Abstract
Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64Cu2+ and trivalent cation 44Sc3+ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89Zr4+ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.
Highlights
Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent and attracted tremendous interest in the past decades
Mg2Al-LDH nanoparticles were synthesized via quick precipitation and subsequent hydrothermal treatment as reported previously[1,18,19]
Dynamic light scattering (DLS) measurement showed that LDH nanoparticles have an average size of 110 nm in water and 380 nm (PDI: 0.44) in culture media (Fig. 1d)
Summary
Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent and attracted tremendous interest in the past decades. Due to its unique structure and properties, such as rich surface functionality, excellent biocompatibility, wide availability and controllable ion-exchange, LDH exhibits great potential as a delivery agent for biomedical applications[3]. Chelator-free labeling, which eliminates the need of coordination with chelators, has been considered as a promising labeling approach to nanoparticle-based PET imaging[16]. We hypothesized that different radionuclides could be incorporated into LDH nanoparticles through a chelator-free manner, providing a novel nanoplatform for versatile radiolabeling. In this study, we propose chelator-free labeling of BSA-modified Mg2Al-LDH nanoparticles by mixing with a variety of PET isotopes (e.g. 64Cu, 44Sc and 89Zr), followed by evaluation of the labeling yield and stability in vitro. Rapid and persistent tumor uptake via passive targeting was observed in subcutaneous 4T1 murine breast cancer models
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