Tumor Microenvironment Targeting Nano–Bio Emulsion for Synergistic Combinational X-Ray PDT with Oncolytic Bacteria Therapy

Wooram Park, Soojeong Cho, Dongkyu Kang, Jun Hyeok Han, Jung Hoon Park, Byeongdu Lee, Joonseok Lee, Dong Hyun Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Various cancer therapies have been developed, but tumor recurrence with incomplete tumor killing and remaining tumor cells/tissues is frequent in monotherapies. Herein, a nano–bio therapeutic emulsion formulated with multifunctional nanoscintillators and anaerobic Clostridium novyi-NT spores for synergistic image-guided combinational cancer therapy is reported. MRI visible nanoscintillators (NSs) are synthesized with a NaGdF4:Tb,Ce@NaGdF4 core/shell structure for an image-guided X-ray photodynamic therapy (PDT) of the normoxic peripheral tumor. An anaerobic oncolytic bacterium (C. novyi-NT) therapy is combined to treat the hypoxic central tumor tissues. Photosensitizer-coated NSs (PS-NSs) and C. novyi-NT spores are emulsified with clinically available ethiodized oil (Lipiodol) to be the nano–bio therapeutic emulsion and injected into the tumor with computed tomography image guidance. The distribution of nano–bio therapeutic emulsion, including PS-NSs and anaerobic C. novyi-NT spores in the tumor site, is confirmed by both X-ray and T1-weighted magnetic resonance imaging. Following the image-guided X-ray PDT and anaerobic C. novyi- NT combination treatment, apoptotic cell death in cancer tissues, including both peripheral and central tumor regions, is significantly higher than in the control groups. This combination therapy approach using a nano–bio therapeutic emulsion is expected to overcome the limitations of conventional cancer therapy, resulting in increased cancer-therapeutic efficacy.

Original languageEnglish (US)
Article number1901812
JournalAdvanced Healthcare Materials
Volume9
Issue number13
DOIs
StatePublished - Jul 1 2020

Keywords

  • X-ray photodynamic therapy (PDT)
  • bacteriolytic therapy
  • nano–bio emulsions
  • scintillating nanoparticles
  • tumor microenvironments

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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