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Tumor Microenvironment Targeting Nano–Bio Emulsion for Synergistic Combinational X‐Ray PDT with Oncolytic Bacteria Therapy
Author(s) -
Park Wooram,
Cho Soojeong,
Kang Dongkyu,
Han JunHyeok,
Park JungHoon,
Lee Byeongdu,
Lee Joonseok,
Kim DongHyun
Publication year - 2020
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201901812
Subject(s) - oncolytic virus , photodynamic therapy , cancer research , medicine , therapeutic effect , combination therapy , cancer , photosensitizer , chemistry , pharmacology , tumor cells , organic chemistry
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 NaGdF 4 :Tb,Ce@NaGdF 4 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 T 1 ‐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.