Multivalent niacin nanoconjugates for delivery to cytoplasmic lipid droplets

Anjali Sharma, Armen Khatchadourian, Kunal Khanna, Rishi Sharma, Ashok Kakkar, Dusica Maysinger

Research output: Contribution to journalArticle

Abstract

We report here the design, synthesis, and properties, of multifunctional niacin nanoconjugates based on dendritic, miktoarm and linear backbone nanocarriers, using "click" chemistry. The conjugates were in this instance used to deliver the therapeutic agent niacin to lipid droplets. The desired combination of niacin, a lipophilic fluorescent dye (BODIPY), and polyethylene glycol (PEG), was achieved by covalently linking the desired agents to the selected carrier. The nanocarriers containing niacin and BODIPY were found almost exclusively within cytoplasmic lipid droplets in the cells used in this study (living hepatocytes and microglia), whereas the trifunctional carrier containing niacin, BODIPY and PEG was partially localized within these organelles but also elsewhere in the cytoplasmic compartment. Spectrofluorometric analyses, confocal microscopy and fluorescence cell sorting revealed different rates and extent of multifunctional conjugate(s) internalization in the two cell types. Even micromolar concentrations of the internalized multifunctional conjugates did not cause significant cell death or mitochondrial functional impairment, suggesting that they are suitable candidate nanostructures for lipid droplet imaging and for targeting drugs to these cellular organelles. These studies provide an efficient and easy way to synthesize multifunctional nanocarriers by click chemistry, applicable to the synthesis of related multifunctional nanostructures and to their use in the targeting of cellular organelles, including lipid droplets.

Original languageEnglish (US)
Pages (from-to)1419-1429
Number of pages11
JournalBiomaterials
Volume32
Issue number5
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

Keywords

  • Dendrimers
  • Drug delivery
  • Multifunctional nanocarriers
  • Niacin
  • Targeting lipid droplets

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Sharma, A., Khatchadourian, A., Khanna, K., Sharma, R., Kakkar, A., & Maysinger, D. (2011). Multivalent niacin nanoconjugates for delivery to cytoplasmic lipid droplets. Biomaterials, 32(5), 1419-1429. https://doi.org/10.1016/j.biomaterials.2010.10.025