Cascade-amplifying synergistic effects of chemo-photodynamic therapy using ROS-responsive polymeric nanocarriers

Theranostics. 2018 Apr 18;8(11):2939-2953. doi: 10.7150/thno.24015. eCollection 2018.

Abstract

The simple integration of chemotherapeutic drugs and photosensitizers (PSs) into the same nanocarriers only achieves a combination of chemo-photodynamic therapy but may not confer synergistic effects. The boosted intracellular release of chemotherapeutic drugs during the photodynamic therapy (PDT) process is necessary to achieve a cascade of amplified synergistic therapeutic effects of chemo-photodynamic therapy. Methods: In this study, we explored an innovative hyperbranched polyphosphate (RHPPE) containing a singlet oxygen (SO)-labile crosslinker to boost drug release during the PDT process. The photosensitizer chlorin e6 (Ce6) and doxorubicin (DOX) were simultaneously loaded into RHPPE nanoparticles (denoted as SOHNPCe6/DOX). The therapeutic efficacy of SOHNPCe6/DOX against drug-resistant cancer was evaluated in vitro and in vivo. Results: Under 660-nm light irradiation, SOHNPCe6/DOX can produce SO, which not only induces PDT against cancer but also cleaves the thioketal linkers to destroy the nanoparticles. Subsequently, boosted DOX release can be achieved, activating a chemotherapy cascade to synergistically destroy the remaining tumor cells after the initial round of PDT. Furthermore, SOHNPCe6/DOX also efficiently detected the tumor area by photoacoustic/magnetic resonance bimodal imaging. Under the guidance of bimodal imaging, the laser beam was precisely focused on the tumor areas, and subsequently, SOHNPCe6/DOX realized a cascade of amplified synergistic chemo-photodynamic therapeutic effects. High antitumor efficacy was achieved even in a drug-resistant tumor model. Conclusion: The designed SOHNPCe6/DOX with great biocompatibility is promising for use as a co-delivery carrier for combined chemo-photodynamic therapy, providing an alternative avenue to achieve a cascade of amplified synergistic effects of chemo-photodynamic therapy for cancer treatment.

Keywords: ROS responsive; chemo-photodynamic therapy; drug-resistant cancer; on-demand drug release; synergistic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Line, Tumor
  • Chlorophyllides
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers
  • Drug Delivery Systems
  • Drug Liberation
  • Drug Synergism
  • Humans
  • Nanoparticles
  • Neoplasms / drug therapy*
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Polymers / chemistry
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / pharmacology*
  • Reactive Oxygen Species / chemistry
  • Theranostic Nanomedicine

Substances

  • Antibiotics, Antineoplastic
  • Chlorophyllides
  • Drug Carriers
  • Photosensitizing Agents
  • Polymers
  • Porphyrins
  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • phytochlorin
  • Doxorubicin