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Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis

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Chinese Medical Journal 2023年第23期136卷 2787-2801页

作者： Lingling Zhu Juan Wu Honglin Gao Ting Wang Guixiu Xiao Chenggong Hu Qing Lin Qinghua Zhou Lung Cancer Center Lung Cancer InstituteWest China Hospital of Sichuan UniversityChengduSichuan 610041China Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacyCollege of Polymer Science and EngineeringSichuan UniversityChengduSichuan 610041China Out-patient Department West China HospitalSichuan UniversityChengduSichuan 610041China Department of Critical Care Medicine West China Hospital of Sichuan UniversityChengduSichuan 610041China

As one of the most malignant tumors worldwide,lung cancer,fueled by metastasis,has shown rising mortality rates.However,effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step,complicated,and progressive nature.Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment.However,drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response.Consequently,adverse effects occur,such as autoimmunity,from the non-specific immune activation and non-specific inflammation in off-target organs.Nanocarriers that improve drug solubility,permeability,stability,bioavailability,as well as sustained,controlled,and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects.In particular,nanomedicine-based immunotherapy can be utilized to target tumor metastasis,presenting a promising therapeutic strategy for lung cancer.Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment;the breaking away of primary tumors,circulating tumor cell dissemination,and premetastatic niche formation cause distant secondary site colonization.In this review,we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer.We also discuss prospects for the emerging field and the clinical translation potential of these techniques.

关键词： nanomedicine Lung cancer Metastasis Immunotherapy Tumor microenvironment

An antioxidant system through conjugating superoxide dismutase onto metal-organic framework for cardiac repair

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Bioactive Materials 2022年第4期7卷 56-67页

作者： Jiacheng Guo Zhenzhen Yang Yongzheng Lu Chunyan Du Chang Cao Bo Wang Xiaoting Yue Zenglei Zhang Yanyan Xu Zhen Qin Tingting Huang Wei Wang Wei Jiang Jinying Zhang Junnan Tang Department of Cardiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Key Laboratory of Cardiac Injury and Repair of Henan Province ZhengzhouHenan450018China Department of Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Laboratory Animal Center School of Medical SciencesZhengzhou UniversityZhengzhouHenan450052China Department of Polymer Science College of ChemistryJilin UniversityChangchunJilin130012China Henan Medical Association ZhengzhouHenan450052China Academy of Medical Science Zhengzhou UniversityZhengzhouHenan450052China

Acute myocardial infarction(AMI)remains a dominant origin of morbidity,mortality and disability worldwide.Increases in reactive oxygen species(ROS)are key contributor to excessive cardiac injury after AMI.Here we developed an immobilized enzyme with Superoxide Dismutase(SOD)activity cross-link with Zr-based metal-organic framework(ZrMOF)(SOD-ZrMOF)for mitigate ROS-caused injury.In vitro and in vivo evidence indicates that SOD-ZrMOF exhibits excellent biocompatibility.By efficiently scavenging ROS and suppressing oxidative stress,SOD-ZrMOF can protect the function of mitochondria,reduce cell death and alleviate inflammation.More excitingly,long-term study using an animal model of AMI demonstrated that SOD-ZrMOF can reduce the infarct area,protect cardiac function,promote angiogenesis and inhibit pathological myocardial remodeling.Therefore,SOD-ZrMOF holds great potential as an efficacious and safe nanomaterial treatment for AMI.

关键词： Acute myocardial infarction Immobilized enzyme Reactive oxygen species nanomedicine

Nanoemulsions for drug delivery

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Particuology 2022年第5期20卷 85-97页

作者： Russell J.Wilson Yang Li Guangze Yang Chun-Xia Zhao Australian Institute for Bioengineering and Nanotechnology The University of QueenslandSt Lucia Queensland 4072Australia

Emulsions are liquid-liquid dispersions with one liquid phase dispersed in the other liquid phase as small droplets.Nanoemulsions are nano-sized emulsions with sizes ranging from tens to hundreds of nanometers,and have great potential applications in pharmaceutics,foods and cosmetics due to their attractive properties,such as small sizes,high surface area per unit volume,improved dispersion of active hydrophobic components and enhanced absorption.The article provides an overview of nanoemulsions for drug delivery,starting with an introduction of emulsion types,nanoemulsion preparation and nanoemulsion stability.Surfactants play critical roles in producing and stabilizing nanoemulsions.Different types of surfactants are summarized including small molecule surfactants,particle surfactants,phospholipids,peptide and protein surfactants.Then the applications of nanoemulsions as nanomedicine in drug delivery are presented.Finally,clinical applications of nanoemulsions are discussed.

关键词： Nanoemulsions Surfactants Drug delivery nanomedicine Peptide surfactant

Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis

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Bioactive Materials 2022年第8期7卷 250-261页

作者： Liming Zheng Zaikai Zhuang Yixuan Li Tianshu Shi Kai Fu Wenjin Yan Lei Zhang Peng Wang Lan Li Qing Jiang State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical School321 Zhongshan RoadNanjing210008JiangsuPR China Branch of National Clinical Research Center for Orthopedics Sports Medicine and RehabilitationPR China Jiangsu Engineering Research Center for 3D Bioprinting Nanjing210008PR China

Osteoporosis is the most common degenerative orthopedic disease in the elderly.Recently,the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues,which could provide a suitable environment for the positive regulation of bone metabolism,promoting osteogenic differentiation and inhibiting osteoclast differentiation.Our previous work demonstrated that iron oxide nanoparticles(IONPs)could positively regulate bone metabolism in vitro.In this study,we further demonstrated that daily administration of IONPs relieved estrogen deficiency-induced osteoporosis via scavenging reactive oxygen species in vivo.Meanwhile,IONPs promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited the osteoclast differentiation of monocytes from IONPs treated mice.Besides,alendronate,a clinically used anti-osteoporosis bisphosphate,was employed to precisely deliver the IONPs to the bone tissues and played a synergically therapeutic role.Eventually,we verified the bone targeting ability,therapeutic efficiency,and biocompatibility of the novel bone target iron oxides in ovariectomy-induced osteoporotic mice.By applying BTNPs,the OVX-induced osteoporosis was significantly revised in mice models via the positive regulation of bone metabolism.

关键词： Osteoporosis Bone targeting Iron oxide Antioxidant nanomedicine

2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy

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Bioactive Materials 2022年第8期7卷 76-85页

作者： Yunjie Xu Yingwei Wang Jusung An Adam C.Sedgwick Mingle Li Jianlei Xie Weibin Hu Jianlong Kang Sajal Sen Axel Steinbrueck Bin Zhang Lijun Qiao Swelm Wageh Jonathan F.Arambula Liping Liu Han Zhang Jonathan L.Sessler Jong Seung Kim Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of EducationShenzhen Institute of Translational MedicineDepartment of OtolaryngologyShenzhen Second People’s HospitalThe First Affiliated HospitalCollege of Optoelectronic EngineeringShenzhen UniversityShenzhen518060China Department of Chemistry Korea UniversitySeoul02841South Korea Department of Hepatobiliary and Pancreatic Surgery Shenzhen People’s HospitalSecond Clinical Medical College of Jinan UniversityShenzhen518020China Department of Chemistry The University of Texas at AustinAustinTX78712-1224USA Hunan Key Laboratory of Nanophotonics and Devices School of Physics and ElectronicsCentral South University932 South Lushan RoadChangsha410083China Institute of Translation Medicine Shenzhen Second People’s Hospital First Affiliated Hospital of Shenzhen University Shenzhen518035China Department of Physics Faculty of ScienceKing Abdulaziz UniversityJeddah21589Saudi Arabia

An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfortunately,current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities.We report here a dual-therapeutic prodrug,DOXjade,that allows for iron chelation chemo-photothermal cancer therapy.This prodrug takes advantage of the clinically approved iron chelator deferasirox(ExJade®)and the topoisomerase 2 inhibitor,doxorubicin(DOX).Loading DOXjade onto ultrathin 2D Ti_(3)C_(2) MXene nanosheets produces a construct,Ti_(3)C_(2)-PVP@DOXjade,that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites,while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%.Antitumor mechanistic investigations reveal that upon activation,Ti_(3)C_(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor(TfR).A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo.The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.

关键词： 2D MXene nanomedicine Prodrug Iron chelation Photothermal therapy

Exosome-mediated aptamer S58 reduces fibrosis in a rat glaucoma filtration surgery model

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International Journal of Ophthalmology(English edition) 2022年第5期15卷 690-700页

作者： Qian-Yi Lin Xiang-Ji Li Yu Leng Xiao-Min Zhu Min Tang Yi Lin Wang-Du Luo Bing-Cai Jiang Xia Chen Lin Xie Department of Ophthalmology The Third Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Ophthalmology Daping Hospital of Army Medical UniversityChongqingChina

AIM:To confirm whether exosome-mediated delivery of aptamer S58(Exo-S58) has a better antifibrotic effect than naked S58 in human conjunctival fibroblasts(HCon Fs) and a rat glaucoma filtration surgery(GFS) model.METHODS:To enhance the effective reaction time of aptamer S58 in vivo, we loaded aptamer S58 into exosomes derived from HEK293 T cells by PEI transfection to determine the effect of Exo-S58 in HCon Fs and a rat GFS model.RESULTS:Exo-S58 can significantly reduce cell proliferation, migration and fibrosis in TGF-β2-induced HCon Fs. In an in vivo experiment, Exo-S58 treatment prolonged filtering bleb retention and reduced fibrosis compared with naked S58 treatment in GFS rats.CONCLUSION:The exosomes are safe and valid carriers to deliver aptamers. Furthermore, Exo-S58 exhibited superior antifibrotic effect than naked S58 both in HCon Fs cells and rat GFS models.

关键词： nanomedicine exosomes aptamer drug delivery glaucoma surgery transforming growth factor-beta anti-fibrosis

Spectral computed tomography-guided photothermal therapy of osteosarcoma by bismuth sulfide nanorods

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Nano Research 2023年第7期16卷 9885-9893页

作者： Yuhan Li Xiaoxue Tan Han Wang Xiuru Ji Zi Fu Kai Zhang Weijie Su Jian Zhang Dalong Ni School of Medicine Shanghai UniversityNo.99 Shangda RdShanghai 200444China Shanghai University Shanghai Universal Medical Imaging Diagnostic CenterBldg 8No.406 Guilin RdShanghai 200233China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineNo.197Ruijin 2nd RdShanghai 200025China Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai JiaoTong University School of MedicineNo.639Zhizaoju Rd.Shanghai 200011China

Osteosarcoma(OS)is the most normally primary malignant bone cancer in adolescents.Due to their analogous X-ray attenuation properties,healthy bones and malignancies with iodine enhancement cannot be distinguished by conventional computed tomography(CT).As one kind of spectral CT,dual-energy CT(DECT)offers multiple functions for material separation and cancer treatments.Herein,bismuth sulfide(Bi_(2)S_(3))nanorods(NRs)were synthesized as special contrast agents(CAs)for DECT,which have superior imaging properties than clinical iodine CAs.At the same time,the high photothermal conversion rates of Bi_(2)S_(3)NRs can be used for DECT-guided photothermal therapy(PTT)to destroy OS and inhibit tumor growth under the guidance of DECT imaging.Importantly,DECT imaging real-timely monitored that PTT could accelerate the diffusion of Bi2S3 NRs in the tumor,obtaining detailed information on the internal distribution of nanomaterials in tumors around the bone to avoid injury to normal tissues by PTT.Overall,the proposed strategy of DECT imaging-guided PTT appears enormous promise for bone disease treatment.

关键词： dual-energy computed tomography nanomedicine bismuth sulfide photothermal therapy osteosarcoma

Coordination-driven self-assembly of metallo-nanodrugs for local inflammation alleviation

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Nano Research 2023年第12期16卷 13259-13266页

作者： Lijuan Tang Zhenghan Di Jingfang Zhang Feiying Yin Lele Li Li Zheng Guangxi Key Laboratory of Regenerative Medicine Guangxi Engineering Center in Biomedical Material for Tissue and Organ RegenerationCollaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development nd Application Co-Constructed by the Province and MinistryThe First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Pharmaceutical College Guangxi Medical UniversityNanning 530021China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Developing dedicated nanomedicines to improve delivery efficacy of anti-inflammatory drugs is still a formidable challenge.In this study,we present an extremely simple yet efficient approach to obtain hybrid nanodrugs through metal-drug coordination-driven self-assembly for carrier-free drug delivery.The resulting metallo-nanodrugs exhibit well-defined morphology and high drug encapsulation capability,allowing for the combination of magnetic resonance imaging and anti-inflammatory therapy.In the case of osteoarthritis(OA),the metallo-nanodrugs remarkably alleviate synovial inflammation,preventing cartilage destruction and extracellular matrix loss.In addition,it led to significantly improved therapeutic efficacy compared with intra-articular administration of the same dose of free drugs in OA mouse model.This work provides a very simple approach for the development of anti-inflammatory nanoformulations by exploiting coordination-driven self-assembly.

关键词： drug delivery coordination-driven assembly nanomedicine anti-inflammation therapy

Ferroptosis:An emerging therapeutic opportunity for cancer

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Genes & Diseases 2022年第2期9卷 334-346页

作者： Liyuan Wang Xiaoguang Chen Chunhong Yan Georgia Cancer Center Augusta UniversityAugustaGA 30912USA Department of Pharmacology Institute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100050China Department of Pharmacy Peking University Third HospitalBeijing 100191China Department of Biochemistry and Molecular Biology Medical College of GeorgiaAugusta UniversityAugustaGA 30912USA

Ferroptosis,a new form of non-apoptotic,regulated cell death characterized by iron dependency and lipid peroxidation,is involved in many pathological conditions such as neurodegenerative diseases,heart ischemia/reperfusion injury,acute renal failure,and cancer.While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death,glutathione peroxidase 4(GPX4)resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation,thereby suppressing ferroptosis.Indeed,RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in mice.Similarly,erastin and other system Xc−inhibitors can deplete intracellular glutathione required for GPX4 function,leading to lipid peroxidation and ferroptosis.As therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens,the agents capable of inducing ferroptosis hold great promises to improve current cancer therapy.This review will outline the molecular basis of ferroptosis,but focus on the strategies and the agents developed in recent years for therapeutic induction of ferroptosis.The potentials of these ferroptosis-inducing agents,which include system Xc−inhibitors,GPX4 inhibitors,and iron-based nanoparticles,in cancer therapy will be subsequently discussed.

关键词： Cancer therapy Erastin Ferroptosis GPX4 Lipid peroxidation nanomedicine RSL3 System Xc-