Intrinsic and Stable Conjugation of Thiolated Mesoporous Silica Nanoparticles with Radioarsenic.
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. 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.
Department of Medical Physics and ‡Department of Radiology, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin 53726, United States.|Materials Science Program and ∥Carbone Cancer Center, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
Paul A
http://orcid.org/0000-0002-8379-7419
PA
Ellison
Department of Medical Physics and ‡Department of Radiology, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin 53726, United States.|Materials Science Program and ∥Carbone Cancer Center, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
Feng
F
Chen
Department of Medical Physics and ‡Department of Radiology, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin 53726, United States.|Materials Science Program and ∥Carbone Cancer Center, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
Shreya
S
Goel
Department of Medical Physics and ‡Department of Radiology, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin 53726, United States.|Materials Science Program and ∥Carbone Cancer Center, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
Todd E
TE
Barnhart
Department of Medical Physics and ‡Department of Radiology, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin 53726, United States.|Materials Science Program and ∥Carbone Cancer Center, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
Robert J
RJ
Nickles
Department of Medical Physics and ‡Department of Radiology, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin 53726, United States.|Materials Science Program and ∥Carbone Cancer Center, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
Onofre T
OT
DeJesus
Department of Medical Physics and ‡Department of Radiology, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin 53726, United States.|Materials Science Program and ∥Carbone Cancer Center, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
Weibo
W
Cai
D000818:Animals; D016503:Drug Delivery Systems; D051379:Mice; D053758:Nanoparticles; D016062:Porosity; D012822:Silicon Dioxide; D000068936:Theranostic Nanomedicine; D014018:Tissue Distribution
D012822:Silicon Dioxide
As-72; As-76; As-77; arsenic trioxide; image-guided drug delivery; positron emission tomography; radioarsenic; radiolabeling