In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy
In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects, which is heavily dependent on the local conversion or activation of bioinert components. In this work, we applied a phospholipid-mimic artemisinin prodrug (ARP) for preparing an inj...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
American Association for the Advancement of Science (AAAS)
2022-01-01
|
Series: | Research |
Online Access: | https://spj.science.org/doi/10.34133/research.0003 |
_version_ | 1797227471307800576 |
---|---|
author | Yawei Du Chao Li Yu Zhang Wei Xiong Fei Wang Juan Wang Yingze Zhang Lianfu Deng Xinsong Li Wei Chen Wenguo Cui |
author_facet | Yawei Du Chao Li Yu Zhang Wei Xiong Fei Wang Juan Wang Yingze Zhang Lianfu Deng Xinsong Li Wei Chen Wenguo Cui |
author_sort | Yawei Du |
collection | DOAJ |
description | In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects, which is heavily dependent on the local conversion or activation of bioinert components. In this work, we applied a phospholipid-mimic artemisinin prodrug (ARP) for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis (RA) lesion. ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug, which can formulate “drug-in-drug” co-delivery liposomes with cargo of partner drugs (e.g., methotrexate). To further stabilize ARP/methotrexate “drug-in-drug” liposomes (MTX/ARPL) for a long-term intra-articular retention, a liposome-embedded hydrogel nano/microsphere (MTX/ARPL@MS) was prepared. After the local injection, the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously. ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation. Taken together, phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs, which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases. |
first_indexed | 2024-03-13T07:12:35Z |
format | Article |
id | doaj.art-16f271c320ff48ffbb508738ec2ee128 |
institution | Directory Open Access Journal |
issn | 2639-5274 |
language | English |
last_indexed | 2024-04-24T14:41:20Z |
publishDate | 2022-01-01 |
publisher | American Association for the Advancement of Science (AAAS) |
record_format | Article |
series | Research |
spelling | doaj.art-16f271c320ff48ffbb508738ec2ee1282024-04-02T21:01:32ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742022-01-01202210.34133/research.0003In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis TherapyYawei Du0Chao Li1Yu Zhang2Wei Xiong3Fei Wang4Juan Wang5Yingze Zhang6Lianfu Deng7Xinsong Li8Wei Chen9Wenguo Cui10Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang 050051, China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.School of Chemistry and Chemical Engineering, Southeast University, 2 Southeast University Road, Nanjing 211189, China.Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang 050051, China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects, which is heavily dependent on the local conversion or activation of bioinert components. In this work, we applied a phospholipid-mimic artemisinin prodrug (ARP) for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis (RA) lesion. ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug, which can formulate “drug-in-drug” co-delivery liposomes with cargo of partner drugs (e.g., methotrexate). To further stabilize ARP/methotrexate “drug-in-drug” liposomes (MTX/ARPL) for a long-term intra-articular retention, a liposome-embedded hydrogel nano/microsphere (MTX/ARPL@MS) was prepared. After the local injection, the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously. ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation. Taken together, phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs, which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases.https://spj.science.org/doi/10.34133/research.0003 |
spellingShingle | Yawei Du Chao Li Yu Zhang Wei Xiong Fei Wang Juan Wang Yingze Zhang Lianfu Deng Xinsong Li Wei Chen Wenguo Cui In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy Research |
title | In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy |
title_full | In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy |
title_fullStr | In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy |
title_full_unstemmed | In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy |
title_short | In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy |
title_sort | in situ activated phospholipid mimic artemisinin prodrug via injectable hydrogel nano microsphere for rheumatoid arthritis therapy |
url | https://spj.science.org/doi/10.34133/research.0003 |
work_keys_str_mv | AT yaweidu insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT chaoli insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT yuzhang insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT weixiong insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT feiwang insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT juanwang insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT yingzezhang insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT lianfudeng insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT xinsongli insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT weichen insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy AT wenguocui insituactivatedphospholipidmimicartemisininprodrugviainjectablehydrogelnanomicrosphereforrheumatoidarthritistherapy |