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photothermal therapy with regulated Nrf2/NF-κB signaling pathway for treating bacteria-induced periodontitis

Bioactive Materials 2022年第3期7卷 428-445页

作者： Yujuan Tian Ying Li Jialin Liu Yi Lin Jian Jiao Bo Chen Wanmeng Wang Shuilin Wu Changyi Li School of Dentistry Stomatological HospitalTianjin Medical UniversityTianjin300070People’s Republic of China School of Materials Science&Engineering Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of ChinaTianjin UniversityTianjin300072People’s Republic of China

Periodontitis is an inflammatory disease initiated by bacterial infection,developed by excessive immune response,and aggravated by high level of reactive oxygen species(ROS).Hence,herein,a versatile metal-organic framework(MOF)-based nanoplatform is prepared using mesoporous Prussian blue(MPB)nanoparticles to load BA,denoted as MPB-BA.The established MPB-BA nanoplatform serves as a shelter and reservoir for vulnerable immunomodulatory drug BA,which possesses antioxidant,anti-inflammatory and anti-bacterial effects.Thus,MPB-BA can exert its antioxidant,anti-inflammatory functions through scavenging intracellular ROS to switch macrophages from M1 to M2 phenotype so as to relieve inflammation.The underlying molecular mechanism lies in the upregulation of phosphorylated nuclear factor erythroid 2-related factor 2(Nrf2)to scavenge ROS and subsequently inhibit the nuclear factor kappa-B(NF-κB)signal pathway.Moreover,MPB-BA also exhibited efficient photothermal antibacterial activity against periodontal pathogens under near-infrared(NIR)light irradiation.In vivo RNA sequencing results revealed the high involvement of both antioxidant and anti-inflammatory pathways after MPB-BA application.Meanwhile,micro-CT and immunohistochemical staining of p-Nrf2 and p-P65 further confirmed the superior therapeutic effects of MPB-BA than minocycline hydrochloride.This work may provide an insight into the treatment of periodontitis by regulating Nrf2/NF-κB signaling pathway through photothermal bioplatform-assisted immunotherapy.

关键词： Periodontitis Prussian blue photothermal therapy Nrf2/NF-κB signaling pathway Bacterial infection

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CD137 agonist potentiates the abscopal efficacy of nanoparticle-based photothermal therapy for melanoma

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Nano Research 2022年第3期15卷 2300-2314页

作者： Preethi Bala Balakrishnan Debbie KLedezma Juliana Cano-Mejia Jaclyn Andricovich Erica Palmer Vishal APatel Patricia SLatham Eric SYvon Alejandro Villagra Rohan Fernandes Elizabeth E.Sweeney GW Cancer Center Department of MedicineSchool of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20052USA The Institute for Biomedical Sciences School of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20052USA GW Cancer Center Department of Biochemistry and Molecular MedicineSchool of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20052USA Department of Dermatology&Oncology School of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20037USA Department of Pathology School of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20037USA ImmunoBlue BethesdaMD 20817USA

Despite the promise of immunotherapy such as the immune checkpoint inhibitors(ICIs)anti-PD-1 and anti-CTLA-4 for advanced melanoma,only 26%–52%of patients respond,and many experience grade III/IV immune-related adverse events.Motivated by the need for an effective therapy for patients non-responsive to clinically approved ICIs,we have developed a novel nanoimmunotherapy that combines locally administered Prussian blue nanoparticle-based photothermal therapy(PBNP-PTT)with systemically administered agonistic anti-CD137 monoclonal antibody therapy(aCD137).PBNP-PTT was administered at various thermal doses to melanoma cells in vitro,and was combined with aCD137 in vivo to test treatment effects on melanoma tumor progression,animal survival,immunological protection against tumor rechallenge,and hepatotoxicity.When administered at a melanoma-specific thermal dose,PBNP-PTT elicits immunogenic cell death(ICD)in melanoma cells and upregulates markers associated with antigen presentation and immune cell co-stimulation in vitro.Consequently,PBNP-PTT eliminates primary melanoma tumors in vivo,yielding long-term tumor-free survival.However,the antitumor immune effects generated by PBNP-PTT cannot eliminate secondary tumors,despite significantly slowing their growth.The addition of aCD137 enables significant abscopal efficacy and improvement of survival,functioning through activated dendritic cells and tumor-infiltrating CD8^(+)T cells,and generates CD4^(+)and CD8^(+)T cell memory that manifests in the rejection of tumor rechallenge,with no long-term hepatotoxicity.This study describes for the first time a novel and effective nanoimmunotherapy combination of PBNP-PTT with aCD137 mAb therapy for melanoma.

关键词： photothermal therapy Prussian blue nanoparticles anti-CD137 melanoma nanoimmunotherapy

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Pd@Ir-LOD multienzyme utilizing endogenous lactate consumption cooperates with photothermal for tumor therapy

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Nano Research 2024年第1期17卷 270-281页

作者： Zichen Ye Yun Li Jingchao Li Xinyan Hu Jinyang Zheng Gongxin Zhang Sijin Xiang Tianbao Zhu Zhide Guo Xiaolan Chen State Key Laboratory for Physical Chemistry of Solid Surfaces Collaborative Innovation Center of Chemistry for Energy Materials and Engineering Research Center for Nano-Preparation Technology of Fujian ProvinceCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics&Center for Molecular Imaging and Translational Medicine School of Public Health Xiamen UniversityXiamen 361102China The High Educational Key Laboratory for Biomedical Engineering&Key Laboratory of Fire Retardant Materials of Fujian Province Department of BiomaterialsCollege of MaterialsXiamen UniversityXiamen 361102China

Lactic acid(LA)plays a major role in the occurrence,development,and spread of cancer.Enlightened by its high accumulation in tumor site,a novel lactate oxidase(LOD)conjugated two-dimensional Pd@Ir nanoplatform(Pd@Ir-LOD,PIL)was fabricated to combine cascade reaction with photothermal for tumor therapy.In detail,the overexpressed LA in tumor microenvironment(TME)was a key factor to activate the PIL-based cascade reaction:(1)Plenty of H_(2)O_(2)could be generated from LA by the catalysis of LOD with O_(2);(2)potent·OH was produced from H_(2)O_(2)due to the peroxidase(POD)-like activity of PIL;(3)meantime,PIL’s catalase(CAT)-like activity could decompose part H_(2)O_(2)into O_(2)to achieve the purpose of LA cyclic oxidization.Moreover,the reduced glutathione(GSH)scavenging capability of PIL might protect the produced reactive oxygen species(ROS)from being cleared to further improve the cascade therapeutic effect.More importantly,PIL had excellent photothermal conversion efficiency(37.35%)and manifested a surprising temperature rising effect in tumor.Taken together,the decreasing LA concentration,accumulation of high-toxic ROS,the depletion of GSH together with the higher intra-tumoral temperature potently enhanced in vivo antitumor therapy.Therefore,a promising therapeutic tactic based on PIL integrating endogenous LA consumption,chemodynamic therapy(CDT),and photothermal therapy(PTT)has been put forward.

关键词： lactate oxidase chemodynamic therapy photothermal therapy cascade reaction tumor microenvironment

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Bilayer hydrogel dressing with lysozymeenhanced photothermal therapy for biofilm eradication and accelerated chronic wound repair

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Acta Pharmaceutica Sinica B 2023年第1期13卷 284-297页

作者： Yizhen Wang Qijun Lv You Chen Langtao Xu Miao Feng Zhiyong Xiong Jiajun Li Jie Ren Jie Liu Bo Liu Department of General Surgery the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China School of Biomedical Engineering Sun Yat-sen UniversityGuangzhou 510006China Department of Ultrasound the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Biofilms are closely associated with the tough healing and dysfunctional inflammation of chronic wounds.photothermal therapy(PTT)emerged as a suitable alternative which could destroy the structure of biofilms with local physical heat.However,the efficacy of PTT is limited because the excessive hyperthermia could damage surrounding tissues.Besides,the difficult reserve and delivery of photothermal agents makes PTT hard to eradicate biofilms as expectation.Herein,we present a GelMA-EGF/Gelatin-MPDA-LZM bilayer hydrogel dressing to perform lysozyme-enhanced PTT for biofilms eradication and a further acceleration to the repair of chronic wounds.Gelatin was used as inner layer hydrogel to reserve lysozyme(LZM)loaded mesoporous polydopamine(MPDA)(MPDA-LZM)nanoparticles,which could rapidly liquefy while temperature rising so as to achieve a bulk release of nanoparticles.MPDA-LZM nanoparticles serve as photothermal agents with antibacterial capability,could deeply penetrate and destroy biofilms.In addition,the outer layer hydrogel consisted of gelatin methacryloyl(GelMA)and epidermal growth factor(EGF)promoted wound healing and tissue regeneration.It displayed remarkable efficacy on alleviating infection and accelerating wound healing in vivo.Overall,the innovative therapeutic strategy we came up with has significant effect on biofilms eradication and shows promising application in promoting the repair of clinical chronic wounds.

关键词： Biofilm eradication Chronic wound healing Bilayer hydrogel Nanoparticles Lysozyme photothermal therapy Antibacterial effect Thermo-reversible gel-sol transition

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Silica-based nanoarchitecture for an optimal combination of photothermal and chemodynamic therapy functions of Cu2–xS cores with red emitting carbon dots

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Frontiers of Chemical Science and Engineering 2023年第12期17卷 2144-2155页

作者： Alexey Stepanov Svetlana Fedorenko Kirill Kholin Irek Nizameev Alexey Dovzhenko Rustem Zairov Tatiana Gerasimova Alexandra Voloshina Anna Lyubina Guzel Sibgatullina Dmitry Samigullin Asiya Mustafina Arbuzov Institute of Organic and Physical Chemistry FRC Kazan Scientific Center of RASKazan 420088Russia Department of Physics Kazan National Research Technological UniversityKazan 420015Russia Department of Nanotechnology in Electronics Kazan National Research Technical University named after A.N.Tupolev-KAIKazan 420111Russia Kazan(Volga region)Federal University Kazan 420008Russia Kazan Institute of Biochemistry and Biophysics FRC Kazan Scientific Center of RASKazan 420111Russia

This study introduces multifunctional silica nanoparticles that exhibit both high photothermal and chemodynamic therapeutic activities,in addition to luminescence.The activity of the silica nanoparticles is derived from their plasmonic properties,which are a result of infusing the silica nanoparticles with multiple Cu2-xS cores.This infusion process is facilitated by a recoating of the silica nanoparticles with a cationic surfactant.The key factors that enable the internal incorporation of the Cu2-xS cores and the external deposition of red-emitting carbon dots are identified.The Cu2-xS cores within the silica nanoparticles exhibit both self-boosting generation of reactive oxygen species and high photothermal conversion efficacy,which are essential for photothermal and chemodynamic activities.The silica nanoparticles’small size(no more than 70 nm)and high colloidal stability are prerequisites for their cell internalization.The internalization of the red-emitting silica nanoparticles within cells is visualized using fluorescence microscopy techniques.The chemodynamic activity of the silica nanoparticles is associated with their dark cytotoxicity,and the mechanisms of cell death are evaluated using an apoptotic assay.The photothermal activity of the silica nanoparticles is demonstrated by significant cell death under near-infrared(1064 nm)irradiation.

关键词： copper sulfide nanoparticles chemodynamic therapy photothermal therapy carbon dots silica nanoparticles

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Ultrasound-visualized nanocarriers with siRNA for targeted inhibition of M2-like TAM polarization to enhance photothermal therapy in NSCLC

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Nano Research 2023年第1期16卷 882-893页

作者： Wenhao Lv Chen Xu Hao Wu Yangyang Zhu Ozioma Udochukwu Akakuru Hui Du Fang Nie Aiguo Wu Juan Li Ultrasound Medical Center Lanzhou University Second HospitalGansu Province Clinical Research Center for UltrasonographyGansu Province Medical Engineering Research Center for Intelligence UltrasoundLanzhou 730000China Cixi Institute of Biomedical Engineering International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringCASNingbo 315201China

photothermal therapy(PTT)has received a lot of attention as a promising strategy for eliminating tumors quickly.However,the unavoidable inflammatory response during the treatment might result in a high concentration of M2-like tumor-associated macrophages(TAMs),increasing the risk of tumor recurrence and metastasis.To address this problem,gold-based nanocarriers(PGMP-small interfering RNA(siRNA)nanoparticles(NPs))containing STAT6siRNA,that inhibited M2-like TAM polarization,were designed and investigated for PTT and gene therapy of non-small cell lung cancer(NSCLC).In an NSCLC model,the nanocarriers demonstrated excellent siRNA delivery ability and a high gene transfection rate of up to 90%in macrophages,thus inhibiting the polarization of about 87%of M2-like TAMs and effectively suppressing the invasion and metastasis of NSCLC.Meanwhile,the unique gold nanosphere structure offered improved PTT and contrast-enhanced ultrasound imaging,thus contributing to the efficient elimination and real-time monitoring of the tumor tissues.These nanocarriers with combined gene and photothermal therapeutic capabilities improved the efficacy of single-modality treatment,and showed the potential to inhibit cancer cell recurrence and metastasis to ultimately cure NSCLC.

关键词： gold-based nanocarrier small interfering RNA(siRNA)delivery photothermal therapy M2-like tumor-associated macrophages(TAMs) contrast-enhanced ultrasound imaging non-small cell lung cancer(NSCLC)

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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

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Recent Advances in Bio-Inspired Versatile Polydopamine Platforms for “Smart” Cancer photothermal therapy

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Chinese Journal of Polymer Science 2023年第5期41卷 699-712,I0007页

作者： Zhi-Yuan Ma Dan-Ya Li Xin Jia Rui-Li Wang Mei-Fang Zhu State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and EngineeringDonghua UniversityShanghai 201620China Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan School of Chemistry and Chemical EngineeringShihezi UniversityShihezi 832003China

Although photothermal therapy(PTT)has been developed for fighting cancers,the degradative,toxic,and metabolic nature of photothermal conversion materials(PCMs)has prevented them from being clinically implemented.Taking advantage of the surface modification strategy of mussel-inspired dopamine chemistry and its excellent photothermal conversion effect,polydopamine(Pdop)represents a versatile PTT platform,providing strategies and methods for the construction of novel Pdop-functionalized PCMs.Thanks to its adhesion and secondary reactivity,Pdop can be deposited on virtually all substrates to improve their bioavailability and biocompatibility.Pdop-based PCMs could not be only functionalized with small biomolecules via chemical bonds and/or noncovalent force but also modified with functional polymers via either the“grafting to”or“grafting from”method.This review highlights the synthetic methods,therapeutic strategies,and designs of PCMs based on Pdop in recent years to explore its scope and limitations.

关键词： Polydopamine photothermal therapy Drug delivery systems Polymers Tumor theranostics

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Immunostimulant nanomodulator boosts antitumor immune response in triple negative breast cancer by synergism of vessel normalization and photothermal therapy

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Nano Research 2023年第8期16卷 11149-11163页

作者： Hao Jiang Yilang He Jia Zhao Ruimin Chang Hailun He Tan Li Xingyu Zhang Bo Shu Wenxuan Zhang Huaiyu Wang Jing Liu Shubing Zhang Yuetao Zhao Department of Biomedical Informatics School of Life SciencesCentral South UniversityChangsha 410013China Department of Biochemistry and Molecular Biology Hunan Province Key Laboratory of Basic and Applied HematologySchool of Life SciencesCentral South UniversityChangsha 410013China Department of Cell Biology School of Life SciencesCentral South UniversityChangsha 410013China The Department of Dermatology Xiangya Clinical Research Center for Cancer ImmunotherapyHunan Key Laboratory of Skin Cancer and PsoriasisHunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South UniversityNo.87 Xiangya RoadChangsha 410008China Department of General Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011China State Key Laboratory of Natural and Biomimetic Drugs Department of Chemical BiologySchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Tumor vascular dysfunction and immune suppression predict poor outcomes of tumor therapy.Combination of photothermal therapy(PTT)and vessel normalization with tumor immunotherapy is promising to augment antitumor benefit.Herein,we develop a potential immunostimulatory nanomodulator for treatment of triple-negative breast cancer(TNBC)treatment via synergism of PTT,vessel normalization,and priming of tumoral suppressive immune microenvironment by blocking transforming growth factor-β(TGF-β)pathway.The nanomodulator,namely Vac@Apt@BPs,is developed by conjugation of TGF-βinhibitor Vactosertib(Vac)and nucleolin-recognizing aptamer(Apt)on the surface of black phosphorus nanoparticles(BPs).Vac@Apt@BPs show good accumulation in TNBC via aptamer-induced active targeting of TNBC.Via the blockade of TGF-βsignaling,Vac@Apt@BPs effectively inhibit the formation of tumor neovascular,and normalize the vessels to recover vascular integrity and alleviate the hypoxia stress.Together with the tumor eradication and immunogenic cell death via PTT,robust immune response was boosted by promoted maturation of dendritic cells,suppression of regulatory T cells,and stimulation of effective T cells.This synergistic therapeutic strategy potentially suppresses the growth of TNBC in mice.

关键词： vessel normalization photothermal therapy black phosphorus triple negative breast cancer transforming growth factor-β

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Fish scale-derived scaffolds with MSCs loading for photothermal therapy of bone defect

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Nano Research 2023年第5期16卷 7383-7392页

作者： Siyu Shen Rui Liu Chuanhui Song Tao Shen Yiwen Zhou Junxia Guo Bin Kong 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 SchoolNanjing 210008China Branch of National Clinical Research Center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008China Department of Orthodontics Nanjing Stomatological HospitalMedical School of Nanjing UniversityNanjing 210008China Department of Sports Medicine and Adult Reconstructive Surgery Nanjing Drum Tower HospitalClinical College of Nanjing Medical UniversityNanjing 210008China Department of Biomedical Engineering School of MedicineShenzhen UniversityShenzhen 518060China

Tissue engineering scaffolds have presented effective value in bone repair.However,the integration of the diverse components,complex structures,multifunction to impart the scaffolds with improved applicability is still a challenge.Here,we propose a novel fish-derived scaffold combined with photothermal therapy and mesenchymal stem cells(MSCs)to promote bone regeneration.The fish-derived scaffold is composed of the decellularized fish scale and gelatin methacrylate synthesized from fish gelatin(fGelMA),which can promote the proliferation and osteogenesis of MSCs with no obvious immunological rejection.Furthermore,the black phosphorus(BP)nanosheets are incorporated into the fGelMA hydrogel network,which can endow the hydrogel with the capacity of photothermal conversion stimulated by near-infrared(NIR)light.The fish-derived scaffold can promote the osteogenesis process of MSCs with higher expression of osteogenic markers and higher mineralization assisted by the NIR light in vitro.The regeneration of mice calvarial defect has also been accelerated by the scaffold with photothermal therapy and MSCs.These results suggest that the fish-derived scaffold,photothermal therapy,MSCs-based regenerative therapy is a promising clinical strategy in bone regeneration.

关键词： fish scale GelMA photothermal therapy mesenchymal stem cell bone regeneration

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