Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery

Zhiwei Xie, Yixue Su, Gloria B. Kim, Erhan Selvi, Chuying Ma, Virginia Aragon-Sanabria, Jer Tsong Hsieh, Cheng Dong, Jian Yang

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell-mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer-specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP-PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti-BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP-PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP-PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell–cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The “self-powered” immune cell-mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.

Original languageEnglish (US)
Article number1603121
JournalSmall
Volume13
Issue number10
DOIs
StatePublished - Mar 14 2017

Keywords

  • drug delivery
  • immune cells
  • melanoma
  • nanoparticles
  • theranostics

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)
  • Engineering (miscellaneous)

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  • Cite this

    Xie, Z., Su, Y., Kim, G. B., Selvi, E., Ma, C., Aragon-Sanabria, V., Hsieh, J. T., Dong, C., & Yang, J. (2017). Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery. Small, 13(10), [1603121]. https://doi.org/10.1002/smll.201603121