A new strategy for accurate targeted diagnosis and treatment of cutaneous malignant melanoma: dual-mode phase-change lipid nanodroplets as ultrasound contrast agents

Int J Nanomedicine. 2019 Sep 2:14:7079-7093. doi: 10.2147/IJN.S207419. eCollection 2019.

Abstract

Background: Currently, effective detection and treatment of cutaneous malignant melanoma (CMM) still face severe challenges. Ultrasound molecular imaging as a noninvasive and easy-to-operate method is expected to bring improvements for tumor detection.

Purpose: The aim of this research is to prepare novel phase-change ultrasound contrast agents, Nds-IR780, which can perform not only dual-mode molecule-targeted imaging but also targeted photothermal therapy for CMM.

Methods: A double emulsion process was used to prepare the Nds-IR780. Then, the entrapment rate and drug loading of IR-780 iodide in Nds-IR780 were detected by high-performance liquid chromatography. The biocompatibility of Nds-IR780 was evaluated by a CCK-8 assay and the characteristics and stability of that were verified through the particle size analyzer, laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). The abilities of dual-mode molecule-targeted imaging and targeted photothermal therapy for Nds-IR780 were confirmed via the in vitro and in vivo experiments.

Results: Nds-IR780 had good size distribution, polydispersity index, stability and biosafety. The in vitro and in vivo experiments confirmed that Nds-IR780 were capable of targeting CMM cells with high affinity (22.4±3.2%) and facilitating dual-mode imaging to detect the primary lesion and sentinel lymph nodes (SLNs) of CMM. Furthermore, the photothermal ablation of CMM mediated by Nds-IR780 was very effective in vivo.

Conclusion: The newly prepared Nds-IR780 were observed to be effective targeted theranostic probe for the precise detection and targeted treatment of CMM.

Keywords: CMM; dual-mode phase-change nanodroplets; targeted accurate diagnosis and treatment.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Cell Line, Tumor
  • Contrast Media / chemistry*
  • Humans
  • Hyperthermia, Induced
  • Indoles / chemistry
  • Lipid Droplets / chemistry*
  • Melanoma / diagnosis*
  • Melanoma / therapy*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Phototherapy
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / therapy*
  • Temperature
  • Theranostic Nanomedicine*
  • Tissue Distribution
  • Tumor Burden
  • Ultrasonics

Substances

  • 2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium
  • Biocompatible Materials
  • Contrast Media
  • Indoles