Enhanced cellular uptake of near-infrared triggered targeted nanoparticles by cell-penetrating peptide TAT for combined chemo/photothermal/photodynamic therapy

Mater Sci Eng C Mater Biol Appl. 2019 Oct:103:109738. doi: 10.1016/j.msec.2019.109738. Epub 2019 May 9.

Abstract

Recently, the emergence of cell-penetrating peptides (CPPs) like TAT has greatly improved the efficiency of cancer therapy by enhancing cellular uptake of nanomaterials. Here, we designed a near-infrared (NIR) triggered TAT-based targeted nanoplatform (cRGD@TAT-DINPs), which co-delivered anticancer drug doxorubicin (DOX) and biocompatible dye indocyanine green (ICG) to realize combined chemo/photothermal/photodynamic therapy of cancer in vitro. The resulting nanoparticles showed favorable monodispersity and colloidal stability. Impressively, the DOX could be released in a promoted manner once the nanoparticles were exposed to NIR light. Confocal laser scanning microscopy (CLSM) and flow cytometry analysis demonstrated an immensely enhanced cellular accumulation of DOX after the simultaneous introduction of targeted ligand cRGD and CPP TAT. In addition, the obtained nanoparticles exhibited explosive temperature elevation and reactive oxygen species (ROS) generation mediated by encapsulated ICG under NIR irradiation, and in vitro cytotoxicity assay confirmed the cRGD@TAT-DINPs had an increasing cytotoxicity and excellent synergistic inhibition capacity. Thus, TAT-based nanosystems provide a high-efficient drug delivery strategy for optimizing combined therapy efficiency of cancer.

Keywords: Cell-penetrating peptides; Combined therapy; Nanocarriers; Near-infrared light.

MeSH terms

  • A549 Cells
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Cell Line, Tumor
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / pharmacokinetics*
  • Coloring Agents / administration & dosage
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Drug Screening Assays, Antitumor
  • Humans
  • Indocyanine Green / administration & dosage
  • Light
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacokinetics
  • Photochemotherapy / methods
  • Reactive Oxygen Species / metabolism
  • tat Gene Products, Human Immunodeficiency Virus / chemistry
  • tat Gene Products, Human Immunodeficiency Virus / pharmacokinetics*

Substances

  • Antibiotics, Antineoplastic
  • Cell-Penetrating Peptides
  • Coloring Agents
  • Peptides, Cyclic
  • Reactive Oxygen Species
  • cyclic arginine-glycine-aspartic acid peptide
  • tat Gene Products, Human Immunodeficiency Virus
  • Doxorubicin
  • Indocyanine Green