Verteporfin-Loaded Polymeric Microparticles for Intratumoral Treatment of Brain Cancer

Sagar R. Shah, Jayoung Kim, Paula Schiapparelli, Carla A. Vazquez-Ramos, Juan C. Martinez-Gutierrez, Alejandro Ruiz-Valls, Kyle Inman, James G. Shamul, Jordan J. Green, Alfredo Quinones-Hinojosa

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Glioblastoma (GBMs) is the most common and aggressive type of primary brain tumor in adults with dismal prognosis despite radical surgical resection coupled with chemo- and radiotherapy. Recent studies have proposed the use of small-molecule inhibitors, including verteporfin (VP), to target oncogenic networks in cancers. Here we report efficient encapsulation of water-insoluble VP in poly(lactic-co-glycolic acid) microparticles (PLGA MP) of ∼1.5 μm in diameter that allows tunable, sustained release. Treatment with naked VP and released VP from PLGA MP decreased cell viability of patient-derived primary GBM cells in vitro by ∼70%. Moreover, naked VP treatment significantly increased radiosensitivity of GBM cells, thereby enhancing overall tumor cell killing ability by nearly 85%. Our in vivo study demonstrated that two intratumoral administrations of sustained slow-releasing VP-loaded PLGA MPs separated by two weeks significantly attenuated tumor growth by ∼67% in tumor volume in a subcutaneous patient-derived GBM xenograft model over 26 d. Additionally, our in vitro data indicate broader utility of VP for treatment for other solid cancers, including chordoma, malignant meningioma, and various noncentral nervous system-derived carcinomas. Collectively, our work suggests that the use of VP-loaded PLGA MP may be an effective local therapeutic strategy for a variety of solid cancers, including unresectable and orphan tumors, which may decrease tumor burden and ultimately improve patient prognosis.

Original languageEnglish (US)
Pages (from-to)1433-1443
Number of pages11
JournalMolecular Pharmaceutics
Volume16
Issue number4
DOIs
StatePublished - Apr 1 2019

Keywords

  • brain cancer
  • cancer therapy
  • chordoma
  • glioblastoma
  • intratumoral treatment
  • local delivery
  • malignant meningioma
  • microparticles
  • microspheres
  • PLGA
  • poly(lactic- co-glycolic acid)
  • radiosensitization
  • verteporfin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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  • Cite this

    Shah, S. R., Kim, J., Schiapparelli, P., Vazquez-Ramos, C. A., Martinez-Gutierrez, J. C., Ruiz-Valls, A., Inman, K., Shamul, J. G., Green, J. J., & Quinones-Hinojosa, A. (2019). Verteporfin-Loaded Polymeric Microparticles for Intratumoral Treatment of Brain Cancer. Molecular Pharmaceutics, 16(4), 1433-1443. https://doi.org/10.1021/acs.molpharmaceut.8b00959