Hyaluronic acid nanoparticle-encapsulated microRNA-125b repolarizes tumor-associated macrophages in pancreatic cancer

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 vitro M2 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

Nanomedicine (London, England) - 16(2021), 25 vom: 04. Okt., Seite 2291-2303

Sprache:

Englisch

Beteiligte Personen:

Parayath, Neha N [VerfasserIn]
Hong, Brian V [VerfasserIn]
Mackenzie, Gerardo G [VerfasserIn]
Amiji, Mansoor M [VerfasserIn]

Links:

Volltext

Themen:

9004-61-9
Hyaluronic Acid
Hyaluronic acid-poly(ethylene imine) nanoparticles
Intraperitoneal administration
Journal Article
KPC mice
MicroRNA transfection
MicroRNAs
Mirn125 microRNA, mouse
Pancreatic adenocarcinoma
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Tumor-associated macrophages

Anmerkungen:

Date Completed 07.10.2021

Date Revised 03.10.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.2217/nnm-2021-0080

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM331211572