Magnetic Targeting of mTHPC to Improve the Selectivity and Efficiency of Photodynamic Therapy

Elina Haimov-Talmoud, Yifat Harel, Hadas Schori, Menachem Motiei, Ayelet Atkins, Rachela Popovtzer, Jean Paul Lellouche, Orit Shefi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Photodynamic therapy (PDT) is a promising recognized treatment for cancer. To date, PDT drugs are injected systemically, and the tumor area is irradiated to induce cell death. Current clinical protocols have several drawbacks, including limited accessibility to solid tumors and insufficient selectivity of drugs. Herein, we propose an alternative approach to improve PDT effectiveness by magnetic targeting of responsive carriers conjugated to the PDT drug. We coordinatively attached a meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer to Ce-doped-γ-Fe2O3 maghemite nanoparticles (MNPs). These MNPs are superparamagnetic and biocompatible, and the resulting mTHPC-MNPs nanocomposites are stable in aqueous suspensions. MDA-MB231 (human breast cancer) cells incubated with the mTHPC-MNPs showed high uptake and high death rates in cell population after PDT. The exposure to external magnetic forces during the incubation period directed the nanocomposites to selected sites enhancing drug accumulation that was double that of cells with no magnetic exposure. Next, breast cancer tumors were induced subcutaneously in mice and treated magnetically. In vivo results showed accelerated drug accumulation in tumors of mice injected with mTHPC-MNP nanocomposites, compared to the free drug. PDT irradiation led to a decrease in tumor size of both groups, whereas treatment with the focused magnetic nanocomposites led to significant tumor regression. Our results demonstrate a method to improve the current PDT treatments by applying magnetic forces to effectively direct the drug to cancerous tissue. This approach leads to a highly localized and effective PDT process, opening new directions for clinical PDT protocols.

Original languageEnglish
Pages (from-to)45368-45380
Number of pages13
JournalACS applied materials & interfaces
Volume11
Issue number49
DOIs
StatePublished - 11 Dec 2019

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.

Funding

We wish to thank Dr. Ronen Yehuda from the Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, for his assistance with the in vivo imaging by Maestro II. We thank the Bar-Ilan Institute of Nanotechnology and Advanced Materials for the use of its facilities. O.S. thanks the Israel Science Foundation grant for equipment #2312/18 and the Ministry of Science and Technology for partial support (#3-15629).

FundersFunder number
O.S.
Israel Science Foundation2312/18
Ministry of science and technology, Israel3-15629

    Keywords

    • drug delivery
    • maghemite nanoparticles
    • magnetic targeting
    • photodynamic therapy
    • singlet oxygen

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