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Cell Biomaterials 2025年

作者： Anthony O. Omole Hannah S. Newton Edward Cedrone Kimia Nematpour Shaojun Xie Yongmei Zhao Bao Tran Marina A. Dobrovolskaia Nicole F. Steinmetz Aiiso Yufeng Li Family Department of Chemical and Nano Engineering University of California San Diego La Jolla San Diego CA 92093 USA Shu and K.C. Chien and Peter Farrell Collaboratory University of California San Diego La Jolla San Diego CA 92093 USA Center for Nano-ImmunoEngineering University of California San Diego La Jolla San Diego CA 92093 USA Moores Cancer Center University of California San Diego La Jolla San Diego CA 92093 USA Nanotechnology Characterization Lab Cancer Research Technology Program Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick MD 21702 USA Sequencing Facility Bioinformatics Group Biomedical Informatics and Data Science Directorate Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick MD 21702 USA CCR Sequencing Facility Cancer Research Technology Program Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick MD 21702 USA Department of Bioengineering University of California San Diego La Jolla San Diego CA 92093 USA Department of Radiology University of California San Diego La Jolla San Diego CA USA Institute for Materials Discovery and Design University of California San Diego La Jolla San Diego CA 92093 USA Center for Engineering in Cancer Institute of Engineering Medicine University of California San Diego La Jolla San Diego CA 92093 USA

Cowpea mosaic virus (CPMV) is a plant virus with potent anti-tumor efficacy. Intratumoral CPMV, but not cowpea chlorotic mottle virus (CCMV), reprograms the tumor microenvironment priming durable, systemic anti-tumor immunity. Here, we performed a side-by-side mechanism of action comparison between CPMV and CCMV. Through immune-multiplexing and trafficking studies we observed that CPMV and CCMV are taken up by innate immune cells at similar rates but are processed differently. While CCMV induces proinflammatory interleukins 22, 23, and 27, CPMV is a strong inducer of type I, II, and III interferons, which contribute to the activation and enhancement of immune cell function. We observed that CPMV RNAs activate Toll-like receptor (TLR) 7 upon delivery—and not CCMV RNAs; CPMV RNAs persist longer within cells compared with CCMV. Taken together, this work identifies determinants for CPMV’s unique mechanism for intratumoral immunotherapy. It also broadens our understanding of the utility of plant viruses for biomedical applications.

关键词： plant viruses intratumoral immunotherapy cowpea mosaic virus cowpea chlorotic mottle virus cancer nanotechnology

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Precision targeting of β-catenin induces tumor reprogramming and immunity in hepatocellular cancers

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Nature communications 2025年第1期16卷 5009页

作者： Brandon M Lehrich Evan R Delgado Tyler M Yasaka Silvia Liu Catherine Cao Yuqing Liu Mohammad N Taheri Xiangnan Guan Hartmut Koeppen Sucha Singh Vik Meadows Jia-Jun Liu Anya Singh-Varma Yekaterina Krutsenko Minakshi Poddar T Kevin Hitchens Lesley M Foley Binyong Liang Alex Rialdi Ravi P Rai Panari Patel Madeline Riley Aaron Bell Reben Raeman Tulin Dadali Jason J Luke Ernesto Guccione Mo R Ebrahimkhani Amaia Lujambio Xin Chen Martin Maier Yulei Wang Wendy Broom Junyan Tao Satdarshan P Monga Organ Pathobiology and Therapeutics Institute University of Pittsburgh School of Medicine Pittsburgh PA USA. Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh PA USA. Pittsburgh Liver Research Center University of Pittsburgh and University of Pittsburgh Medical Center Pittsburgh PA USA. Medical Scientist Training Program University of Pittsburgh Pittsburgh PA USA. Department of Pathology Division of Experimental Pathology University of Pittsburgh School of Medicine Pittsburgh PA USA. Department of Bioengineering Swanson School of Engineering University of Pittsburgh Pittsburgh PA USA. Translational Medicine Genentech Inc. San Francisco CA USA. University of Pittsburgh School of Medicine Pittsburgh PA USA. Hepatic Surgery Center Department of Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China. Department of Oncological Sciences Icahn School of Medicine at Mount Sinai New York NY USA. Alnylam Pharmaceuticals Boston MA USA. UPMC Hillman Cancer Center and University of Pittsburgh Pittsburgh PA USA. Cancer Biology Program University of Hawaii Cancer Center Honolulu HI USA. Organ Pathobiology and Therapeutics Institute University of Pittsburgh School of Medicine Pittsburgh PA USA. junyantao2010@***. Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh PA USA. junyantao2010@***. Pittsburgh Liver Research Center University of Pittsburgh and University of Pittsburgh Medical Center Pittsburgh PA USA. junyantao2010@***. Organ Pathobiology and Therapeutics Institute University of Pittsburgh School of Medicine Pittsburgh PA USA. smonga@pitt.edu. Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh PA USA. smonga@pitt.edu. Pittsburgh Liver Research Center University of Pittsburgh and University of Pittsburgh Medical Center Pittsburgh PA USA. smonga

First-line immune checkpoint inhibitor (ICI) combinations show responses in subsets of hepatocellular carcinoma (HCC) patients. Nearly half of HCCs are Wnt-active with mutations in CTNNB1 (encoding for β-catenin), AXIN1/2, or APC, and demonstrate heterogeneous and limited benefit to ICI due to an immune excluded tumor microenvironment. We show significant tumor responses in multiple β-catenin-mutated immunocompetent HCC models to a novel siRNA encapsulated in lipid nanoparticle targeting CTNNB1 (LNP-CTNNB1). Both single-cell and spatial transcriptomics reveal cellular and zonal reprogramming, along with activation of immune regulatory transcription factors IRF2 and POU2F1, re-engaged type I/II interferon signaling, and alterations in both innate and adaptive immunity upon β-catenin suppression with LNP-CTNNB1 at early- and advanced-stage disease. Moreover, ICI enhances response to LNP-CTNNB1 in advanced-stage disease by preventing T cell exhaustion and through formation of lymphoid aggregates (LA). In fact, expression of an LA-like gene signature prognosticates survival for patients receiving atezolizumab plus bevacizumab in the IMbrave150 phase III trial and inversely correlates with CTNNB1-mutatational status in this patient cohort. In conclusion, LNP-CTNNB1 is efficacious as monotherapy and in combination with ICI in CTNNB1-mutated HCCs through impacting tumor cell-intrinsic signaling and remodeling global immune surveillance, providing rationale for clinical investigations.

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Sucrose-based cryoprotective storage of extracellular vesicles

Extracellular vesicle

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Extracellular vesicle 2022年 1卷 100016页

作者： Sierra A Walker Irina Davidovich Yubo Yang Andrew Lai Jenifer Pendiuk Goncalves Vatsal Deliwala Sara Busatto Shane Shapiro Na'ama Koifman Carlos Salomon Yeshayahu Talmon Joy Wolfram Department of Biochemistry and Molecular Biology Department of Physiology and Biomedical Engineering Department of Transplantation Mayo Clinic Jacksonville FL 32224 USA. Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute (RBNI) Technion-Israel Institute of Technology Haifa 3200003 Israel. Exosome Biology Laboratory Centre for Clinical Diagnostics University of Queensland Centre for Clinical Research Royal Brisbane and Women's Hospital Faculty of Medicine The University of Queensland Brisbane QLD 4006 Australia. Australian Institute for Bioengineering and Nanotechnology The University of Queensland Brisbane QLD 4072 Australia. School of Chemical Engineering The University of Queensland Brisbane QLD Australia. Vascular Biology Program Boston Children's Hospital Boston MA 02115 United States. Department of Surgery Harvard Medical School Boston MA 02115 United States. Department of Orthopedic Surgery Mayo Clinic Jacksonville FL 32224 USA. Center of Microscopy and Microanalysis The University of Queensland Brisbane QLD 4072 Australia. Departamento de Investigación Postgrado y Educación Continua (DIPEC) Facultad de Ciencias de la Salud Universidad del Alba Santiago 8320000 Chile.

Advancements in extracellular vesicle (EV) studies necessitate the development of optimized storage conditions to ensure preservation of physical and biochemical characteristics. In this study, the most common buffer for EV storage (phosphate-buffered saline/PBS) was compared to a cryoprotective 5% sucrose solution. The size distribution and concentration of EVs from two different sources changed to a greater extent after -80 °C storage in PBS compared to the sucrose solution. Additionally, molecular surface protrusions and transmembrane proteins were more prevalent in EVs stored in the sucrose solution compared to those stored in PBS. This study demonstrates, for the first time, that distinct ring-like molecular complexes and cristae-like folded membranous structures are visible upon EV degradation. Taken together, the size, concentration, molecular surface extensions, and transmembrane proteins of EVs varied substantially based on the buffer used for -80 °C storage, suggesting that biocompatible cryoprotectants, such as sucrose, should be considered for EV studies.

关键词： Cryoprotection exosome extracellular vesicle storage sucrose

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Modulation of Foreign Body Reaction against PDMS Implant by Grafting Topographically Different Poly(Acrylic Acid) Micropatterns

SSRN

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SSRN 2019年

作者： Lee, Jae Sang Shin, Byung Ho Yoo, Byoung Yong Nam, Sun-Young Lee, Miji Park, Hansoo Choy, Young Bin Heo, Chan Yeong Koh, Won-Gun Department of Chemical and Biomolecular Engineering Yonsei University Seoul03722 Korea Republic of Department of Biomedical Engineering College of Medicine Seoul National University Seoul03080 Korea Republic of Interdisciplinary Program for Bioengineering College of Engineering Seoul National University Seoul08826 Korea Republic of Institute of Medical & Biological Engineering Medical Research Center Seoul National University Seoul03080 Korea Republic of Department of Plastic and Reconstructive Surgery College of Medicine Seoul National University Seoul03080 Korea Republic of Department of Plastic and Reconstructive Surgery Seoul National University Bundang Hospital Seongnam13620 Korea Republic of School of Integrative Engineering Chung-Ang University Korea Republic of

The surface of poly(dimethylsiloxane) (PDMS) was grafted with poly(acrylic acid) (PAA) layers via surface-initiated photopolymerization to suppress the capsular contracture resulting from a foreign body reaction. Owing to the nature of photo-induced polymerization, various PAA micropatterns could be fabricated using photolithography. Hole and stripe micropatterns approximately 100-μm wide and 3-μm thick were grafted onto the PDMS surface without delamination. The incorporation of PAA micropatterns provided not only chemical cues by hydrophilic PAA microdomains but also topographical cues by hole or stripe micropatterns. In vitro studies revealed that a PAA-grafted PDMS surface had a lower proliferation of both macrophages and fibroblasts regardless of the pattern presence. However, PDMS with PAA micropatterns, especially stripe micropatterns, minimized the aggregation of fibroblasts and their subsequent differentiation into myofibroblasts. An in vivo study also showed that PDMS samples with stripe micropatterns polarized macrophages into anti-inflammatory M2 macrophages and most effectively inhibited capsular contracture, which was demonstrated by investigating the inflammation score, transforming-growth-factor-β expression, number of macrophages, and myofibroblasts as well as the collagen density and capsule thickness. © 2019, The Authors. All rights reserved.

关键词： Macrophages

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Neuroprosthetics: Durable and Fatigue-Resistant Soft Peripheral Neuroprosthetics for In Vivo Bidirectional Signaling (Adv. Mater. 20/2021)

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Advanced Materials 2021年第20期33卷

作者： Hyunseon Seo Sang Ihn Han Kang-Il Song Duhwan Seong Kyungwoo Lee Sun Hong Kim Taesung Park Ja Hoon Koo Mikyung Shin Hyoung Won Baac Ok Kyu Park Soong Ju Oh Hyung-Seop Han Hojeong Jeon Yu-Chan Kim Dae-Hyeong Kim Taeghwan Hyeon Donghee Son School of Medicine Sungkyunkwan University Suwon 16419 Republic of Korea Center for Biomaterials Biomedical Research Institute Korea Institute of Science and Technology Seoul 02792 Republic of Korea Center for Nanoparticle Research Institute of Basic Science (IBS) Seoul 08826 Republic of Korea School of Chemical and Biological Engineering Seoul National University Seoul 08826 Republic of Korea Medical Device Development Center Daegu-Gyeongbuk Medical Innovation Foundation Daegu 41061 Republic of Korea Department of Electrical and Computer Engineering Sungkyunkwan University Suwon 16419 Republic of Korea Department of Electrical and Computer Engineering Inter-University Semiconductor Research Center Seoul National University Seoul 08826 Republic of Korea Department of Materials Science and Engineering Korea University Seoul 02841 Republic of Korea Interdisciplinary Program for Bioengineering Seoul National University Seoul 08826 Republic of Korea Department of Biomedical Engineering SKKU Institute for Convergence Sungkyunkwan University Suwon 16419 Republic of Korea Center for Neuroscience Imaging Research Institute for Basic Science (IBS) Suwon 16419 Republic of Korea Department of Superintelligence Engineering Sungkyunkwan University Suwon 16419 Republic of Korea

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Extended experimental inferential structure determination method for evaluating the structural ensembles of disordered protein states

arXiv

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arXiv 2019年

作者： Lincoff, James Krzeminski, Mickael Haghighatlari, Mojtaba Teixeira, João M.C. Gomes, Gregory-Neal W. Gradinaru, Claudiu C. Forman-Kay, Julie D. Head-Gordon, Teresa Department of Chemical and Biomolecular Engineering University of California BerkeleyCA94720 United States Pitzer Center for Theoretical Chemistry University of California BerkeleyCA94720 Molecular Structure and Function Program Hospital for Sick Children TorontoONM5G 0A4 Canada Department of Biochemistry University of Toronto TorontoONM5S 1A8 Canada Department of Chemical and Physical Sciences University of Toronto Mississauga MississaugaONL5L 1C6 Canada Department of Chemistry University of California BerkeleyCA94720 United States Department of Bioengineering University of California BerkeleyCA94720 United States

Characterization of proteins with intrinsic or unfolded state disorder comprises a new frontier in structural biology, requiring the characterization of diverse and dynamic structural ensembles. We introduce a comprehensive Bayesian framework, the Extended Experimental Inferential Structure Determination (X-EISD) method, that calculates the maximum log-likelihood of a protein structural ensemble by accounting for the uncertainties of a wide range of experimental data and back-calculation models from structures, including NMR chemical shifts, J-couplings, Nuclear Overhauser Effects, paramagnetic relaxation enhancements, residual dipolar couplings, and hydrodynamic radii, single molecule fluorescence Förster resonance energy transfer efficiencies and small angle X-ray scattering intensity curves. We apply X-EISD to the drkN SH3 unfolded state domain and show that certain experimental data types are more influential than others for both eliminating structural ensemble models, while also finding equally probable disordered ensembles that have alternative structural properties that will stimulate further experiments to discriminate between them. Copyright © 2019, The Authors. All rights reserved.

关键词： Proteins

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Large-scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop

Journal of Extracellular Biology

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Journal of Extracellular Biology 2022年第10期1卷 e63页

作者： Paolini, Lucia Monguió-Tortajada, Marta Costa, Marta Antenucci, Fabio Barilani, Mario Clos-Sansalvador, Marta Andrade, André Cronemberger Driedonks, Tom A. P. Giancaterino, Sara Kronstadt, Stephanie M. Mizenko, Rachel R. Nawaz, Muhammad Osteikoetxea, Xabier Pereira, Carla Shrivastava, Surya Boysen, Anders Toftegaard van de Wakker, Simonides Immanuel van Herwijnen, Martijn J. C. Wang, Xiaoqin Watson, Dionysios C. Gimona, Mario Kaparakis-Liaskos, Maria Konstantinov, Konstantin Lim, Sai Kiang Meisner-Kober, Nicole Stork, Michiel Nejsum, Peter Radeghieri, Annalisa Rohde, Eva Touzet, Nicolas Wauben, Marca H. M. Witwer, Kenneth W. Bongiovanni, Antonella Bergese, Paolo Department of Molecular and Translational Medicine University of Brescia Brescia Italy Center for Colloid and Surface Science (CSGI) Department of Chemistry University of Florence Sesto Fiorentino (FI) Italy Department of Medical and Surgical Specialties Radiological Sciences and Public Health University of Brescia Brescia Italy CREC Research Program Health Science Research Institute Germans Trias i Pujol (IGTP) Badalona Spain Heart Institute (iCor) Cardiology Department Germans Trias i Pujol University Hospital Badalona Spain iBET Instituto de Biologia Experimental e Tecnológica Oeiras Portugal Instituto de Tecnologia Química e Biológica António Xavier Universidade Nova de Lisboa Oeiras Portugal Department of Veterinary and Animal Sciences University of Copenhagen Copenhagen Denmark Laboratory of Regenerative Medicine ‒ Cell Factory Department of Transfusion Medicine and Hematology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy REMAR-IGTP Group Germans Trias i Pujol Research Institute (IGTP) & Nephrology Department University Hospital Germans Trias i Pujol (HUGTiP) Catalonia Badalona (Barcelona) Spain Department of Cell Biology Physiology and Immunology Universitat Autònoma de Barcelona (UAB) Bellaterra Spain Experimental and Clinical Cell Therapy Institute (ExCT) Spinal Cord Injury and Tissue Regeneration Center Paracelsus Medical University Salzburg Austria CDL Research University Medical Center Utrecht Utrecht University Utrecht Netherlands Department of Molecular and Comparative Pathology Johns Hopkins School of Medicine Baltimore MD United States Department of Civil Chemical Environmental and Materials Engineering Alma Mater Studiorum University of Bologna Bologna Italy Fischell Department of Bioengineering University of Maryland College Park MD United States Department of Biomedical Engineering University of California Davis CA United States Department of Rheumatology and Inflammation Research Institute of Medicine

Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, “The Extracellular Vesicle Foundry” (evFOUNDRY) and “Extracellular vesicles from a natural source for tailor-made nanomaterials” (VES4US), organized a workshop entitled “massivEVs” to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during “massivEVs”, the most important points raised, and the points of consensus reached after discussion among academia and industry representatives. Overall, the review of the existing EV manufacturing, upscaling challenges and directions for their resolution highlighted in the workshop painted an optimistic future for the expanding EV field. © 2022 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

关键词： EV-based products extracellular vesicles ISEV workshop large-scale production manufacturing processing regulatory issues

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Cytocompatible magnetostrictive microstructures for nano- A nd microparticle manipulation on linear strain response piezoelectrics

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Multifunctional Materials 2018年第1期1卷

作者： Xiao, Zhuyun Khojah, Reem Chooljian, Marc Conte, Roberto Lo Schneider, Joseph D. Fitzell, Kevin Chopdekar, Rajesh V. Wang, Yilian Scholl, Andreas Chang, Jane Carman, Gregory P. Bokor, Jeffrey Carlo, Dino Di Candler, Rob N. Department of Electrical and Computer Engineering University of California Los Angeles United States Department of Bioengineering University of California Los Angeles United States University of California Berkeley UCSF Graduate Program in Bioengineering Berkeley United States Department of Electrical Engineering and Computer Sciences University of California Berkeley United States Department of Mechanical and Aerospace Engineering University of California Los Angeles United States Department of Chemical and Biomolecular Engineering University of California Los Angeles United States Advanced Light Source Lawrence Berkeley National Laboratory Berkeley United States California Nanosystems Institute Los Angeles United States

In this work, we investigate polycrystalline Ni and FeGamagnetostrictivemicrostructures on prepoled (011)-cut single crystal [Pb(Mg1/3Nb2/3)O3]1-x-[PbTiO3]x (PMN-PT, x ≈ 0.31) with linear strain profile versus applied electric field. Magnetostrictive microstructure arrays with various geometries are patterned on PMN-PT. Functionalizedmagnetic beads are trapped by localized stray fields originating fromthe microstructures. With an applied electric field, themagnetic domains are actuated, inducing the motion of the coupled particles with sub-micrometer precision. This work shows promise of using energy-efficient electric-field-controlled magnetostrictivemicro- A nd nanostructures formanipulatingmagnetic beads via a linear strain response. The work also demonstrates the viability of cells suspended in solution on these structures when subject to applied electric fields, proving the cytocompatibility of the platform for live cell sorting applications. © 2018 IOP Publishing Ltd.

关键词： Electric fields

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Cover Feature: Characterization of a Tryptophan 6-Halogenase fromStreptomyces albusand Its Regioselectivity Determinants (ChemBioChem 10/2020)

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ChemBioChem 2020年第10期21卷 1386-1386页

作者： Jeongchan Lee Dr. Joonwon Kim Hyun Kim Eun-Jung Kim Prof. Dr. Hee-Jin Jeong Prof. Dr. Kwon-Young Choi Prof. Dr. Byung-Gee Kim School of Chemical and Biological Engineering Seoul National University Gwanak-ro 1 Gwanak-gu Seoul 08826 Republic of Korea Institute of Molecular Biology and Genetics Seoul National University Gwanak-ro 1 Gwanak-gu Seoul 08826 Republic of Korea Institute of Engineering Research Seoul National University Gwanak-ro 1 Gwanak-gu Seoul 08826 Republic of Korea Department of Biological and Chemical Engineering Hongik University Sejong-ro 2639 Jochiwon-eup Sejong 30016 Republic of Korea Department of Environmental Engineering Ajou University World cup-ro 206 Yeongtong-gu Suwon 16499 Republic of Korea Institute of Bioengineering in Bio-Max Seoul National University Gwanak-ro 1 Gwanak-gu Seoul 08826 Republic of Korea Interdisciplinary Program of Bioengineering Seoul National University Gwanak-ro 1 Gwanak-gu Seoul 08826 Republic of Korea

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Multifunctional stimuli responsive polymer-gated iron and gold-embedded silica nano golf balls:Nanoshuttles for targeted on-demand theranostics

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Bone Research 2017年第4期5卷 343-356页

作者： Liping Wang Grace Jang Deependra Kumar Ban Vrinda Sant Jay Seth Sami Kazmi Nirav Patel Qingqing Yang Joon Lee Woraphong Janetanakit Shanshan Wang Brian P Head Gennadi Glinsky Ratneshwar Lai School of Biomedical Engineering Shanghai Jiaotong UniverityShanghaiChina Department of Mechanical and Aerospace Engineering La JollaCAUSA Materials Science and Engineering Program La JollaCAUSA Department of Nanoengineering La JollaCAUSA Department of Chemical Engineering University of California San DiegoLa JollaCAUSA Departrnenf of Bioengineering La JollaCAUSA Department of Anesthesiology La JollaCAUSA Veterans Affairs San Diego Healthcare System San DiegoCAUSA Institute of Engineering in Medicine La JollaCAUSA

Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles （NP）-embedded silica nanoshuttles （MGNSs） with nanopores on their surface. Fluorescently labeled Doxombicin （DOX）, a cancer drug, was loaded in the MGNSs as a payload. DOX loaded MGNSs were encapsulated in heat and pH sensitive polymer P（NIPAM-co- MAA） to enable controlled release of the payload. Magnetically-guided transport of MGNSs was examined in：（a） a glass capillary tube to simulate their delivery via blood vessels; and （b） porous hydrogels to simulate their transport in composite human tissues, including bone, cartilage, tendon, muscles and blood-brain barrier {BBB）. The viscoelastic properties of hydrogels were examined by atomic force microscopy （AFM）. Cellular uptake of DOX- loaded MGNSs and the subsequent pH and temperature-mediated release were demonstrated in differentiated human neurons derived from induced pluripotent stem cells （iPSCs） as well as epithelial HeLa cells. The presence of embedded iron and gold NPs in silica shells and polymer-coating are supported by SEM and TEM. Fluorescence spectroscopy and microscopy documented DOX loading in the MGNSs. Time-dependent transport of MGNSs guided by an external magnetic field was observed in both glass capillary tubes and in the porous hydrogel. AFM results affirmed that the stiffness of the hydrogels model the rigidity range from soft tissues to bone. pH and temperature-dependent drug release analysis showed stimuli responsive and gradual drug release. Cells＇ viability MTT assays showed that MGNSs are non-toxic. The cell death from on-demand DOX release was observed in both neurons and ep

关键词： Multifunctional stimuli responsive polymer-gated iron

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