Efficient Targeting of Adipose Tissue Macrophages in Obesity with Polysaccharide Nanocarriers

Liang Ma, Tzu Wen Liu, Matthew A. Wallig, Iwona T. Dobrucki, Lawrence W. Dobrucki, Erik R. Nelson, Kelly S. Swanson, Andrew M. Smith

Research output: Contribution to journalArticle

Abstract

Obesity leads to an increased risk for type 2 diabetes, heart disease, stroke, and cancer. The causal link between obesity and these pathologies has recently been identified as chronic low-grade systemic inflammation initiated by pro-inflammatory macrophages in visceral adipose tissue. Current medications based on small-molecule drugs yield significant off-target side effects with long-term use, and therefore there is a major need for targeted therapies. Here we report that nanoscale polysaccharides based on biocompatible glucose polymers can efficiently target adipose macrophages in obese mice. We synthesized a series of dextran conjugates with tunable size linked to contrast agents for positron emission tomography, fluorophores for optical microscopy, and anti-inflammatory drugs for therapeutic modulation of macrophage phenotype. We observed that larger conjugates efficiently distribute to visceral adipose tissue and selectively associate with macrophages after regional peritoneal administration. Up to 63% of the injected dose remained in visceral adipose tissue 24 h after administration, resulting in >2-fold higher local concentration compared to liver, the dominant site of uptake for most nanomedicines. Furthermore, a single-dose treatment of anti-inflammatory conjugates significantly reduced pro-inflammatory markers in adipose tissue of obese mice. Importantly, all components of these therapeutic agents are approved for clinical use. This work provides a promising nanomaterials-based delivery strategy to inhibit critical factors leading to obesity comorbidities and demonstrates a unique transport mechanism for drug delivery to visceral tissues. This approach may be further applied for high-efficiency targeting of other inflammatory diseases of visceral organs.

Original languageEnglish (US)
Pages (from-to)6952-6962
Number of pages11
JournalACS Nano
Volume10
Issue number7
DOIs
StatePublished - Jul 26 2016

Fingerprint

obesity
adipose tissues
macrophages
Macrophages
polysaccharides
Polysaccharides
Tissue
drugs
mice
delivery
heart diseases
Anti-Inflammatory Agents
dosage
phenotype
dextrans
pathology
Medical nanotechnology
strokes
liver
glucose

Keywords

  • PET
  • drug delivery
  • imaging
  • inflammation
  • nanomedicine
  • nanoparticles
  • targeting

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Efficient Targeting of Adipose Tissue Macrophages in Obesity with Polysaccharide Nanocarriers. / Ma, Liang; Liu, Tzu Wen; Wallig, Matthew A.; Dobrucki, Iwona T.; Dobrucki, Lawrence W.; Nelson, Erik R.; Swanson, Kelly S.; Smith, Andrew M.

In: ACS Nano, Vol. 10, No. 7, 26.07.2016, p. 6952-6962.

Research output: Contribution to journalArticle

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