Biodegradable nanoparticles decorated with different carbohydrates for efficient macrophage-targeted gene therapy

Qijing Chen, Mingzhu Gao, Zhongyu Li, Yue Xiao, Xin Bai, Kofi Oti Boakye-Yiadom, Xiaoyang Xu, Xue Qing Zhang

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Macrophages are attractive therapeutic targets due to their contributions to many pathological processes including cancers, atherosclerosis, obesity, diabetes and other inflammatory diseases. Macrophage-targeted gene therapy is an effective strategy for regulating macrophage function at the site of inflammation to treat related diseases. However, macrophages are recognized as difficult to transfect cells and non-specific delivery would inevitably cause unwanted systemic side effects. Herein, we prepared a series of macrophage-targeted nanoparticles (NPs) using cationic lipid-like compound G0-C14 and different carbohydrates-modified poly(lactide-co-glycolide) (PLGA) or poly(lactide-coglycolide)-b-poly(ethylene glycol) (PLGA-PEG) for gene delivery by a robust self-assembly method. The yielded NPs were decorated with carbohydrate-based targeting moieties including mannose, galactose, dextran, and a mixture of mannose and galactose. EGFP messenger RNA (mRNA) and GFP plasmid DNA (pDNA) were used as reporter genes to evaluate NP-mediated gene transfection in macrophages. Experimental results of macrophage phagocytosis demonstrated that more carbohydrate-decorated NPs were endocytosed by Raw 264.7 cells than the ones without carbohydrate modification. Mannose-decorated NPs showed better targeting ability to macrophages than NPs decorated with galactose only and a blended mixture of mannose and galactose. It is worth noting that polysaccharide dextran-modified NPs also exhibited evident targeting effects. CCK-8 assay revealed that no cytotoxicity was observed for all tested NP concentrations up to 2.8 mg/mL. The carbohydrate-decorated polymer/G0-C14 exhibited strong entrapment of mRNA and pDNA with an encapsulation efficiency of above 95%. The targeted NPs significantly improved cellular internalization and transfection efficiency in macrophages, depending on the type and content of the carbohydrate moieties presented on the NP surface. Interestingly, dextran-decorated NPs showing higher endocytosis at various concentrations in macrophages also demonstrated more efficient mRNA transfection, suggesting that the NP-mediated mRNA transfection efficiency was consistent with the endocytosis results.

Original languageEnglish (US)
Pages (from-to)179-190
Number of pages12
JournalJournal of Controlled Release
Volume323
DOIs
StatePublished - Jul 10 2020

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Carbohydrate decoration
  • Gene delivery
  • Macrophage-targeting nanoparticles (NPs)
  • Nanomedicine

Fingerprint

Dive into the research topics of 'Biodegradable nanoparticles decorated with different carbohydrates for efficient macrophage-targeted gene therapy'. Together they form a unique fingerprint.

Cite this