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Legumain-triggered aggregable gold nanoparticles for enhanced intratumoral retention

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Chinese Chemical Letters 2024年第7期35卷 388-393页

作者： Zhi Li Wenpei Li Shaoping Jiang Chuan Hu yuanyu huang Maxim Shevtsov Huile Gao Shaobo Ruan Advanced Research Institute of Multidisciplinary Sciences School of Life ScienceBeijing Institute of TechnologyBeijing 100081China Key Laboratory of Drug Targeting and Drug Delivery System West China School of PharmacySichuan UniversityChengdu 610041China Institute of Cytology of Russian Academy of Sciences(RAS) St.Petersburg 194064Russia

Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical ***,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNPs-A&C).GNPs-A&C could form intratumoral or intracellular aggregates in response to the overexpressed *** aggregates with size increase not only could reduce back-flow from interstitial space to peripheral bloodstream but also could restrict the cellular exocytosis,leading to enhanced intratumoral *** vitro studies demonstrated that GNPs-A&C possessed an excellent legumain responsiveness and the increased size was closely relevant with legumain *** vivo studies demonstrated GNPs-A&C possessed slower clearance rate and much higher intratumoral retention within legumain-overexpressed tumor compared to non-aggregable NPs,regardless of intravenous or intratumoral *** importantly,this delivery platform significantly improved the chemotherapeutic effect of doxorubicin(DOX)towards subcutaneous xenograft C6 *** effectiveness of this stimulus-responsive aggregable delivery system provides a thinking for designing more intelligent size-tunable nanomedicine that can substantially improve intratumoral retention.

关键词： Legumain Size-tunable Enhanced retention Stimulus-responsive Nanomedicine

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

Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential ant1ip1 an-coronavirus activity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1186-1198页

作者： Minghui Yang Chunhui Li Guoguo Ye Chenguang Shen Huiping Shi Liping Zhong Yuxin Tian Mengyuan Zhao Pengfei Wu Abid Hussain Tian Zhang Haiyin Yang Jun Yang Yuhua Weng Xinyue Liu Zhimin Wang Lu Gan Qianyu Zhang Yingxia Liu Ge Yang yuanyu huang Yongxiang Zhao School of Life Science Advanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China National Clinical Research Center for infectious disease Shenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Targeting Oncology National Center for International Research of Biotargeting TheranosticsGuangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Medical UniversityNanning 530021China CAMS Key Laboratory of Antiviral Drug Research Beijing Key Laboratory of Antimicrobial AgentsInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health *** light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently ***,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 *** aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,*** protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

关键词： acute threat conclusion

mRNA-based modalities for infectious disease management

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Nano Research 2023年第1期16卷 672-691页

作者： Mengjie Zhang Abid Hussain Haiyin Yang Jinchao Zhang Xing-Jie Liang yuanyu huang School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical Technology(Institute of Engineering Medicine)Key Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China School of Materials and the Environment Beijing Institute of TechnologyZhuhai 519085China Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education College of Chemistry and Environmental ScienceHebei UniversityBaoding 071002China Chinese Academy of Sciences(CAS)Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and Technology of ChinaBeijing 100190China

The novel coronavirus disease 2019(COVID-19)is still rampant all over the world,causing incalculable losses to the *** pharmaceutical organizations around the globe are focusing on vaccine research and drug development to prevent further damage caused by the *** messenger RNA(mRNA)technology has got ample of attention after the success of the two very effective mRNA vaccines during the recent pandemic of *** vaccine has been promoted to the core stage of pharmaceutical industry,and the rapid development of mRNA technology has exceeded *** COVID-19,the mRNA vaccine has been tested for various infectious diseases and undergoing clinical *** to the ability of constant mutation,the viral infections demand abrupt responses and immediate production,and therefore mRNA-based technology offers best answers to sudden *** need for mRNA-based vaccine became more obvious due to the recent emergence of new Omicron *** this review,we summarized the unique properties of mRNA-based vaccines for infectious diseases,delivery technologies,discussed current challenges,and highlighted the prospects of this promising technology in the *** also discussed various clinical studies as well preclinical studies conducted on mRNA therapeutics for diverse infectious diseases.

关键词： messenger RNA(mRNA)vaccine lipid-nanoparticle infectious disease drug delivery coronavirus disease 2019(COVID-19) virus

Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles

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药学学报:英文版 2023年第9期13卷 3945-3955页

作者： Mei Lu Haonan Xing Wanxuan Shao Pengfei Wu Yuchuan Fan Huining He Stefan Barth Aiping Zheng Xing-Jie Liang yuanyu huang Advanced Research Institute of Multidisciplinary Science School of Life ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Chinese Academy of Sciences(CAS)Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China South African Research Chair in Cancer Biotechnology Institute of Infectious Disease and Molecular Medicine(IDM)Department of Integrative Biomedical SciencesFaculty of Health SciencesUniversity of Cape TownCape Town 7925South Africa

Immunotherapy has revolutionized the landscape of cancer ***,single immunotherapy only works well in a small subset of *** immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic ***,the synergistic,additive or antagonistic antitumor effects of combined immunotherapies have been rarely ***,we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4(PAK4)silencing with immunogenic phototherapy in engineered extracellular vesicles(EVs)that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with si RNA against PAK4 and a photoactivatable *** engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy,thus contributing to effective antitumor effects in vitro and in ***,the antitumor synergism of the combined treatment was quantitatively determined by the Compu Syn *** combination index(CI)and isobologram results confirmed that there was an antitumor synergism for the combined ***,the dose reduction index(DRI)showed favorable dose reduction,revealing lower toxicity and higher biocompatibility of the engineered ***,the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs,which is promising for boosting the therapeutic outcome of cancer immunotherapy.

关键词： Antitumor synergism Combined cancer immunotherapy p21-activated kinase 4 RNA interference Immunogenic phototherapy Extracellular vesicles Immune infiltration CompuSyn

siRNA-functionalized lanthanide nanoparticle enables efficient endosomal escape and cancer treatment

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Nano Research 2022年第10期15卷 9160-9168页

作者： Chanchan Yu Kun Li Lin Xu Bo Li Chunhui Li Shuai Guo Ziyue Li Yuquan Zhang Abid Hussain Hong Tan Mengyu Zhang Yongxiang Zhao yuanyu huang Xing-Jie Liang School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical Technology(Institute of Engineering Medicine)Key Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China National Center for International Research of Biological Targeting Diagnosis and Therapy Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy ResearchGuangxi Medical UniversityNanning 530021China

Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug ***,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaGdF4 NPs),and forms siRNA/NaGdF4 spherical nucleic acids(SNA).The coordination is primarily attributed to the interaction between Gd and phosphate backbone of the ***,an efficient encapsulation and rapid endosomal escape of siRNA from the endosome/lysosome were achieved,due to its flexible ability to bound to phospholipid head of endosomal membrane,thereby disrupting the membrane *** to the dual properties of NaGdF4 NPs,siRNA loading,and endosomal escape,siRNA targeting programmed cell death-ligand 1(siPD-L1)/NaGdF4 SNA triggers significant gene silencing in vitro and in vivo,and effectively represses the tumor growth in both CT26 tumor model and 4T1 orthotopic murine model.

关键词： coordination chemistry nuclei acid lanthanide nanomaterials small interfering RNA(siRNA)delivery endosome escape

Biosafety materials:Ushering in a new era of infectious disease diagnosis and treatment with the CRISPR/Cas system

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Biosafety and Health 2022年第2期4卷 70-78页

作者： Yuquan Zhang Ziyue Li Julien Milon Essola Kun Ge Xuyan Dai Huining He Haihua Xiao Yuhua Weng yuanyu huang School of Life Science School of Medical TechnologyAdvanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Key Laboratory of Analytical Science and Technology of Hebei Province College of Chemistry and Environmental ScienceKey Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of EducationHebei UniversityBaoding 071000China Hunan Agricultural University Changsha 410128China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Beijing National Laboratory for Molecular Science State Key Laboratory of Polymer Physical and ChemistryInstitute of ChemistryChinese Academy of ScienceBeijing 100190China School of Materials and the Environment Beijing Institute of TechnologyZhuhai 519085China

Despite multiple virus outbreaks over the past decade,including the devastating coronavirus disease 2019(COVID-19)pandemic,the lack of accurate and timely diagnosis and treatment technologies has wreaked havoc on global *** clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)system has the potential to address these critical needs for tackling infectious diseases to detect viral nucleic acids and inhibit viral *** review summarizes how the CRISPR/Cas system is being utilized for the treatment and diagnosis of infectious diseases with the help of biosafety materials and highlights the design principle and in vivo and in vitro efficacy of advanced biosafety materials used to deal with virus attacks.

关键词： Biosafety materials CRISPR/Cas SARS-CoV-2 Diagnosis Infectious disease

Ionizable liposomal siRNA therapeutics enables potent and persistent treatment of Hepatitis B

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Signal Transduction and Targeted Therapy 2022年第3期7卷 802-815页

作者： yuanyu huang Shuquan Zheng Zhaoxu Guo Xavier de Mollerat du Jeu Xing-Jie Liang Zhiwei Yang Hong-Yan Zhang Shan Gao Zicai Liang Suzhou Ribo Life Science Co.Ltd. Jiangsu 215300China Advanced Research Institute of Multidisciplinary Science School of Life ScienceSchool of Medical Technology(Institute of Engineering Medicine)Key Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Thermo Fisher Scientific CarlsbadCAUSA Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Chinese Academy of Sciences(CAS)National Center for Nanoscience and TechnologyBeijing 100190China

Small interfering RNA(siRNA)constitutes a promising therapeutic modality supporting the potential functional cure of hepatitis B.A novel ionizable lipidoid nanoparticle(RBP131)and a state-of-the-art lyophilization technology were developed in this study,enabling to deliver siRNA targeting apolipoprotein B(APOB)into the hepatocytes with an ED_(50)of 0.05 mg/kg after intravenous *** addition,according to the requirements of Investigational New Drug(IND)application,a potent siRNA targeting hepatitis B virus(HBV)was selected and encapsulated with RBP131 to fabricate a therapeutic formulation termed RB-HBV008.

关键词： injection APOB intravenous

Recent advances in photothermal and RNA interfering synergistic therapy

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Chinese Chemical Letters 2021年第3期32卷 1010-1016页

作者： Kun Li Mei Lu Xinhua Xia yuanyu huang School of Life Science Advanced Research Institute of Multidisciplinary ScienceInstitute of Engineering MedicineKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China School of Pharmacy Hunan University of Chinese MedicineChangsha 410208China

As a new treatment technique,photothermal therapy(PTT)has aroused worldwide attention in cancer treatment,mainly due to its excellent absorption ability,easy regulation,and *** conversion materials with enhanced permeability and retention effect can be targeted easily to tumor *** can accumulate efficiently to tumor tissues and allow normal tissues and organs not to be affected by temperature,thus significantly helping to reduce the systemic toxicity and improve the antitumor ***,PTT alo ne often suffers from the rapeutic resistance and reduced therapeutic efficacy,due to photothermal nanomaterial-mediated fundamental cellular defense mechanism of heat shock response,which could be inhibited by small interfering RNA(siRNA).Nevertheless,photothermal conversion materials as an excellent siRNA delivery carrier may conside rably enhance the delivery efficiency of ***,photothermal and RNA interfering(RNAi)synergistic therapy has recently aroused extensive attention in tumor *** this review,we mainly summarize the recent advances of photothermal and RNAi synergistic therapy,including some synergistic therapeutic nanoplatforms of inorganic and organic photothermal materials and other combined therapies such as combining with small molecular antitumor agents or PDT/*** combination of various treatment techniques may considerably improve the synergistic therapeutic effect of PTT and RNAi in the treatment of cancers.

关键词： Photothermal therapy RNAi RNA interference siRNA Small interfering RNA Gold nanoparticle Carbon nanoparticle