Doxorubicin-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers for NIR-triggered photodynamic therapy and enhanced chemotherapy in drug-resistant breast cancers

Biomaterials. 2015 Jul:57:93-106. doi: 10.1016/j.biomaterials.2015.04.006. Epub 2015 Apr 24.

Abstract

The combination therapy has exhibited important potential for the treatment of cancers, especially for drug-resistant cancers. In this report, bi-functional nanoprobes based on doxorubicin (DOX)-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers (FA-NPs-DOX) were synthesized for in vivo near infrared (NIR)-triggered inorganic photodynamic therapy (PDT) and enhanced chemotherapy to overcome the multidrug resistance (MDR) in breast cancers. Using the up-conversion luminescence (UCL) performance of NaYF4:Yb/Tm converting near-infrared (NIR) into ultraviolent (UV) lights, reactive oxygen species (ROS) were triggered from TiO2 inorganic photosensitizers for PDT under the irradiation of a 980 nm laser, by which the deep-penetration and low photo-damage could be reached. Moreover, nanocarrier delivery and folic acid (FA) targeting promoted the cellular uptake, and accelerated the release of DOX in drug-sensitive MCF-7 and resistant MCF-7/ADR cells. The toxicity assessment in vitro and in vivo revealed the good biocompatibility of the as-prepared FA-NPs-DOX nanocomposites. By the combination of enhanced chemotherapy and NIR-triggered inorganic PDT, the viability of MCF-7/ADR cells could decrease by 53.5%, and the inhibition rate of MCF-7/ADR tumors could increase up to 90.33%, compared with free DOX. Therefore, the MDR of breast cancers could be obviously overcome by enhanced chemotherapy and NIR-triggered inorganic PDT of FA-NPs-DOX nanocomposites under the excitation of a 980 nm laser.

Keywords: Breast cancers; Enhanced chemotherapy; Multidrug resistance; NIR-triggered photodynamic therapy; NaYF(4):Yb/Tm–TiO(2) inorganic photosensitizers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Breast / drug effects*
  • Breast / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use*
  • Drug Resistance, Neoplasm
  • Female
  • Fluorides / pharmacokinetics
  • Fluorides / therapeutic use*
  • Humans
  • Infrared Rays
  • MCF-7 Cells
  • Mice, Nude
  • Nanocomposites / therapeutic use
  • Nanocomposites / ultrastructure
  • Photochemotherapy
  • Photosensitizing Agents / pharmacokinetics
  • Photosensitizing Agents / therapeutic use*
  • Thulium / pharmacokinetics
  • Thulium / therapeutic use
  • Titanium / therapeutic use*
  • Ytterbium / pharmacokinetics
  • Ytterbium / therapeutic use
  • Yttrium / pharmacokinetics
  • Yttrium / therapeutic use*

Substances

  • Antineoplastic Agents
  • Photosensitizing Agents
  • sodium yttriumtetrafluoride
  • titanium dioxide
  • Yttrium
  • Doxorubicin
  • Thulium
  • Titanium
  • Ytterbium
  • Fluorides