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

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

doi:10.1002/adhm.201901812

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

Journal Article · Thu Jun 11 00:00:00 EDT 2020 · Advanced Healthcare Materials

DOI:https://doi.org/10.1002/adhm.201901812· OSTI ID:1774585

Park, Wooram ^[1]; Cho, Soojeong ^[2]; Kang, Dongkyu ^[3]; Han, Jun‐Hyeok ^[4]; Park, Jung‐Hoon ^[5]; Lee, Byeongdu ^[6]; Lee, Joonseok ^[7]; ^[8]

Northwestern University, Chicago, IL (United States); The Catholic University of Korea, Gyeonggi (South Korea)
Northwestern University, Chicago, IL (United States)
Korea Institute of Science and Technology (KIST), Seoul (South Korea)
The Catholic University of Korea, Gyeonggi (South Korea)
Biomedical Engineering Research Center, Seoul (South Korea)
Argonne National Lab. (ANL), Argonne, IL (United States)
Korea Institute of Science and Technology (KIST), Seoul (South Korea); Hanyang Unic., Seoul (South Korea)
Northwestern University, Chicago, IL (United States); Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States); McCormick School of Engineering, Evanston, IL (United States)

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. Finally, 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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH); Korea Institute of Science and Technology (KIST)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1774585

Journal Information:: Advanced Healthcare Materials, Journal Name: Advanced Healthcare Materials Journal Issue: 13 Vol. 9; ISSN 2192-2640

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

References (50)

Temperature-Sensitive Magnetic Drug Carriers for Concurrent Gemcitabine Chemohyperthermia Kim, Dong-Hyun; Guo, Yang; Zhang, Zhuoli Advanced Healthcare Materials, Vol. 3, Issue 5 https://doi.org/10.1002/adhm.201300209	journal	October 2013
Designing Multi-Branched Gold Nanoechinus for NIR Light Activated Dual Modal Photodynamic and Photothermal Therapy in the Second Biological Window Vijayaraghavan, Priya; Liu, Cheng-Hong; Vankayala, Raviraj Advanced Materials, Vol. 26, Issue 39 https://doi.org/10.1002/adma.201400703	journal	July 2014
Self-Assembled Peptide- and Protein-Based Nanomaterials for Antitumor Photodynamic and Photothermal Therapy Abbas, Manzar; Zou, Qianli; Li, Shukun Advanced Materials, Vol. 29, Issue 12 https://doi.org/10.1002/adma.201605021	journal	January 2017
Responsive Assembly of Upconversion Nanoparticles for pH‐Activated and Near‐Infrared‐Triggered Photodynamic Therapy of Deep Tumors Li, Fangyuan; Du, Yang; Liu, Jianan Advanced Materials, Vol. 30, Issue 35 https://doi.org/10.1002/adma.201802808	journal	July 2018
Chemophototherapy: An Emerging Treatment Option for Solid Tumors Luo, Dandan; Carter, Kevin A.; Miranda, Dyego Advanced Science, Vol. 4, Issue 1 https://doi.org/10.1002/advs.201600106	journal	May 2016
Marriage of Scintillator and Semiconductor for Synchronous Radiotherapy and Deep Photodynamic Therapy with Diminished Oxygen Dependence Zhang, Chen; Zhao, Kuaile; Bu, Wenbo Angewandte Chemie International Edition, Vol. 54, Issue 6 https://doi.org/10.1002/anie.201408472	journal	December 2014
Designing Upconversion Nanocrystals Capable of 745 nm Sensitization and 803 nm Emission for Deep-Tissue Imaging Liang, Liangliang; Xie, Xiaoji; Loong, Daniel Teh Boon Chemistry - A European Journal, Vol. 22, Issue 31 https://doi.org/10.1002/chem.201602514	journal	June 2016
Branched Gold Nanoparticle Coating of Clostridium novyi -NT Spores for CT-Guided Intratumoral Injection Park, Wooram; Cho, Soojeong; Huang, Xiaoke Small, Vol. 13, Issue 5 https://doi.org/10.1002/smll.201602722	journal	November 2016
Rattle-Structured Upconversion Nanoparticles for Near-IR-Induced Suppression of Alzheimer's β-Amyloid Aggregation Kuk, Sukeun; Lee, Byung Il; Lee, Joon Seok Small, Vol. 13, Issue 11 https://doi.org/10.1002/smll.201603139	journal	January 2017
Paramagnetic inorganic nanoparticles as T ₁ MRI contrast agents: Paramagnetic nanoparticles as MRI contrast agents Lee, Soo Hong; Kim, Byung Hyo; Na, Hyon Bin Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, Vol. 6, Issue 2 https://doi.org/10.1002/wnan.1243	journal	October 2013
Development of pumping emulsification device with glass membrane to form ideal lipiodol emulsion in transarterial chemoembolization Tanaka, Toshihiro; Masada, Tetsuya; Nishiofuku, Hideyuki European Radiology, Vol. 28, Issue 5 https://doi.org/10.1007/s00330-017-5197-x	journal	December 2017
Detection of superoxide anion radical in phospholipid liposomal membrane by fluorescence quenching method using 1,3-diphenylisobenzofuran Ohyashiki, Takao; Nunomura, Masaki; Katoh, Takafumi Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1421, Issue 1 https://doi.org/10.1016/S0005-2736(99)00119-4	journal	September 1999
Doxorubicin loaded singlet-oxygen producible polymeric micelle based on chlorine e6 conjugated pluronic F127 for overcoming drug resistance in cancer Park, Hyung; Park, Wooram; Na, Kun Biomaterials, Vol. 35, Issue 27 https://doi.org/10.1016/j.biomaterials.2014.05.063	journal	September 2014
Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer Jeon, Min Jeong; Gordon, Andrew C.; Larson, Andrew C. Biomaterials, Vol. 88 https://doi.org/10.1016/j.biomaterials.2016.02.021	journal	May 2016
Targeted multimodal nano-reporters for pre-procedural MRI and intra-operative image-guidance Lee, Joonseok; Gordon, Andrew C.; Kim, Hacksung Biomaterials, Vol. 109 https://doi.org/10.1016/j.biomaterials.2016.09.013	journal	December 2016
Synthesis of surface amino-functionalized NaGdF4:Ce,Tb nanoparticles and their luminescence resonance energy transfer (LRET) with Au nanoparticles Mi, Congcong; Gao, Huanyu; Li, Feng Colloids and Surfaces A: Physicochemical and Engineering Aspects, Vol. 395 https://doi.org/10.1016/j.colsurfa.2011.12.022	journal	February 2012
Clostridium novyi-NT in cancer therapy Staedtke, Verena; Roberts, Nicholas J.; Bai, Ren-Yuan Genes & Diseases, Vol. 3, Issue 2 https://doi.org/10.1016/j.gendis.2016.01.003	journal	June 2016
Fluorescence probes used for detection of reactive oxygen species Gomes, Ana; Fernandes, Eduarda; Lima, José L. F. C. Journal of Biochemical and Biophysical Methods, Vol. 65, Issue 2-3 https://doi.org/10.1016/j.jbbm.2005.10.003	journal	December 2005
Lipiodol-based emulsions used for transarterial chemoembolization and drug delivery: Effects of composition on stability and product quality Ahnfelt, Emelie; Degerstedt, Oliver; Lilienberg, Elsa Journal of Drug Delivery Science and Technology, Vol. 53 https://doi.org/10.1016/j.jddst.2019.101143	journal	October 2019
Chemoembolization of hepatocellular carcinoma with drug eluting beads: Efficacy and doxorubicin pharmacokinetics Varela, María; Real, María Isabel; Burrel, Marta Journal of Hepatology, Vol. 46, Issue 3 https://doi.org/10.1016/j.jhep.2006.10.020	journal	March 2007
Autofluorescence-Free Immunoassay Using X-ray Scintillating Nanotags Ou, Xiang-Yu; Guo, Tao; Song, Liang Analytical Chemistry, Vol. 90, Issue 11 https://doi.org/10.1021/acs.analchem.8b01315	journal	April 2018
NaCeF ₄ :Gd,Tb Scintillator as an X-ray Responsive Photosensitizer for Multimodal Imaging-Guided Synchronous Radio/Radiodynamic Therapy Zhong, Xiaoyan; Wang, Xianwen; Zhan, Guiting Nano Letters, Vol. 19, Issue 11 https://doi.org/10.1021/acs.nanolett.9b03682	journal	September 2019
Photosensitizer-Conjugated Hyaluronic Acid-Shielded Polydopamine Nanoparticles for Targeted Photomediated Tumor Therapy Han, Jieun; Park, Wooram; Park, Sin-jung ACS Applied Materials & Interfaces, Vol. 8, Issue 12 https://doi.org/10.1021/acsami.6b01664	journal	March 2016
Photoperiodic Flower Mimicking Metallic Nanoparticles for Image-Guided Medicine Applications Cho, Soojeong; Lee, Byeongdu; Park, Wooram ACS Applied Materials & Interfaces, Vol. 10, Issue 33 https://doi.org/10.1021/acsami.8b09596	journal	July 2018
Near-Infrared-Triggered Photodynamic Therapy with Multitasking Upconversion Nanoparticles in Combination with Checkpoint Blockade for Immunotherapy of Colorectal Cancer Xu, Jun; Xu, Ligeng; Wang, Chenya ACS Nano, Vol. 11, Issue 5 https://doi.org/10.1021/acsnano.7b00715	journal	April 2017
Intermolecular Structural Change for Thermoswitchable Polymeric Photosensitizer Park, Wooram; Park, Sin-Jung; Cho, Soojeong Journal of the American Chemical Society, Vol. 138, Issue 34 https://doi.org/10.1021/jacs.6b04875	journal	August 2016
Chlorin-Based Nanoscale Metal–Organic Framework Systemically Rejects Colorectal Cancers via Synergistic Photodynamic Therapy and Checkpoint Blockade Immunotherapy Lu, Kuangda; He, Chunbai; Guo, Nining Journal of the American Chemical Society, Vol. 138, Issue 38 https://doi.org/10.1021/jacs.6b06663	journal	September 2016
Tunable Narrow Band Emissions from Dye-Sensitized Core/Shell/Shell Nanocrystals in the Second Near-Infrared Biological Window Shao, Wei; Chen, Guanying; Kuzmin, Andrey Journal of the American Chemical Society, Vol. 138, Issue 50 https://doi.org/10.1021/jacs.6b08973	journal	December 2016
Self-Assembled Core–Shell Nanoparticles for Combined Chemotherapy and Photodynamic Therapy of Resistant Head and Neck Cancers He, Chunbai; Liu, Demin; Lin, Wenbin ACS Nano, Vol. 9, Issue 1 https://doi.org/10.1021/nn506963h	journal	January 2015
Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice Gil, M.; Bieniasz, M.; Seshadri, M. British Journal of Cancer, Vol. 105, Issue 10 https://doi.org/10.1038/bjc.2011.429	journal	October 2011
The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT Bettegowda, Chetan; Huang, Xin; Lin, Jimmy Nature Biotechnology, Vol. 24, Issue 12 https://doi.org/10.1038/nbt1256	journal	November 2006
Photodynamic therapy for cancer Dolmans, Dennis E. J. G. J.; Fukumura, Dai; Jain, Rakesh K. Nature Reviews Cancer, Vol. 3, Issue 5 https://doi.org/10.1038/nrc1071	journal	May 2003
Photodynamic therapy and anti-tumour immunity Castano, Ana P.; Mroz, Pawel; Hamblin, Michael R. Nature Reviews Cancer, Vol. 6, Issue 7 https://doi.org/10.1038/nrc1894	journal	July 2006
A novel deep photodynamic therapy modality combined with CT imaging established via X-ray stimulated silica-modified lanthanide scintillating nanoparticles Elmenoufy, Ahmed H.; Tang, Yong'an; Hu, Jun Chemical Communications, Vol. 51, Issue 61 https://doi.org/10.1039/C5CC04135J	journal	January 2015
Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy Zhou, Zijian; Song, Jibin; Nie, Liming Chemical Society Reviews, Vol. 45, Issue 23 https://doi.org/10.1039/C6CS00271D	journal	January 2016
Advanced smart-photosensitizers for more effective cancer treatment Park, Wooram; Cho, Soojeong; Han, Jieun Biomaterials Science, Vol. 6, Issue 1 https://doi.org/10.1039/C7BM00872D	journal	January 2018
Engineering gold-based radiosensitizers for cancer radiotherapy Goswami, Nirmal; Luo, Zhentao; Yuan, Xun Materials Horizons, Vol. 4, Issue 5 https://doi.org/10.1039/C7MH00451F	journal	January 2017
Near-infrared light triggered photothermal therapy and enhanced photodynamic therapy with a tumor-targeting hydrogen peroxide shuttle Wang, Bing; Lin, Weiming; Mao, Zhengwei Journal of Materials Chemistry B, Vol. 6, Issue 19 https://doi.org/10.1039/C8TB00476E	journal	January 2018
Bacteriolytic therapy can generate a potent immune response against experimental tumors Agrawal, N.; Bettegowda, C.; Cheong, I. Proceedings of the National Academy of Sciences, Vol. 101, Issue 42 https://doi.org/10.1073/pnas.0406242101	journal	October 2004
Exceedingly small iron oxide nanoparticles as positive MRI contrast agents Wei, He; Bruns, Oliver T.; Kaul, Michael G. Proceedings of the National Academy of Sciences, Vol. 114, Issue 9 https://doi.org/10.1073/pnas.1620145114	journal	February 2017
Combination bacteriolytic therapy for the treatment of experimental tumors Dang, L. H.; Bettegowda, C.; Huso, D. L. Proceedings of the National Academy of Sciences, Vol. 98, Issue 26 https://doi.org/10.1073/pnas.251543698	journal	November 2001
Long-Term Results of Lipiodol-Transcatheter Arterial Embolization With Cisplatin or Doxorubicin for Unresectable Hepatocellular Carcinoma Ono, Yukihiko; Yoshimasu, Takayuki; Ashikaga, Ryuichiro American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 23, Issue 6 https://doi.org/10.1097/00000421-200012000-00006	journal	January 2000
A randomized controlled trial of transcatheter arterial chemoembolization with lipiodol, doxorubicin and cisplatin versus intravenous doxorubicin for patients with unresectable hepatocellular carcinoma Mabed, M.; Esmaeel, M.; El-Khodary, T. European Journal of Cancer Care, Vol. 18, Issue 5 https://doi.org/10.1111/j.1365-2354.2008.00984.x	journal	September 2009
First-in-Human Study Testing a New Radioenhancer Using Nanoparticles (NBTXR3) Activated by Radiation Therapy in Patients with Locally Advanced Soft Tissue Sarcomas Bonvalot, Sylvie; Le Pechoux, Cécile; De Baere, Thierry Clinical Cancer Research, Vol. 23, Issue 4 https://doi.org/10.1158/1078-0432.CCR-16-1297	journal	October 2016
TUNEL Apoptotic Cell Detection in Tissue Sections: Critical Evaluation and Improvement Labat-Moleur, Françoise; Guillermet, Christiane; Lorimier, Philippe Journal of Histochemistry & Cytochemistry, Vol. 46, Issue 3 https://doi.org/10.1177/002215549804600306	journal	March 1998
Integrin αvβ3 and CD44 pathways in metastatic prostate cancer cells support osteoclastogenesis via a Runx2/Smad 5/receptor activator of NF-κB ligand signaling axis Gupta, Aditi; Cao, Wei; Chellaiah, Meenakshi A. Molecular Cancer, Vol. 11, Issue 1 https://doi.org/10.1186/1476-4598-11-66	journal	January 2012
Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells Desai, Bhavik; Rogers, Michael J.; Chellaiah, Meenakshi A. Molecular Cancer, Vol. 6, Issue 1 https://doi.org/10.1186/1476-4598-6-18	journal	January 2007
Intratumor Administration of the Photosensitizer Pc 4 Affords Photodynamic Therapy Efficacy and Selectivity at Short Drug-Light Intervals Foster, Thomas H.; Giesselman, Benjamin R.; Hu, Rui Translational Oncology, Vol. 3, Issue 2 https://doi.org/10.1593/tlo.09295	journal	April 2010
Multi-watt near-infrared light therapy as a neuroregenerative treatment for traumatic brain injury Henderson, TheodoreA Neural Regeneration Research, Vol. 11, Issue 4 https://doi.org/10.4103/1673-5374.180737	journal	January 2016
X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy Wang, Geoffrey D.; Nguyen, Ha T.; Chen, Hongmin Theranostics, Vol. 6, Issue 13 https://doi.org/10.7150/thno.16141	journal	January 2016

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