Chlorin e6 Conjugated Poly(dopamine) Nanospheres as PDT/PTT Dual-Modal Therapeutic Agents for Enhanced Cancer Therapy

ACS Appl Mater Interfaces. 2015 Apr 22;7(15):8176-87. doi: 10.1021/acsami.5b01027. Epub 2015 Apr 10.

Abstract

Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

Keywords: Chlorin e6 (Ce6); cancer therapy; photodynamic therapy (PDT); photothermal therapy (PTT); poly(dopamine) nanoparticles (PDA NPs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chlorophyllides
  • Combined Modality Therapy / methods
  • Diffusion
  • Hep G2 Cells
  • Humans
  • Hyperthermia, Induced / methods*
  • Indoles / chemistry
  • Indoles / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoconjugates / administration & dosage*
  • Nanoconjugates / chemistry
  • Nanospheres / administration & dosage*
  • Nanospheres / chemistry
  • Photochemotherapy / methods*
  • Photosensitizing Agents / therapeutic use
  • Polymers / chemistry
  • Polymers / therapeutic use*
  • Porphyrins / therapeutic use*

Substances

  • Chlorophyllides
  • Indoles
  • Nanoconjugates
  • Photosensitizing Agents
  • Polymers
  • Porphyrins
  • polydopamine
  • phytochlorin