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Article ; Online: Targeted treatment of gouty arthritis by biomineralized metallic nanozyme-mediated oxidative stress-mitigating nanotherapy.

Mohapatra, Adityanarayan / Mohanty, Ayeskanta / Sathiyamoorthy, Padmanaban / Chahal, Sahil / Vijayan, Veena / Rajendrakumar, Santhosh Kalash / Park, In-Kyu

Journal of materials chemistry. B

2023 Volume 11, Issue 32, Page(s) 7684–7695

Abstract: Gouty arthritis is characterized by chronic deposition of monosodium urate (MSU) crystals in the joints and other tissues, resulting in the production of excess reactive oxygen species (ROS) and proinflammatory cytokines that intensify synovial ... ...

Abstract	Gouty arthritis is characterized by chronic deposition of monosodium urate (MSU) crystals in the joints and other tissues, resulting in the production of excess reactive oxygen species (ROS) and proinflammatory cytokines that intensify synovial inflammation. This condition is mainly associated with inflammatory M1 macrophage activation and oxidative stress production. Hence, gout symptoms can often be resolved by eliminating M1 macrophage activation and scavenging oxidative stress in the inflamed areas. Herein, we developed M1-macrophage-targeting biomineralized metallic nanozymes (FALNZs) that deplete oxidative stress and reduce the M1 macrophage levels to mitigate gouty arthritis. Intra-articular injection of the FALNZs targets inflammatory macrophages and suppresses ROS levels in joints with MSU-crystal-induced arthritis. In addition, the FALNZs alleviate joint swelling, inflammatory cytokine production, and pathological features of the joints. Overall, the proposed therapeutic approach is biocompatible and is an effective ROS scavenger for the treatment of gouty pathogenesis.
MeSH term(s)	Humans ; Arthritis, Gouty/chemically induced ; Arthritis, Gouty/drug therapy ; Reactive Oxygen Species ; Uric Acid ; Inflammation/drug therapy ; Inflammation/pathology ; Oxidative Stress
Chemical Substances	Reactive Oxygen Species ; Uric Acid (268B43MJ25)
Language	English
Publishing date	2023-09-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2702241-9
ISSN	2050-7518 ; 2050-750X
ISSN (online)	2050-7518
ISSN	2050-750X
DOI	10.1039/d3tb00669g
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Thermosusceptible Nitric-Oxide-Releasing Nitrogel for Strengthening Antitumor Immune Responses with Tumor Collagen Diminution and Deep Tissue Delivery during NIR Laser-Assisted Photoimmunotherapy.

Mohapatra, Adityanarayan / Mondal, Jagannath / Sathiyamoorthy, Padmanaban / Mohanty, Ayeskanta / Revuri, Vishnu / Rajendrakumar, Santhosh Kalash / Lee, Yong-Kyu / Park, In-Kyu

ACS applied materials & interfaces

2023

Abstract: Combined cancer immunotherapy has demonstrated promising potential with an amplified antitumor response and immunosuppressive tumor microenvironment (TME) modulation. However, one of the main issues that cause treatment failure is the poor diffusion and ... ...

Abstract	Combined cancer immunotherapy has demonstrated promising potential with an amplified antitumor response and immunosuppressive tumor microenvironment (TME) modulation. However, one of the main issues that cause treatment failure is the poor diffusion and insufficient penetration of therapeutic and immunomodulatory agents in solid tumors. Herein, a cancer treatment approach that combines photothermal therapy (PTT) and nitric oxide (NO) gas therapy for tumor extracellular matrix (ECM) degradation, along with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor that reduces tryptophan catabolism to kynurenine, and DMXAA, a stimulator of interferon gene (STING) agonist that stimulates antigen cross-presentation, is proposed to overcome this issue. Upon NIR (808 nm) laser irradiation, NO-GEL achieved the desired thermal ablation by releasing sufficient tumor antigens through immunogenic cell death (ICD). NO delivery triggered local diffusion of excess NO gas for effectively degrading tumor collagen in the ECM, homogeneously delivered NLG919 throughout the tumor tissue, inhibited IDO expression that was upregulated by PTT, and reduced the immune suppressive activities. The sustained release of DMXAA prolonged dendritic cell maturation and CD8
Language	English
Publishing date	2023-03-09
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.3c01896
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Article ; Online: Biomineralized Nanoscavenger Abrogates Proinflammatory Macrophage Polarization and Induces Neutrophil Clearance through Reverse Migration during Gouty Arthritis

Mohapatra, Adityanarayan / Rajendrakumar, Santhosh Kalash / Chandrasekaran, Gopalakrishnan / Revuri, Vishnu / Sathiyamoorthy, Padmanaban / Lee, Yong-Kyu / Lee, Jae Hyuk / Choi, Seok-Yong / Park, In-Kyu

ACS Applied Materials & Interfaces. 2023 Jan. 16, v. 15, no. 3 p.3812-3825

2023

Abstract: The deposition of monosodium urate (MSU) crystals induces the overexpression of reactive oxygen species (ROS) and proinflammatory cytokines in residential macrophages, further promoting the infiltration of inflammatory leukocytes in the joints of gouty ... ...

Abstract	The deposition of monosodium urate (MSU) crystals induces the overexpression of reactive oxygen species (ROS) and proinflammatory cytokines in residential macrophages, further promoting the infiltration of inflammatory leukocytes in the joints of gouty arthritis. Herein, a peroxidase-mimicking nanoscavenger was developed by forming manganese dioxide over albumin nanoparticles loaded with an anti-inflammatory drug, indomethacin (BIM), to block the secretion of ROS and COX2-induced proinflammatory cytokines in the MSU-induced gouty arthritis model. In the MSU-induced arthritis mouse model, the BIM nanoparticles alleviated joint swelling, which is attributed to the abrogation of ROS and inflammatory cytokine secretions from proinflammatory macrophages that induces neutrophil infiltration and fluid building up in the inflammation site. Further, the BIM nanoparticle treatment reduced the influx of macrophages and neutrophils in the injured region by blocking migration and inducing reverse migration in the zebrafish larva tail amputation model as well as in MSU-induced peritonitis and air pouch mouse models. Overall, the current strategy of employing biomineralized nanoscavengers for arthritis demonstrates clinical significance in dual blocking of peroxides and COX2 to prevent influx of inflammatory cells into the sites of inflammation.
Keywords	Danio rerio ; air ; albumins ; amputation ; arthritis ; cytokines ; indomethacin ; inflammation ; macrophages ; manganese dioxide ; mice ; models ; nanoparticles ; neutrophils ; peritonitis ; reactive oxygen species ; secretion ; tail ; nanoscavenger ; gout ; neutrophil reverse migration ; macrophage polarization: Inflammation
Language	English
Dates of publication	2023-0116
Size	p. 3812-3825.
Publishing place	American Chemical Society
Document type	Article ; Online
ISSN	1944-8252
DOI	10.1021/acsami.2c19684
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Article ; Online: Biomineralized Nanoscavenger Abrogates Proinflammatory Macrophage Polarization and Induces Neutrophil Clearance through Reverse Migration during Gouty Arthritis.

ACS applied materials & interfaces

2023 Volume 15, Issue 3, Page(s) 3812–3825

Abstract	The deposition of monosodium urate (MSU) crystals induces the overexpression of reactive oxygen species (ROS) and proinflammatory cytokines in residential macrophages, further promoting the infiltration of inflammatory leukocytes in the joints of gouty arthritis. Herein, a peroxidase-mimicking nanoscavenger was developed by forming manganese dioxide over albumin nanoparticles loaded with an anti-inflammatory drug, indomethacin (BIM), to block the secretion of ROS and COX2-induced proinflammatory cytokines in the MSU-induced gouty arthritis model. In the MSU-induced arthritis mouse model, the BIM nanoparticles alleviated joint swelling, which is attributed to the abrogation of ROS and inflammatory cytokine secretions from proinflammatory macrophages that induces neutrophil infiltration and fluid building up in the inflammation site. Further, the BIM nanoparticle treatment reduced the influx of macrophages and neutrophils in the injured region by blocking migration and inducing reverse migration in the zebrafish larva tail amputation model as well as in MSU-induced peritonitis and air pouch mouse models. Overall, the current strategy of employing biomineralized nanoscavengers for arthritis demonstrates clinical significance in dual blocking of peroxides and COX2 to prevent influx of inflammatory cells into the sites of inflammation.
MeSH term(s)	Animals ; Mice ; Arthritis, Gouty/chemically induced ; Arthritis, Gouty/drug therapy ; Neutrophils ; Reactive Oxygen Species/adverse effects ; Zebrafish ; Cyclooxygenase 2 ; Uric Acid ; Inflammation/drug therapy ; Inflammation/chemically induced ; Cytokines ; Macrophages ; Disease Models, Animal
Chemical Substances	Reactive Oxygen Species ; Cyclooxygenase 2 (EC 1.14.99.1) ; Uric Acid (268B43MJ25) ; Cytokines
Language	English
Publishing date	2023-01-16
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.2c19684
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mechanism of Action of Oxazoline-Based Antimicrobial Polymers Against Staphylococcus aureus: In Vivo Antimicrobial Activity Evaluation.

Concilio, Matilde / Garcia Maset, Ramón / Lemonche, Laia Pasquina / Kontrimas, Vito / Song, Ji-Inn / Rajendrakumar, Santhosh Kalash / Harrison, Freya / Becer, C Remzi / Perrier, Sébastien

Advanced healthcare materials

2023 Volume 12, Issue 29, Page(s) e2301961

Abstract: Antimicrobial-resistant pathogens have reached alarming levels, becoming one of the most pressing global health issues. Hence, new treatments are necessary for the fight against antimicrobial resistance. Synthetic nanoengineered antimicrobial polymers ( ... ...

Abstract	Antimicrobial-resistant pathogens have reached alarming levels, becoming one of the most pressing global health issues. Hence, new treatments are necessary for the fight against antimicrobial resistance. Synthetic nanoengineered antimicrobial polymers (SNAPs) have emerged as a promising alternative to antimicrobial peptides, overcoming some of their limitations while keeping their key features. Herein, a library of amphiphilic oxazoline-based SNAPs using cationic ring-opening polymerization (CROP) is designed. Amphipathic compounds with 70% cationic content exhibit the highest activity against clinically relevant Staphylococcus aureus isolates, maintaining good biocompatibility in vitro and in vivo. The mechanism of action of the lead compounds against S. aureus is assessed using various microscopy techniques, indicating cell membrane disruption, while the cell wall remains unaffected. Furthermore, a potential interaction of the compounds with bacterial DNA is shown, with possible implications on bacterial division. Finally, one of the compounds exhibits high efficacy in vivo in an insect infection model.
MeSH term(s)	Humans ; Staphylococcus aureus ; Polymers/pharmacology ; Anti-Infective Agents/pharmacology ; Staphylococcal Infections/drug therapy ; Staphylococcal Infections/microbiology ; Bacteria ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/chemistry ; Microbial Sensitivity Tests ; Methicillin-Resistant Staphylococcus aureus
Chemical Substances	Polymers ; Anti-Infective Agents ; Anti-Bacterial Agents
Language	English
Publishing date	2023-09-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.202301961
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Article ; Online: A sugar modified amphiphilic cationic nano-adjuvant ceased tumor immune suppression and rejuvenated peptide vaccine induced antitumor immunity in cervical cancer.

Mohapatra, Adityanarayan / Rajendrakumar, Santhosh Kalash / Cherukula, Kondareddy / Park, Myong-Suk / Padmanaban, Sathiyamoorthy / Vasukuty, Arathy / Mohanty, Ayeskanta / Lee, Jae Young / Bae, Woo Kyun / Park, In-Kyu

Biomaterials science

2023 Volume 11, Issue 5, Page(s) 1853–1866

Abstract: Human papilloma virus (HPV), one of the most common cancer-causing viruses, accounts for more than 90% of human anal and cervical cancers. Clinical studies have focused on adjuvant therapy with vaccines to improve therapeutic outcomes in patients with ... ...

Abstract	Human papilloma virus (HPV), one of the most common cancer-causing viruses, accounts for more than 90% of human anal and cervical cancers. Clinical studies have focused on adjuvant therapy with vaccines to improve therapeutic outcomes in patients with late-stage HPV-related cancers. In the present study, a mannose receptor (CD206) targeting a lithocholic acid-modified polyethylenimine (PEI) nano-adjuvant delivering the toll-like receptor 7/8 agonist, resiquimod (R848) (mLAPMi-R848), in a HPV E6- and E7-expressing TC-1 tumor murine model was developed. Peritumoral administration of mLAPMi resulted in enhanced accumulation in tumor/tumor-draining lymph nodes and significantly targeted antigen presenting cells like macrophage and dendritic cells. PEI-based nanocarriers can exploit the adjuvant potency of R848 and improve the antitumor immunity. Hence, co-administration of mLAPMi-R848 along with an E6E7 peptide in TC-1 tumor mice eradicated tumor burden and elicited splenocyte-induced cytotoxicity in TC-1 cancer cells. In a bilateral TC-1 tumor model, administration of mLAPMi-R848 and E6E7 peptide significantly suppressed both primary and secondary tumor burdens and improved the overall survival rate. Immune cell profiling revealed elevated levels of mature DCs and CD8+ T cells but reduced levels of tumor-associated immunosuppressive cells (TAICs) like myeloid derived suppressor cells (MDSCs) and regulatory T (Treg) cells in distal tumors. Overall, this study demonstrated that mLAPMi-R848 has improved the antitumor immunity of the peptide antigen against HPV-induced cancers by targeted immunodulation of antigen presenting cells (APCs) and reducing TAICs. Furthermore, this nano-adjuvant has the potential to offer a new treatment option for patients with cervical cancer and can be applied for the treatment of other HPV induced cancers.
MeSH term(s)	Female ; Humans ; Animals ; Mice ; Uterine Cervical Neoplasms/drug therapy ; Sugars ; Papillomavirus Vaccines/therapeutic use ; Papillomavirus Infections/drug therapy ; Papillomavirus Infections/prevention & control ; Papillomavirus E7 Proteins/therapeutic use ; Adjuvants, Immunologic/therapeutic use ; Peptides/therapeutic use ; Vaccines, Subunit ; Mice, Inbred C57BL
Chemical Substances	Sugars ; Papillomavirus Vaccines ; Papillomavirus E7 Proteins ; Adjuvants, Immunologic ; Peptides ; Vaccines, Subunit
Language	English
Publishing date	2023-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d2bm01715f
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Hyaluronan-coated Prussian blue nanoparticles relieve LPS-induced peritonitis by suppressing oxidative species generation in tissue-resident macrophages

Mathew, Ansuja Pulickal / Rajendrakumar, Santhosh Kalash / Mohapatra, Adityanarayan / Vasukutty, Arathy / Revuri, Vishnu / Mondal, Jagannath / Lee, Yong-Kyu / Lee, Jae Young / Park, In-Kyu

Biomaterials science. 2022 Mar. 2, v. 10, no. 5

2022

Abstract: Excessive inflammatory response during sepsis causes irreversible damage to healthy tissues and results in multi-organ failure. During infection, bacterial endotoxin-triggered inflammatory responses in macrophages facilitate the recruitment of ... ...

Abstract	Excessive inflammatory response during sepsis causes irreversible damage to healthy tissues and results in multi-organ failure. During infection, bacterial endotoxin-triggered inflammatory responses in macrophages facilitate the recruitment of circulating leukocytes, including neutrophils and monocytes. A key component that aggravates the systemic inflammatory response is the generation of stable reactive oxygen species such as hydrogen peroxide (H₂O₂). In this study, we present a versatile strategy to reduce the activation of tissue-resident macrophages and prevent leukocyte infiltration in an LPS-induced endotoxemia model. We designed and synthesized hyaluronic acid-stabilized Prussian blue (HAPB) nanoparticles and validated their activity in the dismutation of H₂O₂ in LPS-induced tissue-resident macrophages. Hyaluronic acid provided stability and enhanced the intracellular uptake of insoluble Prussian blue via the CD44 receptor on LPS-activated macrophages. Following HAPB administration to an LPS-induced peritonitis murine model, the level of M1 inflammatory macrophage population decreased, and the infiltration of neutrophils along with monocytes was suppressed. Overall, we have developed biocompatible Prussian blue nanoparticles to ameliorate inflammatory stress in LPS-induced endotoxemia by scavenging the intracellular peroxide thereby inhibiting inflammatory cascade in tissue-resident macrophages. Therefore, HAPB nanoparticles may potentially be used as novel nano-stress relievers in sepsis. The nanomaterials may have clinical application in sepsis and in other inflammatory diseases involving peroxides as key inflammatory agents.
Keywords	animal models ; biocompatible materials ; endotoxemia ; hyaluronic acid ; hydrogen peroxide ; inflammation ; macrophages ; monocytes ; neutrophils ; peritonitis
Language	English
Dates of publication	2022-0302
Size	p. 1248-1256.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d1bm01796a
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Hyaluronan-coated Prussian blue nanoparticles relieve LPS-induced peritonitis by suppressing oxidative species generation in tissue-resident macrophages.

Mathew, Ansuja Pulickal / Rajendrakumar, Santhosh Kalash / Mohapatra, Adityanarayan / Vasukutty, Arathy / Revuri, Vishnu / Mondal, Jagannath / Lee, Yong-Kyu / Lee, Jae Young / Park, In-Kyu

Biomaterials science

2022 Volume 10, Issue 5, Page(s) 1248–1256

Abstract	Excessive inflammatory response during sepsis causes irreversible damage to healthy tissues and results in multi-organ failure. During infection, bacterial endotoxin-triggered inflammatory responses in macrophages facilitate the recruitment of circulating leukocytes, including neutrophils and monocytes. A key component that aggravates the systemic inflammatory response is the generation of stable reactive oxygen species such as hydrogen peroxide (H
MeSH term(s)	Animals ; Ferrocyanides ; Hyaluronic Acid ; Hydrogen Peroxide ; Lipopolysaccharides ; Macrophages ; Mice ; Nanoparticles ; Oxidative Stress ; Peritonitis/chemically induced ; Peritonitis/drug therapy
Chemical Substances	Ferrocyanides ; Lipopolysaccharides ; Hyaluronic Acid (9004-61-9) ; Hydrogen Peroxide (BBX060AN9V) ; ferric ferrocyanide (TLE294X33A)
Language	English
Publishing date	2022-03-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d1bm01796a
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Nanoparticle-Based Phototriggered Cancer Immunotherapy and Its Domino Effect in the Tumor Microenvironment.

Rajendrakumar, Santhosh Kalash / Uthaman, Saji / Cho, Chong-Su / Park, In-Kyu

Biomacromolecules

2018 Volume 19, Issue 6, Page(s) 1869–1887

Abstract: Immune system evasion by cancer cells is one of the hallmarks of cancers, and it occurs with the support of tumor-associated immune cells (TICs) in the tumor microenvironment that increase the growth and invasiveness of tumor cells. With recent ... ...

Abstract	Immune system evasion by cancer cells is one of the hallmarks of cancers, and it occurs with the support of tumor-associated immune cells (TICs) in the tumor microenvironment that increase the growth and invasiveness of tumor cells. With recent advancements in the development of novel near-infrared (NIR)-responsive nanoparticles, specifically eradicating TICs or inducing an inflammatory immune response by activating killer T cells has become possible. This review will discuss the mechanisms and applications of phototriggered immunotherapy in detail. In addition, various nanoparticles employed in phototriggered immunotherapy for cancer treatment will be covered. Furthermore, the challenges and future directions of phototriggered nanoparticle development for anticancer immunotherapy will be briefly discussed.
MeSH term(s)	Animals ; Antineoplastic Agents, Immunological/administration & dosage ; Antineoplastic Agents, Immunological/pharmacology ; Humans ; Immunotherapy/instrumentation ; Immunotherapy/methods ; Light ; Nanoparticles/chemistry ; Nanoparticles/therapeutic use ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Photochemotherapy/instrumentation ; Photochemotherapy/methods ; Phototherapy/instrumentation ; Phototherapy/methods ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology
Chemical Substances	Antineoplastic Agents, Immunological
Language	English
Publishing date	2018-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1526-4602
ISSN (online)	1526-4602
DOI	10.1021/acs.biomac.8b00460
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Nanoparticle-Based Phototriggered Cancer Immunotherapy and Its Domino Effect in the Tumor Microenvironment

Rajendrakumar, Santhosh Kalash / Chong-Su Cho / In-Kyu Park / Saji Uthaman

Biomacromolecules. 2018 Apr. 20, v. 19, no. 6

2018

Abstract	Immune system evasion by cancer cells is one of the hallmarks of cancers, and it occurs with the support of tumor-associated immune cells (TICs) in the tumor microenvironment that increase the growth and invasiveness of tumor cells. With recent advancements in the development of novel near-infrared (NIR)-responsive nanoparticles, specifically eradicating TICs or inducing an inflammatory immune response by activating killer T cells has become possible. This review will discuss the mechanisms and applications of phototriggered immunotherapy in detail. In addition, various nanoparticles employed in phototriggered immunotherapy for cancer treatment will be covered. Furthermore, the challenges and future directions of phototriggered nanoparticle development for anticancer immunotherapy will be briefly discussed.
Keywords	immune response ; immunotherapy ; nanoparticles ; near-infrared spectroscopy ; neoplasm cells ; neoplasms ; T-lymphocytes
Language	English
Dates of publication	2018-0420
Size	p. 1869-1887.
Publishing place	American Chemical Society
Document type	Article
ISSN	1526-4602
DOI	10.1021/acs.biomac.8b00460
Database	NAL-Catalogue (AGRICOLA)

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