The Novel DPP-BDT Nanoparticles as Efficient Photoacoustic Imaging and Positron Emission Tomography Agents in Living Mice

Int J Nanomedicine. 2020 Jul 14:15:5017-5026. doi: 10.2147/IJN.S238679. eCollection 2020.

Abstract

Background: Molecular imaging is of great benefit to early disease diagnosis and timely treatment. One of the most striking innovations is the development of multimodal molecular imaging technology, which integrates two or more imaging modalities, largely in view of making the best of the advantages of each modality while overcoming their respective shortcomings. Hence, engineering a versatile and easily prepared nanomaterial with integrating multimodal molecular imaging function holds great promise, but is still a great challenge.

Materials and methods: We firstly designed and synthesized a BDT-DPP conjugated polymer and then noncovalent self-assembly with phospholipid-polyethylene glycol endowed BDT-DPP with water solubility and biocompatibility. Followed by [Cu] labeling, the acquired multifunctional nanoparticles (NPs) were studied in detail for the photophysical property. The cytotoxicity and biocompatibility of DPP-BDT NPs were examined through MTT assay and H&E stained analysis. In addition, we investigated the accumulation of the NPs in HepG2 tumor models by positron emission tomography (PET) and photoacoustic (PA) dual-mode imaging.

Results and discussion: The DPP-BDT NPs exhibited excellent optical stability, strong near-infrared (NIR) light absorption as well as fine biocompatibility. After tail vein injection into the living mice, the PA signals in the neoplastic tissues were gradually increased and reached to the maximum at the 4-h post-injection, which was consistent with the PET analysis. Such strong PA and PET signals were attributed to the efficient NPs accumulation resulting from the enhanced permeability and retention (EPR) effect.

Conclusion: The biocompatible DPP-BDT NPs demonstrated to be strong NIR absorption property and PAI sensitivity. Besides, these novel DPP-BDT NPs can act not only as a PA imaging contrast agent but also as an imaging agent for PET.

Keywords: conjugated polymer; nanoparticles; photoacoustic imaging; positron emission tomography imaging.

MeSH terms

  • Animals
  • Contrast Media / chemistry
  • Copper Radioisotopes / administration & dosage
  • Copper Radioisotopes / pharmacokinetics
  • Female
  • Hep G2 Cells
  • Humans
  • Injections
  • Ketones / chemistry*
  • Mice
  • Mice, Nude
  • Multimodal Imaging / methods
  • NIH 3T3 Cells
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Neoplasms, Experimental / diagnostic imaging*
  • Phosphatidylethanolamines / chemistry
  • Photoacoustic Techniques / methods*
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry
  • Positron-Emission Tomography / methods*
  • Pyrroles / chemistry*
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Contrast Media
  • Copper Radioisotopes
  • Copper-60
  • Ketones
  • Phosphatidylethanolamines
  • Polymers
  • Pyrroles
  • Radiopharmaceuticals
  • diketopyrrolopyrrole dye
  • 1,2-distearoylphosphatidylethanolamine
  • Polyethylene Glycols

Grants and funding

This work has been financially supported by the National Natural Science Foundation of China (Nos. 81571747 and 81771907), Science and technology innovation team project of Shanxi Province (No. 201705D131026), Engineering Technology Research Center of Shanxi Province (No. 201805D121008), Scientific and Technological Achievements Transformation Project of Shanxi Province (No. 201704D131006), Laboratory Construction Project of Shanxi Province, and the Projects for Local Science and Technology Development Guided by the Central Committee (No. YDZX20191400002537). The Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province, Support from Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (STIP), Start up Foundation for Doctors of Shanxi Medical University (No. 03201531), and The Youth Research Fund of Shanxi Medical University (02201618) are also acknowledged.