Dual Imaging-Guided Oxidative–Photothermal Combination Anticancer Therapeutics

Heme oxygenase-1 (HO-1) is a stress-response protein with potent cytoprotective and antioxidant activity, and its expression in cancer cells is enhanced in response to chemotherapy and radiotherapy. HO-1 is known to serve as a shield to protect cancer cells from anticancer therapy and attenuate apop...

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Published inACS applied materials & interfaces Vol. 10; no. 47; pp. 40424 - 40433
Main Authors Noh, Joungyoun, Jung, Eunkyeong, Yoo, Donghyuck, Kang, Changsun, Kim, Chunho, Park, Sangjun, Khang, Gilson, Lee, Dongwon
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 28.11.2018
Subjects
A549 Cells
Animals
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Heme Oxygenase-1 - metabolism
Humans
Hyperthermia, Induced
Imaging, Three-Dimensional
Lasers
Mice, Nude
Nanoparticles - chemistry
Oxidation-Reduction
Phototherapy
Protoporphyrins - pharmacology
Spectroscopy, Near-Infrared
combination therapy
cancer
heme oxygenase-1
imaging
photothermal therapy
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Summary:Heme oxygenase-1 (HO-1) is a stress-response protein with potent cytoprotective and antioxidant activity, and its expression in cancer cells is enhanced in response to chemotherapy and radiotherapy. HO-1 is known to serve as a shield to protect cancer cells from anticancer therapy and attenuate apoptotic signals. It can be therefore reasoned that inhibition of HO-1 reduces the antioxidant level, making cancer cells more sensitive to photothermal heating. In this work, we developed dual imaging-guided oxidative–photothermal combination nanotherapeutics (OPCN) consisting of amphiphilic polymers conjugated with zinc protoporphyrin as a HO-1 inhibitor and fluorescent IR820 as a photothermal agent. A combination of OPCN and near-infrared (NIR) laser irradiation markedly increased the temperature and exerted significant toxicity through induction of apoptosis. In a mouse model of xenografts, tumors were identified by the strong fluorescence and photoacoustic signals. OPCN combined with NIR laser irradiation resulted in effective and complete thermal ablation of tumors without discernable side effects and tumor recurrence. We believe that OPCN hold tremendous translational potential for dual imaging-guided oxidative–photothermal combination anticancer therapy.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.8b14968