In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled Mesoporous Silica Nanoparticles

Abstract

Traditional chelator-based radio-labeled nanoparticles and positron emission tomography (PET) imaging are playing vital roles in the field of nano-oncology. However, their long-term in vivo integrity and potential mismatch of the biodistribution patterns between nanoparticles and radio-isotopes are two major concerns for this approach. Here, we present a chelator-free zirconium-89 (89Zr, t1/2 = 78.4 h) labeling of mesoporous silica nanoparticle (MSN) with significantly enhanced in vivo long-term (>20 days) stability. Successful radio-labeling and in vivo stability are demonstrated to be highly dependent on both the concentration and location of deprotonated silanol groups (−Si–O–) from two types of silica nanoparticles investigated. This work reports 89Zr-labeled MSN with a detailed labeling mechanism investigation and long-term stability study. With its attractive radio-stability and the simplicity of chelator-free radio-labeling, 89Zr-MSN offers a novel, simple, and accurate way for studying the in vivo long-term fate and PET image-guided drug delivery of MSN in the near future.

Engineering Intrinsically Zirconium‐89 Radiolabeled Self‐Destructing Mesoporous Silica Nanostructures for In Vivo Biodistribution and Tumor Targeting Studies

“…23 89 Zr has an optimal half-life ( t 1/2 = 78.4 h) and relatively low positron energy (β + avg = 395.5 keV), making it suitable for long term in vivo tracking of nanoparticles, low uptake in the background tissue and optimal dosimetry. 24 For these reasons, 89 Zr based radiopharmaceuticals are being actively translated to the clinic, with several clinical trials underway.…”

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

“…On the one hand, drug solubility and stability can be improved and the circulation time can be prolonged by conjugation with nanovectors, which can also induce the selective transport of drugs to tumor sites based on the enhanced permeability and retention effect [17,18]. Numerous inorganic [19,20] and organic nanocarriers [21,22] have been developed for drug delivery, but their potential hazards to human health and the environment have greatly limited their widespread clinical application [23,24]. In the present study we modified biocompatible GNVs that were previously developed by our group.…”

Radiolabeled Nanoparticles in Nuclear Oncology

“…The conclusion of this study was that 89 Zr-MSN could be a useful tool for tracking the in vivo fate and PET imaging of drug delivery systems [39]. Yet another 89 Zr PET tracer was developed by radiolabeling ultrasmall fluorescent silica nanoparticles (C dots) using two pathways: a chelator-free radiolabeling method and a DFO chelating agent.…”

“…Therefore, these nanoconstructs could unambiguously be considered as a useful tool in RES theranostics [92]. [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]2018 organs, while in the case of oral administration low-dose distribution to most organs was confirmed, indicating absorption of the nanoconstructs [93].…”