Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, USA.
Department of Nutrition, University of California at Davis, Davis, CA 95616, USA.
Nanomedicine (Lond). 2021 Oct;16(25):2291-2303. doi: 10.2217/nnm-2021-0080. Epub 2021 Sep 28.
To investigate a novel strategy to target tumor-associated macrophages and reprogram them to an antitumor phenotype in pancreatic adenocarcinoma (PDAC). 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. 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. M2-targeted HA-PEI/PEG nanoparticles with miR-125b can transfect tumor-associated macrophages in pancreatic tissues and may have implications for PDAC immunotherapy.
研究一种新策略，以针对肿瘤相关巨噬细胞，并将其重编程为胰腺腺癌（PDAC）中的抗肿瘤表型。将 M2 肽与 HA-PEG/HA-PEI 聚合物缀合，形成带有 miR-125b 的自组装纳米颗粒。评估 HA-PEI/PEG-M2peptide 纳米颗粒在 LSL-KrasG12D/+、LSL-Trp53R172H/+、Pdx1-Cre 基因工程小鼠胰腺肿瘤中的疗效。证明了靶向纳米制剂对 M2 巨噬细胞的特异性递送。与转染 scrambled miR 相比，腹腔内给予 M2 靶向纳米颗粒显示优先在 KPC-PDAC 小鼠的胰腺中积累，并且 M1 至 M2 巨噬细胞比率增加了四倍以上。带有 miR-125b 的 M2 靶向 HA-PEI/PEG 纳米颗粒可以转染胰腺组织中的肿瘤相关巨噬细胞，这可能对 PDAC 免疫治疗具有意义。
