Abstract
1017
Objectives: Dopamine-melanin nanoparticles (DMNs) were completely composed of naturally occurring Dopamine-melanin and could be easily produced with a simpler and cost-effective chemical method. DMNs were always used as photothermal therapeutic agent or drug carrier with excellent biocompatibility and safety. For using DMNs as tumor targeting imaging agent. Herein, we tested the chelating ability of DMNs to different types of radionuclides (64Cu, 89Zr, 124I and 177Lu) utilizing their intrinsic chelating function, and tested their stabilities in vitro and in vivo, respectively. Then using folic acid to modify the surface of nanoparticles for tumor-specific PET imaging.
Methods: DMNs were synthesized by the oxidation and self-polymerization of dopamine under alkaline conditions. Then, Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM) and Dynamic Light Scattering (DLS) were used to characterize the morphology of nanoparticles. PEG was used to modified the surface of DMNs for better water-solubility. The labeling methods of metal nuclides 64Cu, 89Zr, 177Lu were different from that of elemental nuclides 124I. The surface of DMNs considered to be composed of dihydroxyindole/indolequinone segments having strong π−π interaction and hydrophilic hydroxyl groups on the benzene rings. The metal nuclides 64Cu, 89Zr, 177Lu could label with DMNs directly by adjusting the pH and temperature of the reaction buffer. And N-Bromo Succinimide (NBS) was used as oxidant to oxidize active dihydroxyindole/indolequinone ring of DMNs for electrophilic substitution reaction labeling 124I. The thiol-modified folic acid was loaded for building tumor targeting probe FA-PEG-DMNs, and then we built human cervical cancer Hela xenograft model for Micro-PET imaging after injection with 124I-FA-PEG-DMNs.
Results: We successfully built round-shaped with particle size of 80 nm dopamine-melanin nanoparticles and tumor targeting probe FA-PEG-DMNs.64Cu, 89Zr, 177Lu and 124I efficiently labeled PEG-DMNs with high labelling yield (≥95%). The stability of probes remains good both in vitro (≥ 90%) and in vivo (≥85%) after 48 h incubation or injection respectively. Their specific activity were over 111Gbq/g. Micro-PET imaging showed that the major organ uptake of 124I labeled FA-PEG-DMNs was liver with a value of 11.32±0.36% ID/g, and the Hela xenograft had obvious uptake at the tumor site with a value of 5.32±0.24% ID/g at 48h.
Conclusions: DMNs can be successfully and efficiently labeled with a variety of long half-life metal and elemental nuclides for tumor-specific PET or SPECT imaging. Combined with the photoacoustic imaging capabilities and photothermal therapy functions of DMNs, it is expected to be used in clinical applications as an integrated multimodal imaging probe for diagnosis and treatment.