Effective phthalocyanines mediated photodynamic therapy with doxorubicin or methotrexate combination therapy at sub-micromolar concentrations in vitro

Safdar Ali; Saleh Muhammad; Ahmat Khurshid; Masroor Ikram; Muhammad Maqsood; Carl Fisher; Judy Cathcart; Lothar Lilge

doi:10.1016/j.pdpdt.2018.02.010

Effective phthalocyanines mediated photodynamic therapy with doxorubicin or methotrexate combination therapy at sub-micromolar concentrations in vitro

Photodiagnosis Photodyn Ther. 2018 Jun:22:51-64. doi: 10.1016/j.pdpdt.2018.02.010. Epub 2018 Feb 21.

Authors

Safdar Ali¹, Saleh Muhammad², Ahmat Khurshid³, Masroor Ikram³, Muhammad Maqsood⁴, Carl Fisher⁵, Judy Cathcart⁶, Lothar Lilge⁷

Affiliations

¹ Department of Physics, University of Swabi, Swabi, Pakistan; Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences, Islamabad, Pakistan; Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON, M5G1L7, Canada.
² Department of Physics, University of Swabi, Swabi, Pakistan.
³ Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences, Islamabad, Pakistan.
⁴ Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences, Islamabad, Pakistan; Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON, M5G1L7, Canada.
⁵ Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G1L7, Canada.
⁶ Advanced Optical Microscopy Facility at University Health Network, 101 College Street, Toronto, ON, M5G1L7, Canada.
⁷ Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON, M5G1L7, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G1L7, Canada. Electronic address: llilge@uhnres.utoronto.ca.

PMID: 29476826
DOI: 10.1016/j.pdpdt.2018.02.010

Abstract

To improve a cancer patient's quality of life, short treatment duration resulting in rapid tumour removal while sparing normal tissue are highly desirable. Photodynamic therapy (PDT) commonly applied in a single treatment, while often effective can be limited at low photosensitizer or light doses. Combination therapies can overcome the efficacy limitations while not increasing treatment-associated morbidity. Here the efficacy of combination therapy comprised of doxorubicin (DOX) or methotrexate (MTX) with Photosens mediated PDT was investigated in three cell lines in vitro, employing multiple incubation sequences. Photosense is a mixture of aluminium phthalocyanines with different sulfonation. The results demonstrated higher synergistic effects when DOX or MTX-mediated chemotherapy preceded PDT light activation by 24 h. MTX is marginally more cytotoxic than DOX, when combined with Photosens (AlPcS_2-4) mediated PDT. While MTX and DOX exposure prior to AlPcS_2-4 incubation may enhance mitochondrial localisation photosensitizer, the simultaneous targeting of DNA, proteins, and lipids of the combination therapies leads to the observed high cytotoxicity at sub μM drug doses.

Keywords: Cancer; Cancer Combination therapy.; Chemotherapy; Combination therapy; Hela; MCL-7; Photodynamic Therapy; Phthalocyanines; RG2.

MeSH terms

Animals
Cell Line, Tumor
Cell Survival
Combined Modality Therapy
Doxorubicin / administration & dosage
Doxorubicin / pharmacology*
Humans
Indoles / administration & dosage
Indoles / pharmacology*
Isoindoles
Methotrexate / administration & dosage
Methotrexate / pharmacology*
Organometallic Compounds / administration & dosage
Organometallic Compounds / pharmacology*
Photochemotherapy / methods*
Photosensitizing Agents / administration & dosage
Photosensitizing Agents / pharmacology*
Rats

Substances

Indoles
Isoindoles
Organometallic Compounds
Photosensitizing Agents
aluminum tetrasulfophthalocyanine
Doxorubicin
phthalocyanine
Methotrexate