Investigation of microsphere-mediated cellular delivery by chemical, microscopic and gene expression analysis

Lois M. Alexander, Salvatore Pernagallo, Alessandra Livigni, Rosario M. Sanchez-Martin, Joshua M. Brickman, Mark Bradley

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Amino functionalised cross-linked polystyrene microspheres of well defined sizes (0.2-2 mm) have been prepared and shown to be efficient and controllable delivery devices, capable of transporting anything from small dye molecules to bulky proteins into cells. However, the specific mechanism of cellular entry is largely unknown and widely variant from study to study. As such, chemical, biological and microscopic methods are used to elucidate the mechanism of cellular uptake for polystyrene microspheres of 0.2, 0.5 and 2 mm in mouse melanoma cells. Uptake is found to be wholly unreliant upon energetic processes, while lysosomal and endosomal tracking agents failed to show co-localisation with lysosomes/endosomes, suggesting a non-endocytic uptake pathway. To further explore the consequences of microsphere uptake, gene expression pro. ling is used to determine if there is a transcriptional response to "beadfection'' in both murine and human cells. None of the common transcriptional responses to enhanced endocytosis are observed in beadfected cells, further supporting a non-endocytic uptake mechanism. Furthermore, the microspheres are noted to have a limited interaction with cells at a transcriptional level, supporting them as a non-toxic delivery vehicle.

Original languageEnglish
Pages (from-to)399-409
Number of pages11
JournalMolecular BioSystems
Volume6
Issue number2
DOIs
Publication statusPublished - 2010

Keywords / Materials (for Non-textual outputs)

  • CLATHRIN-COATED VESICLES
  • CARBON NANOTUBES
  • CELLS
  • ENDOCYTOSIS
  • INTERNALIZATION
  • CAVEOLAE
  • CHOLESTEROL
  • MICROARRAYS
  • INHIBITION
  • MEMBRANES

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