Low‐Cost, High‐Pressure‐Synthesized Oxygen‐Entrapping Materials to Improve Treatment of Solid Tumors

Author:

Bi Jianling123,Witt Emily123,Voltarelli Vanessa A.4,Feig Vivian R.567,Venkatachalam Veena89,Boyce Hannah10,McGovern Megan12,Gutierrez Wade R.311ORCID,Rytlewski Jeffrey D.312,Bowman Kate R.1,Rhodes Ashley C.12,Cook Austin N.12,Muller Benjamin N.57,Smith Matthew G.13,Ramos Alexis Rebecca313,Panchal Heena13,Dodd Rebecca D.312,Henry Michael D.1314,Mailloux Adam3,Traverso Giovanni567,Otterbein Leo E.4,Byrne James D.123ORCID

Affiliation:

1. Department of Radiation Oncology University of Iowa 200 Hawkins Drive Iowa City IA 52242 USA

2. Department of Biomedical Engineering University of Iowa 200 Hawkins Drive Iowa City IA 52242 USA

3. Holden Comprehensive Cancer Center University of Iowa Iowa City IA 52242 USA

4. Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School 3 Blackfan Circle Boston MA 02215 USA

5. Division of Gastroenterology Brigham and Women's Hospital Harvard Medical School 75 Francis St. Boston MA 02115 USA

6. David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology 500 Main St Building 76 Cambridge MA 02142 USA

7. Department of Mechanical Engineering Massachusetts Institute of Technology 77 Massachusetts Ave Cambridge MA 02139 USA

8. Department of Systems Biology Harvard Medical School 75 Francis St. Boston MA 02115 USA

9. Department of Radiation Oncology Brigham and Women's Hospital Harvard Medical School 75 Francis St. Boston MA 02115 USA

10. Department of Chemical Engineering Massachusetts Institute of Technology 25 Ames St. Cambridge MA 02139 USA

11. Medical Scientist Training Program University of Iowa Iowa City IA 52242 USA

12. Department of Internal Medicine University of Iowa Iowa City IA 52242 USA

13. Department of Microbiology and Immunology Carver College of Medicine University of Iowa Iowa City IA 52242 USA

14. Department of Molecular Physiology and Biophysics Carver College of Medicine University of Iowa Iowa City IA 52242 USA

Abstract

AbstractTumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric oxygen therapy and microbubble infusion, are utilized to improve the responses to current standard‐of‐care therapies. However, key obstacles remain, in particular delivery of oxygen at the appropriate dose and with optimal pharmacokinetics. Toward overcoming these hurdles, gas‐entrapping materials (GeMs) that are capable of tunable oxygen release are formulated. It is shown that injection or implantation of these materials into tumors can mitigate tumor hypoxia by delivering oxygen locally and that these GeMs enhance responsiveness to radiation and chemotherapy in multiple tumor types. This paper also demonstrates, by comparing an oxygen (O2)‐GeM to a sham GeM, that the former generates an antitumorigenic and immunogenic tumor microenvironment in malignant peripheral nerve sheath tumors. Collectively the results indicate that the use of O2‐GeMs is promising as an adjunctive strategy for the treatment of solid tumors.

Funder

Holden Comprehensive Cancer Center, University of Iowa

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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