Hyaluronic acid nanoparticle-encapsulated microRNA-125b repolarizes tumor-associated macrophages in pancreatic cancer / Neha N Parayath, Brian V Hong, Gerardo G Mackenzie, Mansoor M Amiji
Aim:To investigate a novel strategy to target tumor-associated macrophages and reprogram them to an antitumor phenotype in pancreatic adenocarcinoma (PDAC).Methods:M2 peptides were conjugated to HA-PEG/HA-PEI polymer to form self-assembled nanoparticles with miR-125b. The efficacy of HA-PEI/PEG-M2peptide nanoparticles in pancreatic tumors from LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre genetically engineered mice was evaluated.Results:In vitroM2 macrophage-specific delivery of targeted nanoformulations was demonstrated. Intraperitoneal administration of M2-targeted nanoparticles showed preferential accumulation in the pancreas of KPC-PDAC mice and an above fourfold increase in the M1-to-M2 macrophage ratio compared with transfection with scrambled miR.Conclusion:M2-targeted HA-PEI/PEG nanoparticles with miR-125b can transfect tumor-associated macrophages in pancreatic tissues and may have implications for PDAC immunotherapy. Aim: Methods: Results: In vitro Conclusion: Lay abstract In pancreatic ductal adenocarcinoma (PDAC) tumor-associated macrophages (TAM) play a major role in tumor progression. Reprogramming of TAMs from a predominant protumoral phenotype to antitumoral phenotype is a promising strategy for PDAC. CD44 targeting hyaluronic acid-poly(ethylenimine) (HA-PEI/PEG)-based nanoparticles encapsulating miR-125b and macrophage-specific delivery and accumulation in the tumor tissue of LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre (KPC) genetically engineered mice were found. The pancreatic tumors show a switch of macrophage phenotype from protumoral to antitumoral. G12D/+ R172H/+ Graphical abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
Erscheinungsort nicht ermittelbar: 2021 |
| Enthalten in: |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Parayath, Neha N [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Themen: |
Hyaluronic acid-poly(ethylene imine) nanoparticles |
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| Umfang: |
1 Online-Ressource (13 p) |
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| doi: |
10.2217/nnm-2021-0080 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
KFL011089989 |
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| 245 | 1 | 0 | |a Hyaluronic acid nanoparticle-encapsulated microRNA-125b repolarizes tumor-associated macrophages in pancreatic cancer |c Neha N Parayath, Brian V Hong, Gerardo G Mackenzie, Mansoor M Amiji |
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| 520 | |a Aim:To investigate a novel strategy to target tumor-associated macrophages and reprogram them to an antitumor phenotype in pancreatic adenocarcinoma (PDAC).Methods:M2 peptides were conjugated to HA-PEG/HA-PEI polymer to form self-assembled nanoparticles with miR-125b. The efficacy of HA-PEI/PEG-M2peptide nanoparticles in pancreatic tumors from LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre genetically engineered mice was evaluated.Results:In vitroM2 macrophage-specific delivery of targeted nanoformulations was demonstrated. Intraperitoneal administration of M2-targeted nanoparticles showed preferential accumulation in the pancreas of KPC-PDAC mice and an above fourfold increase in the M1-to-M2 macrophage ratio compared with transfection with scrambled miR.Conclusion:M2-targeted HA-PEI/PEG nanoparticles with miR-125b can transfect tumor-associated macrophages in pancreatic tissues and may have implications for PDAC immunotherapy. Aim: Methods: Results: In vitro Conclusion: Lay abstract In pancreatic ductal adenocarcinoma (PDAC) tumor-associated macrophages (TAM) play a major role in tumor progression. Reprogramming of TAMs from a predominant protumoral phenotype to antitumoral phenotype is a promising strategy for PDAC. CD44 targeting hyaluronic acid-poly(ethylenimine) (HA-PEI/PEG)-based nanoparticles encapsulating miR-125b and macrophage-specific delivery and accumulation in the tumor tissue of LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre (KPC) genetically engineered mice were found. The pancreatic tumors show a switch of macrophage phenotype from protumoral to antitumoral. G12D/+ R172H/+ Graphical abstract | ||
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