides(ABPs)from a one-bead one-compound(OBOC)peptide library to increase the half-life of peptide *** displaying random peptides were screened using fluorescent labeled human serum *** beads with specific binding to albumin were isolated for *** selected ABPs can effectively bind to albumin,thus possessing the long circulation of *** dissociation constant(K_(D))of ABPs to albumin is up to 1×10^(-8)mol/*** one of ABPs(ABP2)was coupled to triptorelin,the circulation half-life of triptorelin in mice was significantly prolonged to 263.50 h much longer than that of triptorelin alone(179.07 h).In addition,the combination therapy using ABP-conjugated triptorelin and doxorubicin(DOX)can effectively inhibit the proliferation of tumor cells in *** OBOC screening strategy and resulting ABPs showed great potential for enhancing the delivery efficiency of peptide drugs.

关键词： One-bead one-compound Combinatorial library Albumin binding Drug delivery Triptorelin

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Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer

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National Science Review 2024年第4期11卷 216-227页

作者： Da-Yong Hou Ni-Yuan Zhang Lu Wang Mei-Yu Lv Xiang-Peng Li Peng Zhang Yue-Ze Wang Lei Shen Xiu-Hai Wu Bo Fu Peng-Yu Guo Zi-Qi Wang Dong-Bing Cheng Hao Wang Wanhai Xu NHC and CAMS key laboratory of Molecular Probe and Targeted Theranostics Heilongjiang Key Laboratory of Scientific Research in Urology Harbin Medical University Department of Urology Harbin Medical University Cancer Hospital CAS key laboratory for biomedical effects of nanomaterials and nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST) School of Chemistry Chemical Engineering & Life Science Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases Wuhan University of Technology

Mitochondriopathy inspired adenosine triphosphate(ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration(IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites,leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like ***, the reported transformable nucleopeptide(NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei,which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines(T24,EJ and RT-112) revealed that the half-maximal inhibitory concentration(IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.

关键词： self-assembly nucleopeptide nanomaterial bladder cancer mitochondriopathy

The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells

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Science China(Life Sciences) 2024年第9期67卷 1867-1880页

作者： Weixiao Yan Xiaotong Wang Wenjing Wang Qi Guo Na Huang Hao Chen Xing-Jie Liang Yu Han Dandan Liu Jinchao Zhang State key laboratory of New Pharmaceutical Preparations and Excipients/key laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education/College of Chemistry and Materials Science Chemical Biology Key Laboratory of Hebei ProvinceHebei UniversityBaoding 071002China CAS key laboratory for Biological effects of nanomaterials and nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Cancer stem cells(CSCs)play an important role in metastasis development,tumor recurrence,and treatment resistance,and are essential for the eradication of ***,therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape,which leads to enhanced aggressive behaviors compared with CSCs that have never been ***,the underlying mechanisms regulating the therapeutic escape remain *** this end,we established a model to isolate the therapeutic escaped CSCs(TSCSCs)from breast CSCs and performed the transcription profile to reveal the ***,we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway,resulting in TSCSCs exhibiting enhanced motility and ***,blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo,which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition(EMT)-related proteins vimentin and *** obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

关键词： therapeutic escape breast cancer stem cells motility p38/MAPK signaling pathway molecular mechanism

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Nanotechnology-based Detection Strategies for Hypertension Biomarkers

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Chemical Research in Chinese Universities 2024年第4期40卷 564-576页

作者： WANG Zhichao ZENG Yuan WANG Yaling CHEN Chunying Henan Institute of Advanced Technology Zhengzhou UniversityZhengzhou450003P.R.China CAS key laboratory for biomedical effects of nanomaterials and nanosafety&CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of ChinaChinese Academy of Sciences(CAS)Beijing100190P.R.China

Hypertension significantly increases the risk of cardiovascular diseases and seriously affects people’s *** incidence of hypertension is rising rapidly in the world and hypertension has become a significant factor influencing the global average life *** diagnosis of hypertension is generally fulfilled by measuring diastolic and systolic blood pressure,but it is insufficient to differentiate essential hypertension from secondary hypertension,so it is crucial to identifying the cause of hypertension by detecting biomarkers in *** clinical practice,five plasma biomarkers are utilized for diagnosing hypertension,and the detection tasks of a large number of cases have raised increasing demands for cost-effective,efficient,speedy,and diverse methods,which makes many traditional diagnostic technologies inadequate for meeting the needs of clinical *** nanomaterial-based detection techniques have frequently attained the qualities of quick reaction,low cost,straightforward operation,high sensitivity,and strong specificity in recent years with the advancement of nanotechnology,so they have great potential for early and rapid *** this review,we will introduce the characteristics and drawbacks of current clinical detection methods for hypertension screening,the principles and advancements of nanotechnology-based detection methods,as well as their potentials for clinical application.

关键词： Hypertension Biomarker Diagnosis Clinical detection Nanotechnology-based detection

Durable and enhanced immunity against SARS-CoV-2 elicited by manganese nanoadjuvant formulated subunit vaccine

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Signal Transduction and Targeted Therapy 2024年第1期9卷 47-50页

作者： Mengyu Guo Mingjing Cao Jiufeng Sun Ziwei Chen Xin Wang Lianpan Dai George F.Gao Yuliang Zhao Yaling Wang Chunying Chen CAS key laboratory for biomedical effects of nanomaterials and nanosafety&CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of ChinaBeijingChina Guangdong Provincial Institute of Public Health Guangdong Provincial Center for Disease Control and PreventionGuangzhouChina CAS key laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyBeijingChina

Dear editor,Vaccines are the most efficient and effective means to prevent infectious diseases,but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development.1 The waning immunity varies depending on the diversification of the pathogen and the number of booster doses.1 Strategies to overcome this warrant is using adjuvants that amplify the immune response,and drive the production of memory B and T cells or long-lived plasma cells that recognize the pathogen for durable protection.2–4 Although existing adjuvants have achieved promising results,research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of global pandemics such as coronavirus disease 2019(COVID-19).The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigenpresenting cell(APCs)uptake,achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses.5 Previously,we reported a manganese nanoadjuvant(MnARK)and receptor-binding domain(RBD)monomer antigen formulated nanovaccine.6 MnARK transported antigens to lymph nodes,activated the STING pathway,elicited strong neutralizing abilities and increased immune memory T cell percentage against the infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).6 Regarding the long-term protection potential of MnARK for subunit vaccine development,we further explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 RBD dimer antigen,which has been used in an approved COVID-19 subunit vaccine ZF2001 with aluminum adjuvant(alum).7,8 TEM result revealed that RBD dimer could interact with BSA on MnARK surface and epitope can be well preserved(Supplementary Fig.1a).The size and zeta potential of MnARK-RBD dimer nanovaccine was~58 nm and-14 mV,respectively(Supplementary Fig.1b,c).

关键词： manganese immunity protective

Silicon dioxide-protection boosting the peroxidase-like activity of Fe single-atom catalyst for combining chemo-photothermal therapy

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Nano Research 2024年第6期17卷 4924-4933页

作者： Yu Fan Yu Yi Hongpan Rong Jiatao Zhang Beijing key laboratory of Construction-Tailorable Advanced Functional Materials and Green Applications School of Materials Science&EngineeringBeijing Institute of TechnologyBeijing 100081China CAS Center for Excellence in Nanoscience CAS KeyLaboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and Technology(NCNST)Beijing 100190China key laboratory of Medical Molecule Science and Pharmaceutics Engineering Ministry of Industry and Information TechnologySchool of Chemistry&Chemical EngineeringBeijing Key Laboratory of Construction-Tailorable Advanced Functional Materials and Green ApplicationsSchool of Materials Science and EngineeringBeijing Institute of TechnologyBeijing 100081China

Carbon-based single-atom catalysts(SACs)have been widely studied in the field of biomedicine due to their excellent catalytic ***,carbon-based SACs usually aggregate during pyrolysis,which leads to the reduction of catalytic ***,we describe a method to improve the monodispersion of SACs using silicon dioxide as a protective *** decoration of silicon dioxide serves as a buffer layer for individual nanoparticles,which is not destroyed during the pyrolysis process,ensuring the single-particle dispersion of the nanoparticles after *** approach increased the hydroxyl groups on the surface of Fe-SAC(Fe-SAC-SE)and improved its water solubility,resulting in a four times enhancement of the peroxidase(POD)-like activity of Fe-SAC-SE(58.4 U/mg)than that of non-protected SACs(13.9 U/mg).The SiO_(2)-protection approach could also improve the catalytic activities of SACs with other metals such as Mn,Co,Ni,and Cu,indicating its generality for SACs *** advantage of the high POD-like activity,photothermal properties,and large specific surface area of Fe-SAC-SE,we constructed a synergistic therapeutic system(Fe-SAC-SE@DOX@PEG)for combining the photothermal therapy,catalytic therapy,and *** was verified that the photothermal properties of Fe-SAC-SE@DOX@PEG could effectively improve its POD-like activity,exhibiting excellent tumor-killing performance at the cellular *** work may provide a general approach to improve the performances of SACs for disease therapy and diagnosis.

关键词： single-atom catalysts peroxidase-like activity SiO2-protection photothermal therapy catalytic therapy chemotherapy

pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 781-794页

作者： Shuai Guo Chunhui Li Changrong Wang Xiaowen Cao Xinyue Liu Xing-Jie Liang Yuanyu Huang Yuhua Weng School of Medical Technology Advanced Research Institute of Multidisciplinary ScienceSchool of Life ScienceKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China School of Pharmacy Shandong New Drug Loading&Release Technology and Preparation Engineering LaboratoryBinzhou Medical UniversityYantai 264003China School of Ophthalmology and Optometry School of Biomedical EngineeringThe Eye HospitalWenzhou Medical UniversityWenzhou 325027China Chinese Academy of Sciences(CAS) Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China

Small interfering RNA(siRNA)has a promising future in the treatment of ocular diseases due to its high efficiency,specificity,and low toxicity in inhibiting the expression of target genes and ***,due to the unique anatomical structure of the eye and various barriers,delivering nucleic acids to the retina remains a significant *** this study,we rationally design PACD,an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block(A),a siRNA binding block(B)and a pH-responsive block(C).PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple *** evaluating its pH-responsive activity,gene silencing efficiency in retinal cells,intraocular distribution,and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis,we demonstrate the efficiency and safety of PACD in delivering siRNA in the *** are surprised to discover that,the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency,excellent gene silencing,and inhibit retinal *** study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

关键词： SiRNA Oculardeliverysystem Block polymer Endosomalescape Retinal neovascularization Blood-retinal barrier VEGFA Safety

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Biomaterial design for regenerating aged bone:materiobiological advances and paradigmatic shifts

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National Science Review 2024年第5期11卷 405-419页

作者：戴凯耿振张文超魏雪王靖聂广军刘昌胜 Engineering Research Center for biomedical Materials of the Ministry of Education East China University of Science and Technology State key laboratory of Bioreactor Engineering East China University of Science and Technology Frontiers Science Center for Materiobiology and Dynamic Chemistry East China University of Science and Technology key laboratory for Ultrafine Materials of the Ministry of Education East China University of Science and Technology Institute of Translational Medicine Shanghai University National Center for Translational Medicine(Shanghai) SHU Branch Shanghai University CAS key laboratory for biomedical effects of nanomaterials &nanosafety CAS Centre for Excellence in Nanoscience National Centre for Nanoscience and Technology Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences

China's aging demographic poses a challenge for treating prevalent bone diseases impacting life quality. As bone regeneration capacity diminishes with age due to cellular dysfunction and inflammation, advanced biomaterials-based approaches offer hope for aged bone regeneration. This review synthesizes materiobiology principles, focusing on biomaterials that target specific biological functions to restore tissue integrity. It covers strategies for stem cell manipulation, regulation of the inflammatory microenvironment,blood vessel regeneration, intervention in bone anabolism and catabolism, and nerve regulation. The review also explores molecular and cellular mechanisms underlying aged bone regeneration and proposes a database-driven design process for future biomaterial development. These insights may also guide therapies for other age-related conditions, contributing to the pursuit of ‘healthy aging'.

关键词： materiobiology biomaterial design aging bone regeneration artificial intelligence