Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer

Sean Marrache, Joshua H. Choi, Smanla Tundup, Dhillon Zaver, Donald A. Harn, Shanta Dhar

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)215-223
Number of pages9
JournalIntegrative Biology (United Kingdom)
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

Immunologic Adjuvants
Nanoparticles
Photodynamic therapy
Photosensitizing Agents
Breast Neoplasms
glycolic acid
Photochemotherapy
Cells
Immune system
Single-Stranded DNA
Therapeutics
Cytotoxicity
Drug delivery
Gold
Pharmaceutical Preparations
Polyethylene glycols
Tumors
Polymers
Bone
Irradiation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer. / Marrache, Sean; Choi, Joshua H.; Tundup, Smanla; Zaver, Dhillon; Harn, Donald A.; Dhar, Shanta.

In: Integrative Biology (United Kingdom), Vol. 5, No. 1, 01.01.2013, p. 215-223.

Research output: Contribution to journalArticle

Marrache, Sean ; Choi, Joshua H. ; Tundup, Smanla ; Zaver, Dhillon ; Harn, Donald A. ; Dhar, Shanta. / Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer. In: Integrative Biology (United Kingdom). 2013 ; Vol. 5, No. 1. pp. 215-223.
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