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Surgery-Guided Removal of Ovarian Cancer Using Up-Converting Nanoparticles

Marotta, Christopher B. and Haber, Tom and Berlin, Jacob M. and Grubbs, Robert H. (2020) Surgery-Guided Removal of Ovarian Cancer Using Up-Converting Nanoparticles. ACS Applied Materials & Interfaces, 12 (43). pp. 48371-48379. ISSN 1944-8244. https://resolver.caltech.edu/CaltechAUTHORS:20201021-121003737

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Abstract

Ovarian cancer survival and the recurrence rate are drastically affected by the amount of tumor that can be surgically removed prior to chemotherapy. Surgeons are currently limited to visual inspection, making smaller tumors difficult to be removed surgically. Enhancing the surgeon’s ability to selectively remove cancerous tissue would have a positive effect on a patient’s prognosis. One approach to aid in surgical tumor removal involves using targeted fluorescent probes to selectively label cancerous tissue. To date, there has been a trade-off in balancing two requirements for the surgeon: the ability to see maximal tumors and the ability to identify these tumors by eye while performing the surgery. The ability to see maximal tumors has been prioritized and this has led to the use of fluorophores activated by near-infrared (NIR) light as NIR penetrates most deeply in this surgical setting, but the light emitted by traditional NIR fluorophores is invisible to the naked eye. This has necessitated the use of specialty detectors and monitors that the surgeon must consult while performing the surgery. In this study, we develop nanoparticles that selectively label ovarian tumors and are activated by NIR light but emit visible light. This potentially allows for maximal tumor observation and real-time detection by eye during surgery. We designed two generations of up-converting nanoparticles that emit green light when illuminated with NIR light. These particles specifically label ovarian tumors most likely via tumor-associated macrophages, which are prominent in the tumor microenvironment. Our results demonstrate that this approach is a viable means of visualizing tumors during surgery without the need for complicated, expensive, and bulky detection equipment. Continued improvement and experimentation could expand our approach into a much needed surgical technique to aid ovarian tumor removal.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/acsami.0c14983DOIArticle
ORCID:
AuthorORCID
Berlin, Jacob M.0000-0001-7498-766X
Grubbs, Robert H.0000-0002-0057-7817
Additional Information:© 2020 American Chemical Society. Received: August 19, 2020; Accepted: October 6, 2020; Publication Date: October 20, 2020. We would like to thank Dr. Carl Blumenfeld, Dr. Michael Schultz, and Dr. William Wolf for their scientific discussions. We would like to thank Carol Garland (APhMS TEM Facility Manager), Dr. Chi Ma (Director, GPS Analytical Facility), and Professor George Rossman (GPS Division) at Caltech for their help in obtaining UCNP characterization. Fluorescent imaging was conducted at the Digital and Light Microscopy core at the City of Hope with Brian Armstrong and Loren Quintanar, and wide-field imaging was conducted at the Small Animal Imaging core at the City of Hope with Dr. David Colcher and Desiree Lasiewski. Research reported in this publication includes work performed in the Digital and Light Microscopy core and Small Animal Imaging core at the City of Hope supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. T.H. was supported by a fellowship from the Israel-City of Hope fellowship program in biomedical research. Research at Caltech was supported with funding from UCSF through the organization “Research to Prevent Blindness” under award RHG.UCNPS-1-UCSF.9566SC; Christopher B. Marotta was supported by a generous gift from Kairos Ventures Investments LLC under award RHG.KAIROS2018-1-GIFT.KAIROS2018. Research at the City of Hope was supported with funding from the NIH (grant R01 CA197359). Tom Haber was supported by a fellowship from the Israel–City of Hope fellowship program in biomedical research; research reported in this publication included work performed in cores supported by the National Cancer Institute of the NIH under Award P30 CA033572. Author Contributions: C.B.M. and T.H. contributed equally to this work and are considered co-authors. J.M.B. and R.H. Grubbs are considered co-principle investigators. The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NIHP30CA33572
Israel-City of Hope Fellowship Program in Biomedical ResearchUNSPECIFIED
Research to Prevent BlindnessRHG.UCNPS-1-UCSF.9566SC
Kairos Ventures Investments LLCRHG.KAIROS2018-1-GIFT.KAIROS2018
NIHR01 CA197359
Subject Keywords:ovarian cancer, silica coating, up-converting nanoparticles, near-IR, guided surgery, tumor removal
Issue or Number:43
Record Number:CaltechAUTHORS:20201021-121003737
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201021-121003737
Official Citation:Surgery-Guided Removal of Ovarian Cancer Using Up-Converting Nanoparticles. Christopher B. Marotta, Tom Haber, Jacob M. Berlin, and Robert H. Grubbs. ACS Applied Materials & Interfaces 2020 12 (43), 48371-48379; DOI: 10.1021/acsami.0c14983
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106184
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Oct 2020 19:33
Last Modified:20 Nov 2020 23:12

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