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231226s2024 xx |||||o 00| ||eng c |
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|a 10.1002/adma.202302292
|2 doi
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|a pubmed25n1196.xml
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|a eng
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|a Qin, Yating
|e verfasserin
|4 aut
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| 245 |
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|a High-Throughput Screening of Surface Engineered Cyanine Nanodots for Active Transport of Therapeutic Antibodies into Solid Tumor
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|c 2024
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|a Text
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|a ƒaComputermedien
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|a ƒa Online-Ressource
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|a Date Completed 04.03.2024
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|a Date Revised 04.03.2024
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2023 Wiley-VCH GmbH.
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|a The successful delivery of therapeutic biomacromolecules into solid tumor holds great challenge due to their high resistance to penetrate through the complex tumor microenvironments. Here, active-transporting nanoparticles are harnessed to efficiently deliver biomacromolecular drugs into solid tumors through cell transcytosis. A series of molecularly precise cyanine 5-cored polylysine G5 dendrimers (Cy5 nanodots) with different peripheral amino acids (G5-AA) is prepared. The capability of these positively charged nanodots to induce cell endocytosis, exocytosis, and transcytosis is evaluated via fluorescence-based high-throughput screen. The optimized nanodots (G5-R) are conjugated with αPD-L1 (a therapeutic monoclonal antibody binding to programmed-death ligand 1) (αPD-L1-G5-R) to demonstrate the nanoparticle-mediated tumor active transport. The αPD-L1-G5-R can greatly enhance the tumor-penetration capability through adsorption-mediated transcytosis (AMT). The effectiveness of αPD-L1-G5-R is tested in treating mice bearing partially resected CT26 tumors, mimicking the local immunotherapy of residual tumors post-surgery in clinic. The αPD-L1-G5-R embedded in fibrin gel can efficiently mediate tumor cell transcytosis, and deliver αPD-L1 throughout the tumor, thereby enhancing immune checkpoint blockade, reducing tumor recurrence, and significantly prolonging the survival time. The active-transporting nanodots are promising platforms for efficient tumor delivery of therapeutic biomacromolecules
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|a Journal Article
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4 |
|a active-transporting nanocarriers
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4 |
|a dye-cored dendrimers
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| 650 |
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4 |
|a fluorescent nanodots
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| 650 |
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4 |
|a immune checkpoint blockade
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| 650 |
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4 |
|a protein drug delivery
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| 650 |
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4 |
|a transcytosis
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| 650 |
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4 |
|a tumor penetration
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| 650 |
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7 |
|a Amino Acids
|2 NLM
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| 700 |
1 |
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|a Wang, Guowei
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chen, Linying
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Sun, Yuji
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yang, Jiajia
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Piao, Ying
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Shen, Youqing
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhou, Zhuxian
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
|d 1998
|g 36(2024), 9 vom: 01. März, Seite e2302292
|w (DE-627)NLM098206397
|x 1521-4095
|7 nnas
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| 773 |
1 |
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|g volume:36
|g year:2024
|g number:9
|g day:01
|g month:03
|g pages:e2302292
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|u http://dx.doi.org/10.1002/adma.202302292
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