Application of mitochondrially targeted nanoconstructs to neoadjuvant X-ray-induced photodynamic therapy for rectal cancer

Wei Deng*, Kelly J. McKelvey, Anna Guller, Alexey Fayzullin, Jared M. Campbell, Sandhya Clement, Abbas Habibalahi, Zofia Wargocka, Liuen Liang, Chao Shen, Viive Maarika Howell, Alexander Frank Engel, Ewa M. Goldys

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In this work, we brought together two existing clinical techniques used in cancer treatment - X-ray radiation and photodynamic therapy (PDT), whose combination termed X-PDT uniquely allows PDT to be therapeutically effective in deep tissue. To this end, we developed mitochondrially targeted biodegradable polymer poly(lactic-co-glycolic acid) nanocarriers incorporating a photosensitizer verteporfin, ultrasmall (2-5 nm) gold nanoparticles as radiation enhancers, and triphenylphosphonium acting as the mitochondrial targeting moiety. The average size of the nanocarriers was about 160 nm. Upon X-ray radiation our nanocarriers generated cytotoxic amounts of singlet oxygen within the mitochondria, triggering the loss of membrane potential and mitochondria-related apoptosis of cancer cells. Our X-PDT strategy effectively controlled tumor growth with only a fraction of radiotherapy dose (4 Gy) and improved the survival rate of a mouse model bearing colorectal cancer cells. In vivo data indicate that our X-PDT treatment is cytoreductive, antiproliferative, and profibrotic. The nanocarriers induce radiosensitization effectively, which makes it possible to amplify the effects of radiation. A radiation dose of 4 Gy combined with our nanocarriers allows equivalent control of tumor growth as 12 Gy of radiation, but with greatly reduced radiation side effects (significant weight loss and resultant death).

Original languageEnglish
Pages (from-to)715-726
Number of pages12
JournalACS Central Science
Volume6
Issue number5
DOIs
Publication statusPublished - 27 May 2020

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  • Projects

    ARC CoE Nanoscale BioPhotonics (CNBP) (RAAP)

    Piper, J., Goldys, E., Packer, N. & Jin, D.

    20/06/14 → …

    Project: Research

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