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Intrinsic and Stable Conjugation of Thiolated Mesoporous Silica Nanoparticles with Radioarsenic

Journal Article · · ACS Applied Materials and Interfaces
 [1];  [2];  [3];  [4];  [4];  [4];  [5]
  1. Univ. of Wisconsin, Madison, WI (United States). School of Medicine and Public Health and Dept. of Medical Physics; OSTI
  2. Univ. of Wisconsin, Madison, WI (United States). School of Medicine and Public Health and Dept. of Radiology; Memorial Sloan Kettering Cancer Center, New York City, NY (United States)
  3. Univ. of Wisconsin, Madison, WI (United States). Materials Science Program
  4. Univ. of Wisconsin, Madison, WI (United States). School of Medicine and Public Health and Dept. of Medical Physics
  5. Univ. of Wisconsin, Madison, WI (United States). School of Medicine and Public Health, Dept. of Medical Physics, Dept. of Radiology, Materials Science Program and Carbone Cancer Center
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 of chemotherapeutic quantities of the drug. In conclusion, these results show the great potential of radioarsenic-labeled thiolated MSN for the preparation of theranostic radiopharmaceuticals and image-guided drug delivery of ATO-based chemotherapeutics.
Research Organization:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Organization:
American Cancer Society (ACS); National Inst. of Health (NIH); USDOE
Grant/Contract Number:
SC0005281; SC0008384
OSTI ID:
1463090
Journal Information:
ACS Applied Materials and Interfaces, Journal Name: ACS Applied Materials and Interfaces Journal Issue: 8 Vol. 9; ISSN 1944-8244
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English

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