Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 9, Issue 8, Pages 6772-6781Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b14049
Keywords
image-guided drug delivery; arsenic trioxide; radioarsenic; positron emission tomography; As-72; As-76; As-77; radiolabeling
Funding
- University of Wisconsin Madison
- U.S. Department of Energy [DE-SC0005281, DE-SC0008384]
- National Institutes of Health [T32CA009206, 1R0-1CA169365]
- American Cancer Society [125246-RSG-13-099-01-CCE]
- University of Wisconsin Carbone Cancer Center [P30 CA014520]
- U.S. Department of Energy (DOE) [DE-SC0005281] Funding Source: U.S. Department of Energy (DOE)
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The development of new image-guided drug delivery tools to improve the therapeutic efficacy of chemotherapeutics remains an important goal in nanomedicine. Using labeling strategies that involve radioelements that have theranostic pairs of diagnostic positron-emitting isotopes and therapeutic electron-emitting isotopes has promise in achieving this goal and further enhancing drug performance through radiotherapeutic effects. The isotopes of radioarsenic offer such theranostic potential and would allow for the use of positron emission tomography (PET) for image-guided drug delivery studies of the arsenic-based chemotherapeutic arsenic trioxide (ATO). Thiolated mesoporous silica nanoparticles (MSN) are shown to effectively and stably bind cyclotron-produced radioarsenic. Labeling studies elucidate that this affinity is a result of specific binding between trivalent arsenic and nanoparticle thiol surface modification. Serial PET imaging of the in vivo murine biodistribution of radiolabeled Silica nanoparticles shows very good stability toward dearsenylation that is directly proportional to silica porosity. Thiolated MSNs are found to have a macroscopic arsenic loading capacity of 20 mg of ATO per gram of MSN, sufficient for delivery
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