Jump to main content
Jump to site search

Issue 1, 2013
Previous Article Next Article

Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer

Author affiliations

Abstract

A therapeutic technology that combines the phototoxic and immune-stimulating ability of photodynamic therapy (PDT) with the widespread effectiveness of the immune system can be very promising to treat metastatic breast cancer. We speculated that the knowledge of molecular mechanisms of existing multi-component therapies could provide clues to aid the discovery of new combinations of an immunostimulant with a photosensitizer (PS) using a nanoparticle (NP) delivery platform. Therapeutic challenges when administering therapeutic combinations include the choice of dosages to reduce side effects, the definitive delivery of the correct drug ratio, and exposure to the targets of interest. These factors are very difficult to achieve when drugs are individually administered. By combining controlled release polymer-based NP drug delivery approaches, we were able to differentially deliver zinc phthalocyanine (ZnPc) based PS to metastatic breast cancer cells along with CpG-ODN, a single-stranded DNA that is a known immunostimulant to manage the distant tumors in a temporally regulated manner. We encapsulated ZnPc which is a long-wavelength absorbing PS within a polymeric NP core made up of poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG). After coating the outside of the polymeric core with gold NPs (AuNPs), we further modified the AuNP surface with CpG-ODN. In vitro cytotoxicity using 4T1 metastatic mouse breast carcinoma cells shows significant photocytotoxicity of the hybrid NPs containing both ZnPc and CpG-ODN after irradiation with a 660 nm LASER light and this activity was remarkably better than either treatment alone. Treatment of mouse bone marrow derived dendritic cells with the PDT-killed 4T1 cell lysate shows that the combination of PDT with a synergistic immunostimulant in a single NP system results in significant immune response, which can be used for the treatment of metastatic cancer.

Graphical abstract: Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer

Back to tab navigation

Supplementary files

Publication details

The article was received on 16 May 2012, accepted on 26 Jun 2012 and first published on 26 Jul 2012


Article type: Paper
DOI: 10.1039/C2IB20125A
Citation: Integr. Biol., 2013,5, 215-223
  •   Request permissions

    Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer

    S. Marrache, J. H. Choi, S. Tundup, D. Zaver, D. A. Harn and S. Dhar, Integr. Biol., 2013, 5, 215
    DOI: 10.1039/C2IB20125A

Search articles by author

Spotlight

Advertisements