Engineered Cell-Assisted Photoactive Nanoparticle Delivery for Image-Guided Synergistic Photodynamic/Photothermal Therapy of Cancer

ACS Appl Mater Interfaces. 2019 Apr 17;11(15):13935-13944. doi: 10.1021/acsami.9b00022. Epub 2019 Apr 4.

Abstract

Photoactivated therapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a spatiotemporally precise, controllable, and noninvasive method for tumor therapy and has therefore attracted increasing attention in recent years. However, it is still a challenge to obtain highly efficient therapeutic photoactive agents (PAAs) and deliver them into tumor, especially the core of solid tumors. Here, we have developed a newly engineered monocyte (MNC)-based PAA system that realizes precise and highly efficient tumor diagnosis and therapy. First, a near-infrared emissive PAA molecule with both strong singlet oxygen (1O2) production and high photothermal conversion efficiency was precisely designed for realizing simultaneous PDT and PTT of tumor and was further fabricated to form PAA nanoparticles (NPs). After loading the PAA NPs into MNCs, the MNCs were then decorated with cyclic Arg-Gly-Asp (cRGD) groups through a metabolic labeling method to further improve their ability of targeting and homing into the deep regions of tumors. Using this strategy, we have achieved highly efficient solid tumor ablation results both in vitro and in vivo, indicating that our strategy has a promising prospect for solid tumor therapy.

Keywords: cell surface engineering; immune cell-mediated drug delivery; metabolic labeling; photoactivated therapy; synergistic therapy of cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Humans
  • Ketones / chemistry
  • Lasers*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Monocytes / chemistry*
  • Monocytes / cytology
  • Monocytes / metabolism
  • Nanoparticles / chemistry*
  • Neoplasms / diagnosis
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Oligopeptides / chemistry
  • Peptides, Cyclic / chemistry
  • Photochemotherapy
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / therapeutic use
  • Phototherapy
  • Pyrroles / chemistry
  • Quantum Theory
  • Singlet Oxygen / metabolism
  • Transplantation, Heterologous

Substances

  • Ketones
  • Oligopeptides
  • Peptides, Cyclic
  • Photosensitizing Agents
  • Pyrroles
  • diketopyrrolopyrrole dye
  • Singlet Oxygen
  • arginyl-glycyl-aspartic acid