[논문]Biomimetic lipid Nanocomplexes incorporating STAT3-inhibiting peptides effectively infiltrate the lung barrier and ameliorate pulmonary fibrosis

Keum, Hyeongseop; Kim, Jinjoo; Yoo, Dohyun; Kim, Tae Woo; Seo, Changjin; Kim, Dohyeon; Jon, Sangyong

doi:10.1016/j.jconrel.2021.02.022

[해외논문] Biomimetic lipid Nanocomplexes incorporating STAT3-inhibiting peptides effectively infiltrate the lung barrier and ameliorate pulmonary fibrosis

Journal of controlled release : official journal of the Controlled Release Society, v.332, 2021년, pp.160 - 170

Keum, Hyeongseop (KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro) , Kim, Jinjoo (KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro) , Yoo, Dohyun (KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro) , Kim, Tae Woo (KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro) , Seo, Changjin (KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro) , Kim, Dohyeon (KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Adv) , Jon, Sangyong

Abstract ▼ AI-Helper

Abstract Activation of signal transducer and activator of transcription 3 (STAT3) under conditions of inflammation plays a crucial role in the pathogenesis of life-threatening pulmonary fibrosis (PF), initiating pro-fibrotic signaling following its phosphorylation. While there have been attempts to interfere with STAT3 activation and associated signaling as a strategy for ameliorating PF, potent inhibitors with minimal systemic toxicity have yet to be developed. Here, we assessed the in vitro and in vivo therapeutic effectiveness of a cell-permeable peptide inhibitor of STAT3 phosphorylation, designated APTstat3-9R, for ameliorating the indications of pulmonary fibrosis. Our results demonstrate that APTstat3-9R formulated with biomimetic disc-shaped lipid nanoparticles (DLNPs) markedly enhanced the penetration of pulmonary surfactant barrier and alleviated clinical symptoms of PF while causing negligible systemic cytotoxicity. Taken together, our findings suggest that biomimetic lipid nanoparticle-assisted pulmonary delivery of APTstat3-9R may be a feasible therapeutic option for PF in the clinic, and could be applied to treat other fibrotic diseases. Highlights STAT3 plays a crucial role in the pathogenesis of pulmonary fibrosis. A cell-permeable peptide inhibitor of STAT3 (APTstat3-9R) hinders the phosphorylation of STAT3. APTstat3-9R formulated with biomimetic phospholipids markedly enhanced the lung barrier penetration. Intratracheal delivery of APTstat3-9R@DLNPs alleviated clinical symptoms of pulmonary fibrosis. Graphical abstract [DISPLAY OMISSION]

Keyword

참고문헌 (74)

New Engl. J. Med. Lederer 378 19 1811 2018 10.1056/NEJMra1705751 Idiopathic pulmonary fibrosis

상세보기
Am. J. Med. Lee 123 4 304 2010 10.1016/j.amjmed.2009.07.033 Does chronic microaspiration cause idiopathic pulmonary fibrosis?

상세보기
Am. J. Epidemiol. Baumgartner 152 4 307 2000 10.1093/aje/152.4.307 Occupational and environmental risk factors for idiopathic pulmonary fibrosis: a multicenter case-control study

상세보기
Mucosal Immunol. Wilson 2 2 103 2009 10.1038/mi.2008.85 Pulmonary fibrosis: pathogenesis, etiology and regulation

상세보기
Sci. Transl. Med. Ng 11 511 2019 10.1126/scitranslmed.aaw1237 Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis

상세보기
Nat. Rev. Drug Discov. Mora 16 11 2017 Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease (vol 16, pg 755, 2017)
Am. J. Resp. Crit. Care Gutierrez 197 2018 Weight loss in patients on antifibrotic therapy for IPF (Idiopathic Pulmonary Fibrosis): a single center retrospective review
Sci. Transl. Med. Marudamuthu 11 522 2019 10.1126/scitranslmed.aat2848 Caveolin-1-derived peptide limits development of pulmonary fibrosis

상세보기
Sci. Rep. UK Ikeda 7 2017 Low body surface area predicts hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis
Lancet Respir. Med. Spagnolo 8 8 750 2020 10.1016/S2213-2600(20)30222-8 Pulmonary fibrosis secondary to COVID-19: a call to arms?

상세보기
Lancet Respir. Med. George 8 8 807 2020 10.1016/S2213-2600(20)30225-3 Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy

상세보기
Eur. J. Prev. Cardiol. Gentile 27 13 1442 2020 10.1177/2047487320932695 COVID-19 and risk of pulmonary fibrosis: the importance of planning ahead

상세보기
Eur. Respir. J. Ballester 46 2015 Role of JAK2/STAT3 pathway in vascular function of pulmonary fibrosis patients
J. Immunol. Le 193 7 3755 2014 10.4049/jimmunol.1302470 Blockade of IL-6 trans signaling attenuates pulmonary fibrosis

상세보기
FASEB J. Pedroza 30 1 129 2016 10.1096/fj.15-273953 STAT-3 contributes to pulmonary fibrosis through epithelial injury and fibroblast-myofibroblast differentiation

상세보기
Sci. Transl. Med. Celada 10 460 2018 10.1126/scitranslmed.aar8356 PD-1 up-regulation on CD4(+) T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-beta 1 production

상세보기
Cell Death Dis. Meng 7 2016 10.1038/cddis.2016.402 Inflammatory macrophages can transdifferentiate into myofibroblasts during renal fibrosis

상세보기
Front. Immunol. Braga 6 2015 10.3389/fimmu.2015.00602 Macrophages during the Fibrotic Process: M2 as Friend and Foe

상세보기
Sci. Signal. Lodyga 12 564 2019 10.1126/scisignal.aao3469 Cadherin-11-mediated adhesion of macrophages to myofibroblasts establishes a profibrotic niche of active TGF-beta

상세보기
Sci. Transl. Med. Kim 11 501 2019 10.1126/scitranslmed.aau2814 Calpain 9 as a therapeutic target in TGF beta-induced mesenchymal transition and fibrosis

상세보기
J. Biol. Chem. Tang 292 10 4302 2017 10.1074/jbc.M116.773085 Transforming growth factor-beta (TGF-beta) directly activates the JAK1-STAT3 Axis to induce hepatic fibrosis in coordination with the SMAD pathway

상세보기
Nat. Commun. Chakraborty 8 2017 10.1038/s41467-017-01236-6 Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis

상세보기
Angew. Chem. Int. Ed. Eng. Kim 51 8 1890 2012 10.1002/anie.201107894 Bio-inspired design and potential biomedical applications of a novel class of high-affinity peptides

상세보기
Cancer Res. Kim 74 8 2144 2014 10.1158/0008-5472.CAN-13-2187 A specific STAT3-binding peptide exerts Antiproliferative effects and antitumor activity by inhibiting STAT3 phosphorylation and signaling

상세보기
ACS Nano Kim 12 7 6904 2018 10.1021/acsnano.8b02330 Nanoparticle-assisted transcutaneous delivery of a signal transducer and activator of transcription 3-inhibiting peptide ameliorates psoriasis-like skin inflammation

상세보기
J. Toxicol. Pathol. Hasegawa-Baba 27 3-4 197 2014 10.1293/tox.2014-0022 Intratracheal instillation methods and the distribution of administered material in the lung of the rat

상세보기
Jove-J. Vis. Exp. Cai 81 2013 Noninvasive intratracheal intubation to study the pathology and physiology of Mouse Lung
J. Control. Release Wang 314 12 2019 10.1016/j.jconrel.2019.10.030 Treatment of acute lung injury and early- and late-stage pulmonary fibrosis with combination emulsion siRNA polyplexes

상세보기
Adv. Colloid Interfac. Arick 225 218 2015 10.1016/j.cis.2015.10.002 Effects of nanoparticles on the mechanical functioning of the lung

상세보기
Nat. Biotechnol. Blanco 33 9 941 2015 10.1038/nbt.3330 Principles of nanoparticle design for overcoming biological barriers to drug delivery

상세보기
Int. J. Mol. Sci. Paranjpe 15 4 5852 2014 10.3390/ijms15045852 Nanoparticle-mediated pulmonary drug delivery: a review

상세보기
Phys. Chem. Chem. Phys. Xu 19 27 17568 2017 10.1039/C7CP02548C Transport of nanoparticles across pulmonary surfactant monolayer: a molecular dynamics study

상세보기
Bba-Biomembranes Zhang 1848 1 329 2015 10.1016/j.bbamem.2014.05.008 Characterizing the structure of lipodisq nanoparticles for membrane protein spectroscopic studies

상세보기
J. Control. Release Park 163 2 111 2012 10.1016/j.jconrel.2012.08.029 Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging

상세보기
J. Mater. Chem. B Park 1 36 4576 2013 10.1039/c3tb20613k HER2-specific aptide conjugated magneto-nanoclusters for potential breast cancer imaging and therapy

상세보기
Biomaterials Jo 35 9 3052 2014 10.1016/j.biomaterials.2013.12.031 VEGF-binding aptides and the inhibition of choroidal and retinal neovascularization

상세보기
J. Control. Release Kim 256 114 2017 10.1016/j.jconrel.2017.04.036 An approach for half-life extension and activity preservation of an anti-diabetic peptide drug based on genetic fusion with an albumin-binding aptide

상세보기
Nanotechnology Kim 27 48 2016 10.1088/0957-4484/27/48/48LT01 Self-assembled nanoparticles comprising aptide-SN38 conjugates for use in targeted cancer therapy

상세보기
J. Exp. Med. Wynn 208 7 1339 2011 10.1084/jem.20110551 Integrating mechanisms of pulmonary fibrosis

상세보기
Annu. Rev. Physiol. Chapman 73 413 2011 10.1146/annurev-physiol-012110-142225 Epithelial-Mesenchymal interactions in pulmonary fibrosis

상세보기
Respir. Res. Rout-Pitt 19 2018 10.1186/s12931-018-0834-8 Epithelial mesenchymal transition (EMT): a universal process in lung diseases with implications for cystic fibrosis pathophysiology

상세보기
J. R. Soc. Interface Harishchandra 7 S15 2010 10.1098/rsif.2009.0329.focus Nanoparticle interaction with model lung surfactant monolayers

상세보기
Respir. Physiol. Neurobiol. Halpern 163 1-3 222 2008 10.1016/j.resp.2008.05.012 Liquid and surfactant delivery into pulmonary airways

상세보기
Eur. Respir. J. Pugashetti 52 3 2018 10.1183/13993003.01289-2018 Weight loss as a predictor of mortality in patients with interstitial lung disease

상세보기
Eur. Respir. J. Burgstaller 50 1 2017 10.1183/13993003.01805-2016 The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease

상세보기
Front. Pharmacol. Li 8 2017 10.3389/fphar.2017.00513 Astragaloside IV improves bleomycin-induced pulmonary fibrosis in rats by attenuating extracellular matrix deposition

상세보기
Sci. Rep. UK Rosmark 8 2018 Quantifying extracellular matrix turnover in human lung scaffold cultures
J. Immunol. Feng 191 9 4828 2013 10.4049/jimmunol.1202673 Neuraminidase reprograms lung tissue and potentiates lipopolysaccharide-induced acute lung injury in mice

상세보기
Respir. Res. Matsuyama 9 2008 10.1186/1465-9921-9-79 Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors: an experimental study

상세보기
J. Cardiothor. Vasc. An. Assaad 32 2 901 2018 10.1053/j.jvca.2017.08.028 Assessment of pulmonary edema: principles and practice

상세보기
Mol. Cell. Biol. Sonnenblick 24 24 10584 2004 10.1128/MCB.24.24.10584-10592.2004 Interplay between MITF, PIAS3, and STAT3 in mast cells and melanocytes

상세보기
J. Immunol. Ding 196 11 4477 2016 10.4049/jimmunol.1502043 STAT3 signaling in B cells is critical for germinal center maintenance and contributes to the pathogenesis of murine models of lupus

상세보기
Nat. Commun. Pan 9 2018 10.1038/s41467-018-06134-z STAT3-coordinated migration facilitates the dissemination of diffuse large B-cell lymphomas

상세보기
Hepatology Kim 47 4 1363 2008 10.1002/hep.22109 Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease

상세보기
Steatohep. Steatos. Hepatol. Barnes 57 5 1980 2013 10.1002/hep.26169 Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury

상세보기
Hepatology Nathwani 41 2 380 2005 10.1002/hep.20548 Serum alanine aminotransferase in skeletal muscle diseases

상세보기
Circ-Heart Fail Brisco 6 2 233 2013 10.1161/CIRCHEARTFAILURE.112.968230 Blood urea nitrogen/Creatinine ratio identifies a high-risk but potentially reversible form of renal dysfunction in patients with decompensated heart failure

상세보기
Mayo Clin. Proc. Paige 84 2 180 2009 10.4065/84.2.180 The top 10 things nephrologists wish every primary care physician knew

상세보기
Respir. Res. Zhang 19 2018 10.1186/s12931-018-0864-2 Macrophages: friend or foe in idiopathic pulmonary fibrosis?

상세보기
Cell Commun. Signal Hou 16 2018 10.1186/s12964-018-0300-8 M2 macrophages promote myofibroblast differentiation of LR-MSCs and are associated with pulmonary fibrogenesis

상세보기
Trends Mol. Med. Byrne 22 4 303 2016 10.1016/j.molmed.2016.02.004 Pulmonary macrophages: a new therapeutic pathway in Fibrosing lung disease?

상세보기
Bba-Biomembranes Veldhuizen 1467 2 255 2000 10.1016/S0005-2736(00)00256-X Role of pulmonary surfactant components in surface film formation and dynamics

상세보기
Bba-Mol. Basis Dis. Veldhuizen 1408 2-3 90 1998 10.1016/S0925-4439(98)00061-1 The role of lipids in pulmonary surfactant

상세보기
J. Lipid Res. Yu 42 9 1421 2001 10.1016/S0022-2275(20)30274-1 Dipalmitoylphosphatidylcholine and cholesterol in monolayers spread from adsorbed films of pulmonary surfactant

상세보기
Biomaterials Sun 192 51 2019 10.1016/j.biomaterials.2018.10.045 Native nanodiscs from blood inhibit pulmonary fibrosis

상세보기
Int. J. Exp. Pathol. Izbicki 83 3 111 2002 10.1046/j.1365-2613.2002.00220.x Time course of bleomycin-induced lung fibrosis

상세보기
J. Autoimmun. Francois 56 1 2015 10.1016/j.jaut.2014.08.003 B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis

상세보기
J. Immunol. Xue 191 5 2089 2013 10.4049/jimmunol.1203476 Plasma B lymphocyte stimulator and B cell differentiation in idiopathic pulmonary fibrosis patients

상세보기
PLoS One Donahoe 10 7 2015 10.1371/journal.pone.0133684 Autoantibody-targeted treatments for acute exacerbations of idiopathic pulmonary fibrosis (vol 10, e0127771, 2015)

상세보기
Respirology Keir 19 353 2014 10.1111/resp.12214 Rituximab in severe, treatment refractory connective tissue disease associated interstitial lung disease

상세보기
DNA Cell Biol. Veerappan 32 4 206 2013 10.1089/dna.2013.2005 Mast cells: a pivotal role in pulmonary fibrosis

상세보기
Mayo Clin. Proc. Hempel 67 10 1009 1992 10.1016/S0025-6196(12)60936-7 The mast-cell and idiopathic pulmonary fibrosis

상세보기
Small Barbosa-Barros 8 6 807 2012 10.1002/smll.201101545 Bicelles: lipid nanostructured platforms with potential dermal applications

상세보기
Int. J. Pharm. Rubio 386 1-2 108 2010 10.1016/j.ijpharm.2009.11.004 Bicellar systems for in vitro percutaneous absorption of diclofenac

상세보기

LOADING...

활용도 분석정보

상세보기

다운로드

내보내기

활용도 Top5 논문

해당 논문의 주제분야에서 활용도가 높은 상위 5개 콘텐츠를 보여줍니다.
더보기 버튼을 클릭하시면 더 많은 관련자료를 살펴볼 수 있습니다.

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증